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Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.
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Objective To investigate the expression of inflammatory factors and brain-derived neurotro-phic factor(BDNF)in the brain hippocampus of Alzheimer's disease(AD)-like mice caused by amyloid β-protein 25-35(Aβ25-35).Methods A total of 40 six-week-old male Kunming mice were taken to construct an AD-like mouse model using bilateral ventricular injection of Aβ25-35,and were divided into the 0 d,7 d,14 d,and 28 d groups for observation,with 10 mice in each group.The Y-maze and new object recognition assay were used to test the learning and memory functions of the mice.The hematoxylin-eosin(HE)staining was used to observe the neuronal damage in the hippocampal region.Immunohistochemical staining was used to detect the expression levels of phosphorylated-tau(p-tau),CD11b and BDNF in hippocampus.ELISA was used to detect the expression levels of inflammatory factors in hippocampus,including interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF)-α,and real-time quantitative reverse transcription PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of BDNF.Results Aβ25-35 could impair memory and cognitive function in the mice.Compared with the 0 d group,the neuron number in the hippocampal tissue of mice in the 14 d and 28 d groups was significantly reduced(P<0.05),and the optical density values of p-Tau and CD11b,and expression levels of IL-1β and TNF-α in the hippocampal region of mice in the 14 d and 28 d groups were significantly increased(P<0.05).In addition,compared with the 0 d group,the relative expression levels of BDNF mRNA and protein in the hippocampal tissue of mice were sig-nificantly increased in the 7 d group(P<0.05),while the relative expression levels of BDNF mRNA and pro-tein were significantly decreased in the 14 d and 28 d groups(P<0.05).Conclusion Aβ25-35 may increase the expression of TNF-α,IL-1β and p-tau in hippocampal tissue by activating microglia,which in turn impaired the memory and cognitive functions of mice,and the expression level of BDNF in hippocampal tissue showed a first increase and then a decrease in the injury period.
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Objective:To observe the effects of Zhulian stimulant type Ⅰ acupuncture on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB and tissue homogenate cyclic adenosine phosphate (cAMP) in rats with diabetic bladder (DCP); To explore the mechanism of Zhulian stimulant type Ⅰacupuncture on DCP.Methods:Totally 50 SD rats were divided into control group, model group, Western medicine group, ordinary acupuncture group, Zhulian stimulant type Ⅰ acupuncture treatment group (acupuncture treatment group) according to random number table method, with 10 rats in each group. DCP rat model was prepared by intraperitoneal injection of streptozotocin (STZ), except for the control group. The Western medicine group was given mecobalamine for gavage; acupoints of "Zhongji", "Sanyinjiao", "Liechou" and "Taichong" were selected. The ordinary acupuncture group was treated with ordinary acupuncture technique, and the acupuncture treatment group was treated with Zhulian stimulant type Ⅰ acupuncture, 1 time/d, 30 minutes/time. Samples were taken after 4 weeks of treatment. The maximum bladder volume, residual urine volume and wet weight of the bladder were detected. The morphology of rat bladder was observed by HE staining. The expression level of BDNF was detected by immunohistochemistry. The expression of cAMP was detected by Western blot. The level of TrkB was determined by ELISA. Real-time fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expressions of BDNF and cAMP.Results:Compared with model group, maximum bladder volume, residual urine volume and wet weight of bladder in Western medicine group, ordinary acupuncture group and acupuncture treatment group decreased ( P<0.01), and those in Western medicine group and acupuncture treatment group were lower than those in ordinary acupuncture group ( P<0.01). The expressions of BDNF mRNA and protein, cAMP mRNA and protein in Western medicine group, ordinary acupuncture group and acupuncture treatment group increased ( P<0.05), and the level of TrkB increased, and the Western medicine group and acupuncture treatment group were higher than that in ordinary acupuncture group ( P<0.05). Conclusions:Zhuliping stimulant type Ⅰ acupuncture has a protective effect on the bladder function of diabetic rats. The mechanism may be related to the up-regulation of BDNF and mRNA, TrkB, cAMP and mRNA expressions.
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Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.
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Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.
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Objective To explore the value of serum IL-11 in the diagnosis and prognosis evaluation of acute cerebral infarction and its correlation with serum brain-derived neurotrophic factor(BDNF).Methods General clinical data of 102 patients with acute cerebral infarction(cerebral infarction group)and 64 normal controls(normal control group)were collected.According to the 90 d mRS score,the cerebral infarction group was divided into the good prognosis subgroup and the poor prognosis subgroup.Pearson correlation analysis was used to analyze the correlation between serum IL-11 and NIHSS score,cerebral infarction volume and serum BDNF.Logistics regression analysis was used to analyze the influencing factors of cerebral infarction prognosis,and the ROC curve of IL-11 in the diagnosis and prognosis of cerebral infarction was drawn.Results The rate of hypertension and the levels of glycosylated hemoglobin and low-density lipoprotein in the cerebral infarction group were significantly higher than those in the normal control group(all P＜0.05).The age,rate of diabetes,glycosylated hemoglobin level,NIHSS score at admission and cerebral infarction volume in the poor prognosis subgroup were significantly higher than those in the good prognosis subgroup(all P＜0.05).The level of serum IL-11 in the cerebral infarction group was significantly lower than that in the normal control group(t =10.123,P＜0.05).The serum IL-11 level in the poor prognosis subgroup of the cerebral infarction group was significantly lower than that in the good prognosis subgroup(t =7.438,P＜0.05).The expression of serum IL-11 in patients with cerebral infarction was negatively correlated with NIHSS score(r =-0.603,P＜0.001)and cerebral infarction volume(r =-0.681,P＜0.001).Logistics regression analysis showed that IL-11 was a protective factor(OR =0.814,P =0.009),while infarct volume(OR = 2.262,P＜0.001)and NIHSS score(OR =2.107,P =0.006)were risk factors affecting the prognosis of patients with cerebral infarction.When IL-11 was applied to the diagnosis of cerebral infarction,the area under the ROC curve was 0.841,the sensitivity was 91.18%,the specificity was 72.42%,and the cut-off value was 378.47;when IL-11 was applied to the prognostic discrimination of cerebral infarction,the area under the ROC curve was 0.786,the sensitivity was 67.09%,the specificity was 87.93%,and the cut-off value was 310.94.The correlation coefficient between serum IL-11 levels and serum BDNF levels in patients with cerebral infarction was r =0.711,P＜0.001.Conclusions The level of serum IL-11 in patients with cerebral infarction is significantly decreased,and the level of IL-11 in patients with poor prognosis is significantly lower than that in patients with good prognosis.Meanwhile,the level of IL-11 is negatively correlated with the level of serum BDNF,which may be used for the auxiliary diagnosis and prognosis evaluation of cerebral infarction.
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OBJECTIVE:With the increasing aging population,the decline of cognitive ability in older adults has received widespread attention.High-intensity interval training(HIIT)has been applied as an emerging exercise intervention to improve cognitive ability in older adults,but its efficacy is still controversial.This study aimed to investigate the effects of HIIT intervention on cognitive ability in older adults,in order to provide a theoretical basis for its application in improving cognitive ability in older adults. METHODS:Randomized controlled trials regarding the effect of HIIT on cognitive ability in older adults were retrieved from databases including CNKI,WanFang,PubMed,Embase,and Web of Science,from the database inception to November 2022.The Cochrane Collaboration's tool for assessing risk of bias in randomized controlled trials was used to evaluate the methodological quality,and RevMan 5.3 software was used for the Meta-analysis of outcome indicators in the included literature. RESULTS:A total of 8 randomized controlled trials,including 4 high-quality and 4 low-quality studies with 369 participants,were included in the Meta-analysis.Meta-analysis showed that(1)compared with moderate-intensity continuous training(MICT),HIIT could effectively improve the maximal oxygen uptake of older adults[weighted mean difference(WMD)=3.78,95%confidence interval(CI):2.79,4.77,P＜0.000 01].Subgroup analysis showed that with long-term intervention(intervention period≥6 weeks),compared with the MICT group,the HIIT group could significantly improve the executive function[standardized mean difference(SMD)=0.36,95%CI:0.20-0.52,P＜0.000 1)and its sub-function inhibition ability(SMD=0.35,95%CI:0.17-0.52,P＜0.000 1)of older adults.(2)Compared with the control group,the HIIT group could effectively improve the maximal oxygen uptake of older adults(WMD=6.75,95%CI:4.20-9.29,P＜0.000 01),memory(SMD=0.20,95%CI:0.03-0.37,P=0.02),executive function(SMD=0.87,95%CI:0.52-1.22,P＜0.000 01),and its sub-function inhibition ability(SMD=0.89,95%CI:0.46-1.33,P＜0.000 1).Subgroup analysis showed that with long-term intervention(intervention period≥6 weeks),compared with the control group,the HIIT group could effectively improve the executive function(SMD=0.75,95%CI:0.41-1.09,P＜0.000 1),its sub-function inhibition ability(SMD=0.50,95%CI:0.19-0.81,P=0.002),and switching ability(SMD=1.65,95%CI:0.86-2.44,P＜0.000 1).(3)With a single intervention,compared with the control group,the HIIT group could effectively improve the executive function(SMD=1.25,95%CI:0.39-2.11,P=0.004)and its sub-function inhibition ability(SMD=2.40,95%CI:0.87-3.92,P=0.002). CONCLUSION:HIIT can effectively improve the executive function and its sub-function inhibition ability of older adults,but has no improvement effect on memory ability.At the same time,long-term HIIT intervention is superior to MICT in improving aerobic capacity and executive function of older adults.
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Objective To investigate the effect and mechanism of long-term indwelling needle of Baihui acupoint during acupuncture on improving neurological function in ischemic stroke mice through brain-derived neurotrophic factor(BDNF)/tyrosine receptor kinase B(TrkB)pathway.Methods A total of 48 male C57BL/6J mice were randomly divided into sham group 1,model group 1,long-term indwelling needle group 1 and conventional indwelling needle group,with 12 mice in each group.A mouse model of ischemic stroke was established by thread occlusion in the latter 3 groups.From the first day after modeling,long-term and conventional indwelling needle at Baihui acupoint was given to the mice in the corresponding groups for 14 consecutive days.Anoth-er 40 male C57BL/6J mice were also subjected and randomly divided into sham group 2,model group 2,and long-term indwelling needle groups 2 and 3,with 10 mice in each group.After model-ing in the latter 3 groups,100 pl adeno-associated virus was injected by caudal vein before acu-puncture treatment.Modified neurological severity score(mNSS)and escape latency,residence time in the target quadrant,and times of crossing the original platform in water maze test were used to evaluate neural function.Results Decreased mNSS score,shorter residence time in the target quadrant,less times of crossing the original platform,and reduced expression levels of BDNF and TrkB in the ischemic brain tissue,and higher apoptotic rate and elevated level of cleaved Caspase-3 in the ischemic brain tissue were observed in the model group 1 when compared with the sham group 1(P＜0.05).While long-term and conventional indwelling needle could reverse above indicators,with long-term indwelling needle more significant than the conventional method(P＜0.05).The long-term indwelling needle group 3 obtained lower mNSS score,reduced residence time in the target quadrant,lower times of crossing the original platform and decreased levels of BDNF and TrkB in the ischemic brain tissue(P＜0.05),and higher apoptotic rate and elevated level of cleaved Caspase-3 in the ischemic brain tissue than the long-term indwelling nee-dle group 2[(16.41±2.25)％vs(7.59±1.09)％,1.46±0.16 vs 0.94±0.12,P＜0.05].Conclusion Long-term indwelling needle at Baihui acupoint more significantly improves the neurological func-tion in ischemic stroke mice than ordinary indwelling needle treatment.Its molecular mechanism is due to activating the BDNF/TrkB pathway.
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Objective:To evaluate the effect of electroacupuncture on P2X4R-p38 mitogen-activated protein kinase (p38 MAPK)-brain-derived neurotrophic factor (BDNF) signaling pathway in trigeminal ganglion of rats with trigeminal neuralgia.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), and electroacupuncture group (E group). The model was developed by chronic constriction of the infraorbital nerve in anesthetized animals. The infraorbital nerve was only exposed without ligation in group S. Rats received electroacupuncture stimulation at the Baihui and Xiaguan acupoints on the affected side for 20 min after developing the model, with a frequency of 80 Hz, twice a day, for 14 consecutive days in E group. Facial mechanical pain threshold (FMT) was measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model. The rats were sacrificed after the last behavioral testing, and the trigeminal ganglia were taken for examination of histopathological changes of trigeminal ganglion (by HE staining) and for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the FMT was significantly decreased at each time point after developing the model, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased ( P<0.05), the pathological changes of the trigeminal ganglion were obvious in group TN. Compared with group TN, the FMT was significantly increased at each time point after developing the model, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological changes of the trigeminal ganglion were significantly attenuated in group E. Conclusions:The mechanism by which electroacupuncture alleviates trigeminal neuralgia may be related to inhibiting the activity of P2X4R-p38MAPK-BDNF signaling pathway and reducing neuroinflammation in rats.
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The incidence of psycho-cardiological diseases， i.e.， cardiovascular diseases combined with psychological disorders， is increasing year by year. Brain-derived neurotrophic factor （BDNF） plays a role in the pathogenesis of such diseases. According to the theory of collateral diseases， our team innovates the concept of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases and summarizes the concepts of "heart of Qi and collaterals" and "heart of vessels and collaterals". We believe that obstructed collaterals and disturbed mental activity run through the whole course of psycho-cardiological diseases， being the core pathogenesis. BDNF closely related to the core pathogenesis can regulate nerve and vascular inflammation， alleviate oxidative stress， and mediate a variety of signaling pathways， thereby promoting the survival and repair of nerve cells and vascular endothelial cells to regulate emotion and protect the heart. Therefore， BDNF is one of the potential biomarkers for clinical treatment of psycho-cardiological diseases. Collateral obstruction caused by blood stasis is specifically manifested as collateral deficiency， blood stasis， and Qi stagnation in collaterals. It can easily lead to inflammation， free radical generation， and antioxidant system changes in the patients with psycho-cardiological diseases， which can cause oxidative stress damage， affect the BDNF level， and result in mental disorders， such as anxiety and depression. Disturbed mental activity is mainly caused by the disturbance in the heart of Qi and collaterals， which is specifically manifested as the disturbance of the mind and liver soul. It is prone to cause anxiety or depression symptoms， which is closely related to the BDNF-mediated abnormal activation of neural circuits， nerve injury， and inflammation. This article elaborates on the theoretical connotation and pathological mechanism of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases from the perspective of BDNF， aiming to provide new ideas for the prevention and treatment of psycho-cardiological diseases and collateral diseases.
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ObjectiveTo decipher the mechanism of Wenxiao powder in alleviating corticosterone-induced depression-like behaviors in mice. MethodMale ICR mice were randomized into normal， model， paroxetine （20 mg·kg-1）， and low- and high-dose （3.27， 6.54 g·kg-1， respectively） Wenxiao powder groups. The mice in normal and model groups received equal volume of saline. Other groups except the normal group were injected with corticosterone subcutaneously 0.5 h after gavage to induce depression. Mice were tested for depression-like behaviors after drug administration. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the corticosterone content in the serum. Nissl staining was performed to observe the damage of hippocampal neurons. Immunofluorescence staining was employed to observe the expression of double cortin （DCX） in the dentate gyrus （DG） of the hippocampus. Western blot was employed to determine the expression of proteins in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB）/extracellular signal-regulated kinase （ERK）/cAMP-response element-binding protein （CREB） pathway in the hippocampus. ResultCompared with the normal group， the model group showed decreased sucrose preference rate， increased immobility time in the tail suspension test （P<0.01）， and reduced residence time in the central area of the open field and the total movement distance （P<0.05， P<0.01）. In addition， the modeling elevated the corticosterone level in the serum （P<0.01）， decreased the volume and intensified the nuclear staining of hippocampal neurons in the DG area， reduced the expression of DCX in the DG area， and down-regulated the protein levels of BDNF， phosphorylated （p）-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. Compared with the model group， low-dose Wenxiao powder improved the mouse behavivors in the sucrose preference， open field， and tail suspension tests （P<0.05， P<0.01）， and high-dose Wenxiao powder improved the behaviors in the sucrose preference and open field tests （P<0.05， P<0.01）. In addition， Wenxiao powder lowered the serum corticosterone level （P<0.01） and recovered the structure and morphology of neurons with obvious nuclei and presence of Nissl bodies in the DG area of the hippocampus. Moreover， Wenxiao powder at both doses promoted the expression of DCX in the DG area， and high-dose Wenxiao powder up-regulated the protein levels of BDNF， p-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. ConclusionWenxiao powder can alleviate corticosterone-induced depression-like behaviors and promote neurogenesis in mice possibly by activating the BDNF/TrkB/ERK/CREB signaling pathway.
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Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.
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ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.
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ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomly assigned into a control group （n=10） and a modeling group （n=50）. Maternal separation combined with restraint stress was adopted to establish the mouse model of depression， and the modeled mice were randomized into model， Wenyang prescription， Jieyu prescription， Wenyang Jieyu prescription， and fluoxetine groups （n=10） on the weaning day （PD21）. From PD21 to PD111， the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then conducted to evaluate the depression， memory， and learning abilities of mice. Immunohistochemistry （IHC） was employed to measure the atomic absorbance （AA） of postsynaptic density protein 95 （PSD95） in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor （BDNF）， phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B （p-TrkB/TrkB）， phosphorylated protein kinase B/protein kinase B （p-Akt/Akt）， phosphorylated mammalian target of rapamycin/mammalian target of rapamycin （p-mTOR/mTOR）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， synaptophysin （Syn）， and PSD95. ResultCompared with the control group， the modeling decreased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.01）. Furthermore， it decreased the expression of PSD95， increased the neuron apoptosis in the hippocampus （P<0.01）， down-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and up-regulated the protein levels of Bax and Caspase-3 （P<0.05） in the hippocampus. Compared with the model group， Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. Moreover， the drugs increased the expression of PSD95， reduced the neuron apoptosis （P<0.01）， up-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and down-regulated the protein levels of Bax and Caspase-3 （P<0.01）. ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.
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Objective:To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in patients with schizophrenia and its effect on brain-derived neurotrophic factor (BDNF).Methods:A total of 130 patients with negative symptoms of schizophrenia who received treatment at The Third Hospital of Quzhou from March 2021 to March 2023 were included in this randomized controlled study. They were divided into a control group and a study group ( n = 65 per group). Both groups of patients were treated with antipsychotic drugs. Based on this, patients in the study group were treated with high-frequency rTMS, while those in the control group were treated with pseudo-rTMS. After 8 weeks of treatment, Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Negative Symptoms (SANS), and Personal and Social Performance Scale (PSP) scores were evaluated in each group before and after treatment. Serum BDNF levels were compared between the two groups before and after treatment. Adverse reactions were observed during the treatment. Results:After 8 weeks of treatment, the PANSS negative subscale score and SANS score in the study group were (16.45 ± 3.98) points and (35.41 ± 6.29) points, respectively, which were significantly lower than (20.08 ± 4.16) points and (41.76 ± 7.36) points in the control group ( t = -7.46, -6.85, both P < 0.05). PSP score in the study group was (66.85 ± 8.93) points, which was significantly higher than (58.79 ± 8.28) points in the control group ( t = 5.62, P < 0.001). There were no significant differences in PANSS positive subscale score, general psychopathology scale score or total score between the two groups (all P > 0.05). After 8 weeks of treatment, the serum BDNF level in the study group was (12.05 ± 2.13) μg/L, which was significantly higher than (8.86 ± 1.94) μg/L in the control group ( t = 9.73, P < 0.001). There was no significant difference in the incidence of adverse reactions during the treatment period between the two groups ( P > 0.05). Serum BDNF level was negatively correlated with PANSS and SANS scores ( r = -0.81, -0.85, both P < 0.001), while it was positively correlated with PSP score ( r = 0.82, P < 0.001). Conclusion:High-frequency rTMS can effectively alleviate the negative symptoms of schizophrenia, increase the secretion of BDNF, and be highly safe.
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Objective:To explore the effect of Baduanjin on gait parameters and serum nerve growth factor in Parkinson disease (PD) patients with freezing of gait(FOG).Methods:From December 2021 to December 2022, thirty-eight PD patients with FOG who met the inclusion and exclusion criteria were randomly divided into observation group ( n=18) and control group ( n=20) by random number table.The patients in both two groups received 4 weeks of drug therapy combined with basic rehabilitation treatment respectively, and the patients in observation group received additional Baduanjin training.Efficacy was evaluated 1 day before intervention and after 4 weeks of intervention through unified Parkinson's disease rating scale-Ⅱ(UPDRS-Ⅱ) item 14, freezing of gait questionnaire (FOGQ), gait starting time, gait cycle, stride length, dynamic plantar peak pressure and average pressure, while the levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor(GDNF) in peripheral blood of patients were tested.SPSS 23.0 software was used to conduct Chi-square test, paired t-test, independent sample t-test and Mann-Whitney U test. Results:Before treatment, there were no significant differences in score of UPDRS-Ⅱ item 14, FOGQ score, gait starting time, gait cycle, stride length, dynamic planar peak pressure, average pressure, peripheral blood BDNF level and GDNF level between the two groups ( t=-0.542, 0.562, 0.490, 0.674, 0.440, 0.606, -0.835, -0.873, -0.250, all P>0.05). After treatment, compared with the control group, dynamic plantar peak pressure (control group (14.26±3.23) N/cm 2, observation group (11.40±4.13) N/cm 2, t=-2.389, P=0.022) and plantar average pressure (control group (3.34±0.72) N/cm 2, observation group (2.79±0.81) N/cm 2, t=-2.209, P=0.034) of the observation group were significantly decreased (both P<0.05). There were no significant differences in UPDRS-Ⅱ item 14, FOGQ score, gait starting time, gait cycle, stride length, BDNF and GDNF concentrations in peripheral blood between the two groups after treatment (all P>0.05). The difference between pre-treatment and post-treatment of FOGQ score (control group 1.00 (0.00, 1.00) , observation group 2.00 (0.75, 3.00), Z=-2.547, P=0.011), gait starting time (control group -1.04 (-1.86, -0.47)s, observation group -2.34 (-3.41, -1.03) s, Z=-2.280, P=0.023), gait cycle (control group 0.29 (0.08, 0.58)s, observation group 0.35 (0.16, 1.00) s, Z=-2.748, P=0.006), stride length(control group 0.19 (0.14, 0.24) m, observation group 0.26 (0.23, 0.38)m, Z=-1.360, P=0.005), the dynamic plantar peak pressure (control group -4.11 (-5.87, -2.57) N/cm 2, observation group -8.44 (-10.12, -4.81) N/cm 2, Z=-3.333, P=0.001) and average pressure (control group -0.55 (-1.00, -0.03) N/cm 2, observation group -1.11 (-1.51, -0.66) N/cm 2, Z=-2.062, P=0.009) in the observation group were better than those in the control group.After treatment, the BDNF level in peripheral blood in observation group was higher than before treatment( t=-2.315, P=0.033). Conclusion:Baduanjin can improve frozen gait score and gait parameters in PD patients with FOG, which may be related to the increase of peripheral blood BDNF.
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Objective To investigate the effects and mechanisms of icariin on changes in fear memory in post-traumatic stress disorder(PTSD)rats.Methods Thirty male SD rats were used to construct a rat model of single prolonged stress(SPS).The model rats were randomly divided into the SPS,icariin,and icariin + K252a(tyrosine kinase receptor B inhibitor)groups(n= 10 each;another 10 normal rats were used as the control group).The icariin and icariin + K252a groups were administered 20 mg/kg icariin by gavage once per day after SPS,while the control and SPS groups were administered the same dose of normal saline.K252a cells were injected into the lateral ventricles.After 2 weeks,anxiety,depression,and fear memory disorder in rats in each group were detected by the mine experiment,ele-vated cross maze experiment,and conditional fear test.The binding activity of icariin to brain-derived neurotrophic factor(BDNF)and the BDNF and TrkB expressions in the rat amygdala were detected by immunohistochemistry.The relative expressions of BDNF and TrkB pro-teins were detected by Western blotting.The expressions of postsynaptic density protein 95(PSD95)and synaptophysin(SYN)in the rat amygdala were detected using immunofluorescence.Results Icariin showed strong binding to BDNF.Compared with the control group,the times of entering the central area and the percentage of movement distance in the central area in the SPS group and the icariin+K252a group were significantly reduced.The open arm entry(OE)and arm opening time(OT)were significantly reduced,the freezing time and defecation times were significantly increased,and the expressions of the BDNF,TrkB,PSD95,and SYN proteins were significantly reduced(P<0.05).Compared with the SPS group,the icariin group rats had significantly increased times of entering the central area and percentages of movement distance in the central area,significantly increased OE and OT,significantly reduced the time of immobilization and defecation,and significantly increased the expressions of BDNF,TrkB,PSD95,and SYN proteins(P<0.05).Conclusion Icariin effectively alleviated the fear memory impairment induced by SPS in rats.This protective effect is related to BDNF/TrkB signaling pathway activation and upregulated PSD95 and SYN expression.
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SUMMARY OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 μM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.
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Introducción. La disfunción ejecutiva asociada a quimioterapia es un efecto adverso del tratamiento antineoplásico convencional y afecta a un porcentaje considerable de personas. Se ha reportado que la presencia de ciertos polimorfismos en genes relevantes puede causar mayor susceptibilidad a padecerlo. Objetivo. Determinar la relación entre el polimorfismo Val66Met (196 G>A) del gen BDNF y el desarrollo de disfunción ejecutiva en mujeres con cáncer de mama tratadas con quimioterapia. Métodos. Se evaluaron a 73 pacientes mujeres con cáncer de mama para determinar disfunción ejecutiva antes y después de la quimioterapia. La evaluación fue realizada con la prueba INECO Frontal Screening (IFS). Se determinó el genotipo (GG=Val/Val, GA=Val/Met y AA=Met/Met) por PCR y secuenciamiento del gen BDNF. El análisis de asociación se realizó mediante el cálculo del odds ratio (OR). Resultados. El 13,7% (n = 10) de pacientes presentó el alelo A (GA y AA), además obtuvieron puntajes significativamente menores de la prueba IFS comparado con las homocigotas GG (p A) del gen BDNF y el desarrollo de disfunción ejecutiva en pacientes con cáncer de mama tratadas con quimioterapia; sin embargo, las portadoras del alelo A (Met) presentaron puntajes menores en la evaluación cognitiva.
Introduction. Chemotherapy-associated executive dysfunction is an adverse effect of conventional antineoplastic treatment that affects many patients. It has been reported that the presence of specific polymorphisms in key genes can cause a greater susceptibility to develop this condition. Objective. To determine the relationship between the Val66Met polymorphism (196 G>A) of the BDNF gene and the development of executive dysfunction in female patients with breast cancer treated with chemotherapy. Methods. 73 female breast cancer patients were evaluated for executive dysfunction before and after chemotherapy. The evaluation was carried out with the INECO Frontal Screening test (IFS). The genotype (GG=Val/Val, GA=Val/Met and AA=Met/Met) was determined by PCR and sequencing of BDNF gene. Association analysis was performed by calculating the Odds Ratio (OR) and by quantitative comparison. Results. 13.7% (n = 10) of the sample presented the allele A (GA and AA), which obtained significantly lower scores in the IFS test compared to the homozygous GG (p A) polymorphism of the BDNF gene and the development of executive dysfunction in patients with breast cancer treated with chemotherapy. However, patients with the allele A (Met) presented significant lower scores in the cognitive assessment.
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Background: The pathogenesis of schizophrenia has been linked to N-methyl-D-aspartate receptor (NMDAr) inhibition and DAr hyperfunction. Geraniol is a naturally occurring acyclic monoterpene with diverse pharmacological applications. We aimed to assess the effect of geraniol on schizophrenia-like symptoms, vis a vis its modulatory actions on neurochemicals in mice models of psychosis. Methods: In acute studies, male Swiss mice (n=5/group) were intraperitoneally treated with geraniol (25, 50 and 100 mg/kg), risperidone (0.5 mg/kg) or vehicle (10 ml/kg) prior to ketamine (KET) (10 mg/kg)-induced stereotypy and hyperlocomotion. In the chronic studies, mice (n=7/group) were exposed to 14 days interventions (geraniol or risperidone) following a preventive treatment with KET (20 mg/kg) from days 7-14 consecutively. The effects of treatments (e.g., geraniol or risperidone) alone and on KET-induced schizophrenia-like symptoms were investigated on the last day, 24 hours after treatments. Following that, neurochemical and neurotrophic alterations in the brain (striatum, prefrontal cortex, and hippocampus) tissues were investigated. Results: Intoxication with KET was associated with schizophrenia-like symptoms as evidenced by stereotypy behavior and hyperlocomotion. KET further induced hyperlocomotion, behavioral despair, and cognitive impairment in the chronic studies. It altered the levels of dopamine, 5-hydroxytrypamine, glutamic acid decarboxylase (GAD), acetylcholinesterase (AChE), and brain-derived neurotrophic factor (BDNF) in brain tissues. However, GER (50 and 100 mg/kg) administration significantly prevented the brain's insults caused by KET. Conclusions: Altogether, the findings support geraniol's neuroprotective activity while also adding to the body of knowledge that geraniol inhibits schizophrenia-like symptoms via modulation of neurochemical and neurotrophic pathways.