Kamikihito reduces ß-amyloid25-35-induced axon damage via neurotrophic factors.

The Japanese herbal medicine kamikihito (KKT) is widely used for insomnia, anorexia, anemia, and depression. Recently, the efficacy of KKT against Alzheimer's disease (AD) has been demonstrated in clinical and non-clinical studies. To address the mechanism underlying the effect of KKT on AD, we examined the effects of KKT in ß-amyloid (Aß)25-35-exposed primary cultured neurons. The effects of KKT on Aß25-35-induced neurotoxicity were assessed by immunocytochemical assays and Sholl analysis of neurites, and the influence of KKT on neurotrophic factor (NF) gene expression was examined using RT-PCR analysis. As a result, Aß25-35 exposure attenuated the arborization of neurites of single cultured hippocampal neurons, and KKT treatment for 3 days ameliorated the Aß25-35-induced impairment of tau-positive axon outgrowth. This ameliorative effect of KKT was largely abolished by the Trk inhibitor K252a, and expression of NFs, nerve growth factor (Ngf), brain-derived neurotrophic factor (Bdnf), neurotrophin-3 (NT-3) was significantly increased by KKT. These results indicate that KKT ameliorates axonal atrophy via NFs signaling, providing a mechanistic basis for treatment of AD with KKT.

Tibetan mineral-herbal medicine Zuotai alleviates the depressive-like behaviors in chronic restraint-stressed mice while regulating stress hormone, inflammation and monoamine.

Introduction: Zuotai is an ancient mineral-herbal mixture containing ß-HgS in Tibetan medicine. It is used to treat nervous system diseases, similar to Chinese medicine cinnabar and Indian Ayurveda medicine Rasasindura. However, one of the key problems faced by Zuotai is that its indications are ambiguous. Our previous study found that Zuotai exhibited the activity of ameliorating depressive-like behaviors in a chronic mild stress model. However, due to the inherent limitations of animal models in simulating human disease, clear results often require more than one model for confirmation. Methods: Therefore, another depression model, chronic restraint stressed (CRS) mice, was used to validate the antidepression effect of Zuotai. Prophylactic treatment was conducted for 21 consecutive days while mice were subjected to chronic restraint stress. Results: It was observed that Zuotai and ß-HgS alleviated anhedonia, behavioral despair, stereotype behavior, and reduced exploratory and spontaneous movement in CRS mice. Zuotai and ß-HgS also reversed the increases of stress hormone corticosterone (Cort) in serum and pro-inflammatory cytokines in serum and brain, and increased the serotonin in cortex in CRS mice, with positive dose-effect relationship. The number of Ki67-positive cells in the dentate gyrus and the level of brain-derived neurotrophic factor (BDNF) in the hippocampus were slightly elevated in CRS mice treated with Zuotai; however, there was no statistically significant difference. Although Zuotai increased the total Hg concentration in main organs, the levels remained below those needed to result in observed adverse effect, at least for kidney and liver; and Zuotai showed no observed adverse effect on the brain histopathology, the cell proliferation in dentate gyrus, as well as the hippocampal and cortical organ coefficients. Conclusion: Zuotai exhibited the alleviation of depressive-like behaviors in CRS mice, accompanying with ameliorating stress hormone, peripherical and cerebral inflammation, and monoamine neurotransmitter.

A systematic review and meta-analysis of the omega-3 fatty acids effects on brain-derived neurotrophic factor (BDNF).

BACKGROUND: Omega-3 fatty acids (omega-3 FAs) have attracted the attention of researchers because of their influence on circulatory levels of brain-derived neurotrophic factor (BDNF). Our objective was to review systematically and Meta-analyze randomized controlled trials (RCTs) to assess the effects of omega-3 FAs supplementation on serum BDNF concentration. METHODS: Scopus, PubMed, Web of Science, and Cochrane Library were systematically searched until April 2023. The Cochrane risk of bias assessment tool was utilized to evaluate the quality of the studies. A random-effects model was employed to estimate the overall effect size of BDNF levels, using the Standard Mean Difference (SMD) and a 95% confidence interval (CI). The heterogeneity among the studies was assessed using chi-squared and I2 statistics. RESULTS: A total of 12 studies involving 587 subjects were included. The supplementation of PUFA was found to be associated with a significant increase in serum levels of BNDF in the group receiving the supplements, as compared to the placebo group (SMD: 0.72 pg/mL, 95% CI: 0.28, 1.15; P < 0.001) (I2 = 84.39%, P < 0.001). Sub-group analyses revealed similar findings in trials with fewer than 10 weeks, which utilized both animal (fish oil) and herbal (flaxseed) forms of omega-3 supplements with a high daily dosage of 2000mg. CONCLUSION: The present systematic review and meta-analysis indicate the efficacy of omega-3 FAs in increasing the serum concentration of BDNF. Therefore, omega-3 FAs should be prioritized as agents for increasing BDNF in interventions.

The BDNF mimetic R-13 attenuates TBI pathogenesis using TrkB-related pathways and bioenergetics.

Traumatic brain injury (TBI) is major neurological burden globally, and effective treatments are urgently needed. TBI is characterized by a reduction in energy metabolism and synaptic function that seems a primary cause of neuronal dysfunction. R13, a small drug and BDNF mimetic showed promising results in improving spatial memory and anxiety-like behavior after TBI. Additionally, R13 was found to counteract reductions in molecules associated with BDNF signaling (p-TrkB, p-PI3K, p-AKT), synaptic plasticity (GluR2, PSD95, Synapsin I) as well as bioenergetic components such as mitophagy (SOD, PGC-1α, PINK1, Parkin, BNIP3, and LC3) and real-time mitochondrial respiratory capacity. Behavioral and molecular changes were accompanied by adaptations in functional connectivity assessed using MRI. Results highlight the potential of R13 as a therapeutic agent for TBI and provide valuable insights into the molecular and functional changes associated with this condition.

Network pharmacology and molecular docking prediction, combined with experimental validation to explore the potential mechanism of Qishen Yiqi pills against HF-related cognitive dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishen Yiqi Pills (QSYQ) is a classical herbal formula for treating heart failure (HF) and has potential efficacy in improving cognitive function. The latter is one of the most common complications in patients with HF. However, there is no study on treating HF-related cognitive dysfunction by QSYQ. AIMS OF THE STUDY: The study aims to investigate the effect and mechanism of QSYQ on treating post-HF cognitive dysfunction based on network pharmacology and experimental validation. MATERIALS AND METHODS: Network pharmacology analysis and molecular docking was used to explore endogenous targets of QSYQ in treating cognitive impairment. Ligation of the anterior descending branch of the left coronary artery and sleep deprivation (SD) were used to induce HF-related cognitive dysfunction in rats. The efficacy and potential signal targets of QSYQ were then verified by functional evaluation, pathological staining, and molecular biology experiments. RESULTS: 384 common targets were identified by intersecting QSYQ 'compound targets' and 'cognitive dysfunction' disease targets. KEGG analysis showed these targets were enriched to the cAMP signal, and four marks responsible for regulating the cAMP signal were successfully docked with core compounds of QSYQ. Animal experiments demonstrated that QSYQ significantly ameliorated cardiac function and cognitive function in rats suffering from HF and SD, inhibited the reduction of cAMP and BDNF content, reversed the upregulation of PDE4 and downregulation of CREB, suppressed the loss of neurons, and restored the expression of synaptic protein PSD95 in the hippocampus. CONCLUSION: This study clarified that QSYQ could improve HF-related cognitive dysfunction by modulating cAMP-CREB-BDNF signals. It provides a rich basis for the potential mechanism of QSYQ in the treatment of heart failure with cognitive dysfunction.

Effect of acupuncture in the acute phase of intracerebral hemorrhage on the prognosis and serum BDNF: a randomized controlled trial.

Background: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease, with a high rate of disability. In the literature on Chinese traditional medicine, there is increasing evidence that acupuncture can help hematoma absorption and improve neurological deficits after cerebral hemorrhage. Brain-derived neurotrophic factor (BDNF), one of the most studied neurotrophic factors, is involved in a variety of neurological functions and plays an important role in brain injury recovery. We investigated the effect of acupuncture intervention in the acute phase of ICH on the prognosis and serum BDNF levels of several patient groups. Objective: To investigate the influence of acupuncture on the prognosis and brain-derived neurotrophic factor (BDNF) levels in patients in the acute phase of ICH. Methods: From November 2021 to May 2022, 109 subjects were consecutively enrolled, including patients with ICH, who were randomized into the acupuncture group (AG) and sham acupuncture group (SAG), and a control group (CG). The CG received the same acupuncture intervention as the AG, and the SAG received sham acupuncture, with 14 interventions in each group. The level of consciousness of patients with ICH was assessed and serum BDNF levels were measured in all three groups before the intervention and at 3 weeks after onset, and the level of consciousness and outcomes were assessed at 12 weeks after onset. Results: After the intervention, the level of consciousness of the AG improved significantly (P < 0.05); the BDNF level of only the AG increased significantly (P < 0.05); the changes in Glasgow Coma Scale (GCS) score and BDNF level were significantly greater in the AG than in the SAG (P < 0.05), especially for locomotion (P < 0.05). At 12 weeks post-onset, the AG showed better outcomes and recovery of consciousness than the SAG (P < 0.05).

[Acupuncture combined with repetitive transcranial magnetic stimulation for post-stroke depression: a randomized controlled trial].

OBJECTIVE: To observe the curative effect of Shugan Tiaoshen (soothing liver and regulating mind) acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke depression (PSD), and to explore its mechanism. METHODS: Ninety patients of PSD were randomly divided into an acupuncture+rTMS combination group (30 cases), a rTMS combination group (30 cases, 1 case dropped off) and a western medication group (30 cases, 1 case dropped off). The western medication group was treated with escitalopram oxalate tablets, 10 mg orally each time, once a day; on the basis of the treatment in the western medication group, the rTMS combination group was additionally given rTMS, and the frequency was 20 Hz, 20 min each time, once a day, 5 times a week; on the basis of the treatment in the rTMS combination group, the acupuncture+rTMS combination group was additionally treated with Shugan Tiaoshen acupuncture at Baihui (GV 20), Sishencong (EX-HN 1), Yintang (GV 24+), Shenting (GV 24), etc. for 40 min each time, once a day, weekly 5 times, and each group was treated for 4 weeks. Before and after treatment, the scores of Hamilton depression scale-17 (HAMD-17), Montreal cognitive assessment scale (MoCA), Pittsburgh sleep quality index (PSQI) were observed, and serum levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were detected in each group. RESULTS: After treatment, the HAMD-17 scores in the three groups were lower than those before treatment (P<0.01), and the PSQI scores in the acupuncture+rTMS combination group and the rTMS combination group were lower than those before treatment (P<0.01); the above indexes in the acupuncture+rTMS combination group and the rTMS combination group were lower than those in the western medication group (P<0.05), and the PSQI score in the acupuncture+rTMS combination group was lower than that in the rTMS combination group (P<0.05). After treatment, the MoCA scores and serum BDNF levels in the acupuncture+rTMS combination group and the rTMS combination group were higher than those before treatment (P<0.01), and the serum 5-HT levels in the three groups were higher than those before treatment (P<0.01); and the above indexes in the acupuncture+rTMS combination group and the rTMS combination group were higher than those in the western medication group (P<0.05), and which in the acupuncture+rTMS combination group were higher than those in the rTMS combination group (P<0.05). CONCLUSION: On the basis of western medication escitalopram oxalate, the addition of Shugan Tiaoshen acupuncture combined with rTMS therapy can effectively improve cognitive function and sleep quality in patients with PSD, and the effect is better than that of western medication alone or rTMS combined with western medication. Its mechanism of action may be related to the increase of peripheral serum 5-HT and BDNF levels.

[Analgesic effect and mechanism of electroacupuncture on SNI rats based on microglia-BDNF-neuron signal].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Huantiao" (GB 30) and "Weizhong" (BL 40) on the activation of glial cells, the expression of brain-derived neurotrophic factor (BDNF), excitability and the number of dendritic spines of neurons in the spinal dorsal horn in rats with spared nerve injury (SNI) of sciatic nerve, and to explore the analgesic mechanism of EA on SNI. METHODS: PartⅠ: Sixty SD rats were randomly divided into a sham operation group, a model group, an EA group and a sham EA group, 15 rats in each group. Except the sham operation group, the SNI rat model was established in the remaining groups. The rats in the sham operation group were only treated with incision without damaging the nerve. The rats in the EA group were treated with EA at "Huantiao" (GB 30) and "Weizhong" (BL 40) on the affected side, continuous wave, frequency of 2 Hz, current intensity of 1 mA, 30 minutes each time, once a day, for 14 days. The rats in the sham EA group were treated with EA at points 0.5 cm next to "Huantiao" (GB 30) and "Weizhong" (BL 40) on the affected side; the manipulation, EA parameters and treatment course were the same as the EA group. The latency of thermal foot contraction reflex and the threshold of mechanical foot contraction reflex were detected 1 day before modeling and 3, 7 and 14 days after modeling. Fourteen days after modeling, Western blot was used to detect the protein expressions of ionized binding adapter junction protein 1 (Iba-1), glial fibrillary acidic protein (GFAP), BDNF and c-Fos in the spinal dorsal horn; the expressions of Iba-1 and c-Fos proteins in the spinal dorsal horn were detected by immunofluorescence staining; immunohistochemical method was used to detect the expression of GFAP protein in the spinal dorsal horn; Golgi staining was used to detect the number of dendritic spines in spinal dorsal horn neurons. PartⅡ: Thirty SD rats were randomly divided into a control group, a BDNF group and a BDNF+anti-TrkB group, 10 rats in each group. The control group was treated with intrathecal injection of 10 µL mixture with 1︰1 of 0.9% sodium chloride solution and dimethyl sulfoxide (DMSO); the BDNF group was treated with intrathecal injection of 10 µg rat recombinant BDNF dissolved in 10 µL mixture with 1︰1 of 0.9% sodium chloride solution and DMSO; the BDNF+anti-TrkB group was treated with intrathecal injection of 10 µg rat recombinant BDNF and 30 µg tyrosine kinase receptor B (TrkB) antibody dissolved in 10 µL mixture with 1︰1 of 0.9% sodium chloride solution and DMSO. The threshold of mechanical foot retraction reflex was detected 1 day before intrathecal injection and 1, 3 and 7 days after injection. Seven days after injection, the expression of c-Fos protein in the spinal dorsal horn was detected by Western blot and immunofluorescence staining. RESULTS: PartⅠ: Compared with the sham operation group, 3, 7 and 14 days after modeling, the latency of thermal foot contraction reflex and the threshold of mechanical foot contraction reflex in the model group were decreased (P<0.05); 7 and 14 days after modeling, compared with the model group, the latency of thermal foot contraction reflex and the threshold of mechanical foot contraction reflex in the EA group were increased (P<0.05). The expressions of Iba-1, GFAP, BDNF, c-Fos proteins and the number of neuronal dendritic spines in the spinal dorsal horn in the model group were higher than those in the sham operation group (P<0.05); the expressions of Iba-1, BDNF, c-Fos proteins and the number of neuronal dendritic spines in the EA group were lower than those in the model group (P<0.05). PartⅡ: 3 and 7 days after intrathecal injection, the threshold of mechanical foot retraction reflex in the BDNF group was lower than that in the control group (P<0.05); the threshold of mechanical foot retraction reflex in the BDNF+anti-TrkB group was higher than that in the BDNF group (P<0.05). The expression of c-Fos protein in spinal dorsal horn in the BDNF group was higher than that in the control group (P<0.05); the expression of c-Fos protein in spinal dorsal horn in the BDNF+anti-TrkB group was lower than that in the BDNF group (P<0.05). CONCLUSION: The analgesic effect of EA at "Huantiao" (GB 30) and "Weizhong" (BL 40) on SNI rats may be related to inhibiting the activation of microglia in the dorsal horn of the spinal cord, thereby blocking the signal of microglia-BDNF-neuron, and finally reducing the excitability of neurons.

[Effect of Tongdu Tiaoshen acupuncture on CREB/BDNF/TrkB signaling pathway of hippocampus in rats with post-stroke depression].

OBJECTIVE: To observe the regulative effect of Tongdu Tiaoshen acupuncture on the depression-like behavior and cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tyrosine protein kinase B (TrkB) signaling pathway of hippocampus in rats with post-stroke depression (PSD), and to explore its possible mechanism on improving PSD. METHODS: A total of 36 SPF SD rats were randomized into a sham operation group, a model group and a Tongdu Tiaoshen group, 12 rats in each group. The compound method of Zea Longa suture-occlusion and chronic unpredictable mild stress (CUMS) was used to establish the PSD model in rats of the model group and the Tongdu Tiaoshen group. On the 4th day after modeling, acupuncture was applied at "Dazhui" (GV 14), "Shuigou" (GV 26), "Baihui" (GV 20) and "Shenting" (GV 24) in the Tongdu Tiaoshen group, 40 min every time, once a day, 6 times a week for 4 weeks consecutively. On the 2nd day after PSD modeling and after 4-week intervention, Zea Longa neurobehavioral score was evaluated, sucrose water consumption test and open-field test were performed; biochemical method was used to detect the SOD, CAT activity and MDA level in hippocampal CA1 area; ELISA method was used to detect the serum level of BDNF; real-time PCR was used to detect the mRNA expression of BDNF, TrkB and CREB in hippocampal CA1 area; Western blot was used to detect the protein expression of BDNF, TrkB, CREB and p-CREB in hippocampal CA1 area. RESULTS: Compared with the sham operation group, Zea Longa neurobehavioral scores were increased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were decreased after modeling and intervention in the model group and after modeling in the Tongdu Tiaoshen group (P<0.05). Compared with the model group, Zea Longa neurobehavioral score was decreased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were increased after intervention in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were decreased (P<0.05), MDA level in hippocampal CA1 area was increased in the model group (P<0.05); compared with the model group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were increased (P<0.05), MDA level was decreased in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the mRNA expression of BDNF, TrkB and CREB as well as the protein expression of BDNF, TrkB, CREB and p-CREB were decreased in hippocampal CA1 area in the model group (P<0.05); compared with the model group, the mRNA expression of BDNF, TrkB and CREB, the protein expression of BDNF, TrkB and p-CREB as well as the ratio of p-CREB/CREB were increased in the Tongdu Tiaoshen group (P<0.05). CONCLUSION: Tongdu Tiaoshen acupuncture can improve the depression-like behavior in PSD rats, the mechanism may be related to the inhibition of oxidative stress in hippocampal tissues and the enhanced activity of CREB/BDNF/TrkB signaling pathway.

Effect of Epigallocatechin-3-gallate on Stress-Induced Depression in a Mouse Model: Role of Interleukin-1ß and Brain-Derived Neurotrophic Factor.

Epigallocatechin 3-gallate (EGCG) is a natural polyphenolic antioxidant in green tea leaves with well-known health-promoting properties. However, the influence of EGCG on a chronic animal model of depression remains to be fully investigated, and the details of the molecular and cellular changes are still unclear. Therefore, the present study aimed to investigate the antidepressant effect of EGCG in mice subjected to chronic unpredictable mild stress (CUMS). After eight consecutive weeks of CUMS, the mice were treated with EGCG (200 mg/kg b.w.) by oral gavage for two weeks. A forced swimming test (FST) was used to assess depressive symptoms. EGCG administration significantly alleviated CUMS-induced depression-like behavior in mice. EGCG also effectively decreased serum interleukin-1ß (IL-1ß) and increased the mRNA expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampal CA3 region of CUMS mice. Furthermore, electron microscopic examination of CA3 neurons in CUMS mice showed morphological features of apoptosis, loss or disruption of the myelin sheath, and degenerating synapses. These neuronal injuries were diminished with the administration of EGCG. The treatment effect of EGCG in CUMS-induced behavioral alterations was comparable with that of clomipramine hydrochloride (Anafranil), a tricyclic antidepressant drug. In conclusion, our study demonstrates that the antidepressive action of EGCG involves downregulation of serum IL-1ß, upregulation of BDNF mRNA in the hippocampus, and reduction of CA3 neuronal lesions.

Neuroprotective role of Bacopa monnieri extract in modulating depression in an experimental rat model.

BACKGROUND: Depression is a common illness with no definite treatment. METHODS: The study involved 2 experimental periods; 45-day (P1) followed by 30-day (P2). 40 adult albino rats were randomly divided into 4 groups. Grp 1 received saline orally while Grp 2 reserpine inraperitoneally (ip) during P1 and P2. Grps 3 and 4 received reserpine during P1, followed by reserpine plus B. monnieri, and reserpine plus citalopram ip during P2, respectively. Forced swimming test (FST) was performed at beginning and end of P1 and P2. Animals were sacrificed by end of P2 and brain taken for histopathological examination and ELISA estimation of serotonin, dopamine, norepinephrine, BDNF, MCP-1, FAS, and Bcl-2. RESULTS: During P1, reserpine prolonged immobility time (IT) in FST in Grps 2, 3, and 4. IT was subsequently lowered in Grps 3 and 4 but remained elevated in Grp 2 by end of P2. Serotonin, dopamine and norepinephrine were lowered in Grps 2, 3, and 4, but in Grps 3 and 4, levels were comparable to Grp1. BDNF and Bc1-2 were reduced in Grps 2, 3, and 4, with higher levels in Grps 3 and 4 than Grp 2. MCP-1 and FAS were elevated in Grps 2, 3, and 4, but levels were lower in Grps 3 and 4 than in Grp 2. Histopathology showed congested cerebral cortex in Grp 2 and normal cortex in other groups. LIMITATIONS: Only adult male rats were involved and effects of co-administration of B. monnieri and citalopram were not characterized. CONCLUSION: B. monnieri improves depression comparable to citalopram in reserpine-induced depression.

Vitisin A, a Resveratrol Tetramer, Improves Scopolamine-Induced Impaired Learning and Memory Functions in Amnesiac ICR Mice.

Resveratrol has been reported to exhibit neuroprotective activities in vitro and in vivo. However, little is known about resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B with the same molecular mass in the improvement of degenerative disorders. In this study, two 95% ethanol extracts (95EE) from stem parts of Vitis thunbergii Sieb. & Zucc. (VT-95EE) and from the root (R) parts of Vitis thunbergii var. taiwaniana (VTT-R-95EE) showed comparable acetylcholinesterase (AChE) inhibitory activities. It was found that VT-95EE and VTT-R-95EE showed different distribution patterns of identified resveratrol and resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B based on the analyses of HPLC chromatographic profiles. The hopeaphenol, vitisin A, and vitisin B, showed AChE and monoamine oxidase-B inhibitions in a dose-dependent manner, among which vitisin B and vitisin A exhibited much better activities than those of resveratrol, and had neuroprotective activities against methylglyoxal-induced SH-SY5Y cell deaths. The scopolamine-induced amnesiac ICR mice treated with VT-95EE and its ethyl acetate-partitioned fraction (VT-95EE-EA) at doses of 200 and 400 mg/kg, or vitisin A at a dose of 40 mg/kg, but not vitisin B (40 mg/kg), were shown significantly to improve the impaired learning behaviors by passive avoidance tests compared to those in the control without drug treatments (p < 0.05). Compared to mice in the control group, the brain extracts in the vitisin A-treated mice or donepezil-treated mice showed significant reductions in AChE activities and malondialdehyde levels (p < 0.05), and elevated the reduced protein expressions of brain-derived neurotrophic factor (BDNF) and BDNF receptor, tropomyosin receptor kinase B (TrkB). These results revealed that vitisin A was the active constituent in the VT-95EE and VTT-95EE, and the VT medicinal plant and that the endemic variety of VTT has potential in developing functional foods for an unmet medical need for neurodegenerative disorders.

Electroacupuncture promotes nerve regeneration and functional recovery in rats with spinal cord contusion through the coordinate interaction of CD4 and BDNF.

To explore the effect of electroacupuncture on spinal cord injury (SCI) involving immune-related factors and regeneration-related factors in rats. The model of spinal cord contusion was established by PCI 3000 instrument. Two types of acupuncture points were selected for electroacupuncture treatment on rats. The rats were tested once a week, and the fiber remodeling was detected by magnetic resonance imaging. Transcriptome sequencing was performed on spinal scar samples. Using Python to write code, statistical analysis and bioinformatics analysis of the correlation between transcriptome sequencing data and fiber reconstruction results are carried out. Lastly, the expression of CD4 and brain-derived neurotrophic factor (BDNF) in spinal cord scar was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Electroacupuncture exhibited a positive effect on the recovery of motor function in rats after SCI. Bioinformatics analysis found a direct interaction between CD4 and BDNF. Transcriptome sequencing and PCR results verified that electroacupuncture significantly reduced the expression of CD4, and increased significantly the expression of BDNF, simultaneously corresponding to nerve regeneration in rats with SCI. Our results showed that electroacupuncture intervention in SCI rats improves neural behavior via inhibiting the expression of CD4 and increasing the expression of BDNF.

Brain-Derived Neurotrophic Factor (BDNF) as an Indicator for Effects of Cognitive Behavioral Therapy (CBT): A Systematic Review.

Brain-derived neurotrophic factor (BDNF) is a protein affecting survival of existing neurons and neuronal maturation. Patients suffering from several mental disorders exhibit reduced BDNF levels comparing to healthy population. In this systematic review we aim to evaluate the effect of broadly defined cognitive behavioral therapy (CBT) on BDNF levels in psychiatric patients. A literature search was performed using PubMed and Google Scholar data bases. The resources were searched between 14 January and 3 February 2022. Following the inclusion criteria, a total of 10 randomized-controlled trials were included. The results of our research indicate that BDNF levels might be considered an indicator of a result achieved in psychotherapy of cognitive functions. However, no such correlation was observed for mindfulness-based practices intended to lower stress levels or improve the quality of life. It is important to notice that present research showed no consistent correlation between the increase in BDNF levels and the perceived effectiveness of the procedures. Thus, the exact role of BDNF remains unknown, and so far, it cannot be taken as an objective measure of the quality of the interventions.

Music-Based Intervention Ameliorates Mecp2-Loss-Mediated Sociability Repression in Mice through the Prefrontal Cortex FNDC5/BDNF Pathway.

Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investigate the mechanism by which music-based interventions compromise sociability impairments in mecp2 null/y mice as an experimental RTT model. Male mecp2 null/y mice and wild-type mice (24 days old) were randomly divided into control, noise, and music-based intervention groups. Mice were exposed to music or noise for 6 h/day for 3 consecutive weeks. Behavioral patterns, including anxiety, spontaneous exploration, and sociability, were characterized using open-field and three-chamber tests. BDNF, TrkB receptor motif, and FNDC5 expression in the prefrontal cortex (PFC), hippocampus, basal ganglia, and amygdala were probed using RT-PCR or immunoblotting. mecp2 null/y mice showed less locomotion in an open field than wild-type mice. The social novelty rather than the sociability of these animals increased following a music-based intervention, suggesting that music influenced the mecp2-deletion-induced social interaction repression rather than motor deficit. Mechanically, the loss of BDNF signaling in the prefrontal cortex and hippocampal regions, but not in the basal ganglia and amygdala, was compromised following the music-based intervention in mecp2 null/y mice, whereas TrkB signaling was not significantly changed in either region. FNDC5 expression in the prefrontal cortex region in mecp2 null/y mice also increased following the music-based intervention. Collective evidence reveals that music-based interventions improve mecp2-loss-induced social dysfunction. BDNF and FNDC5 signaling in the prefrontal cortex region mediates the music-based-intervention promotion of social interactions. This study gives new insight into the mechanisms underlying the improvement of social behaviors in mice suffering from experimental Rett syndrome following a music-based intervention.

Neural Fuyuan Formula promotes neural plasticity through BDNF/Trkß signaling pathway.

BACKGROUND: Depression after stroke is usually a chronic process, which was associated with many health problems. This study was aimed to investigate the underline mechanism of the effect of Neural Fuyuan Formula (NFF) in post-stroke depression and the role of brain-derived neurotrophic factor (BDNF) in the signal pathway regulated by NFF. METHODS: A rat post-stroke depression model was established. Synaptic plasticity of rat was detected by Electron microscopy. The expression of BDNF signaling proteins and synapse related proteins were measured by Western blot. The expression of Synapsin-1 (SYN1) in rat and the culture neurons was detected by Western blot and immunofluorescence. Dendritic complexity was also measured. RESULTS: NFF could attenuate the synapse change in the post-stroke depression (PSD) model rat. NFF increased the expression of BDNF signaling proteins and synapse related proteins of the PSD model rat (P&0.05). NFF increased the expression of SYN1 in rat and the culture neurons (P&0.05). NFF could also increase the dendritic complexity in culture neurons (P&0.05). CONCLUSIONS: NFF promoted recovery of neurological function through BDNF signaling pathways, which further affirm the curative effect of NFF for treatment of post-stroke depression.

Low-Dose Ozone Therapy Improves Sleep Quality in Patients with Insomnia and Coronary Heart Disease by Elevating Serum BDNF and GABA.

We studied the effects of low-dose ozone therapy on the sleep quality of patients with coronary heart disease (CHD) and insomnia by measuring the levels of brain-derived neurotrophic factor (BDNF) and GABA in blood serum. The 3-month course of low-dose ozone therapy significantly elevated serum BDNF and GABA in CHD patients with insomnia and improved parameters of anxiety, depression, and sleep quality according to Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), and Self-Rating Scale of Sleep (SRSS). Ozone therapy also significantly (p<0.05) improved the total antioxidant status of the body by elevating catalase activity and reducing malondialdehyde and 8-OHdeoxyguanosine in the saliva. The serum levels of BDNF and GABA negatively and closely correlated with PSQI and HADS scores. Low-dose ozone therapy improved sleep quality and reduced PSQI and HADS scores due to up-regulation of BDNF and GABA.

Influence of progestational stress on BDNF and NMDARs in the hippocampus of male offspring and amelioration by Chaihu Shugan San.

BACKGROUND: Progestational stress has been proven to be a risk for the neural development of offspring, especially in the hippocampus. However, whether Chaihu Shugan San (CSS) can ameliorate hippocampal neural development via the regulation of brain-derived neurotrophic factor (BDNF), and N-methyl-D-aspartate receptors (NMDAR) 2A (NR2A) and 2B (NR2B), and the mechanism of such action remains unclear. METHODS: Thirty-six female rats were randomly allocated into control, chronic immobilization stress (CIS) and CSS groups according to the random number table, respectively. The male offspring were fed for 21 days after birth then randomly divided into the same three groups (6 rats/group) as the female rats. Female rats, except for the control group, underwent 21-day CIS to established a progestational stress anxiety-like model which was evaluated by body weight, the elevated plus-maze (EPM) test and serum dopamine (DA) measured using an enzyme-linked immunosorbent assay (ELISA). The expression levels of estrogen receptors (ERα/ERß) and progesterone receptor (PR) in female rat ovaries were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The hippocampal tissue in the 21-day offspring was observed by hematoxylin-eosin (HE) staining. The concentration of BDNF, NR2A, and NR2B were measured by RT-qPCR and immunohistochemistry in the CA3 and dentate gyrus (DG) regions of offsprings' hippocampus. RESULTS: Compared with the female control group, significant differences in body weight, EPM test and DA concentration were observed in the CIS group, meanwhile, the concentration of ERα (P < 0.05), PR (P < 0.05) and ERß in the ovaries were decreased. In the offsprings' hippocampus of the CIS group, the chromatin of the nucleus was edge set and with condensed and irregular morphology nucleus, and the cytoplasm was unevenly stained with spaces around the cells, moreover, the expression levels of BDNF, NR2A, and NR2B were also declined (P < 0.05). However, Chaihu Shugan San reversed these changes, especially the BDNF in the DG region (P < 0.05), and NR2A and NR2B in the CA3 and DG region (P < 0.05). CONCLUSIONS: CSS could ameliorate the neural development of the hippocampus in offspring damaged by anxiety-like progestational stress in female rats via regulating the expression levels of ERα, ERß, and PR in female rat ovaries and BDNF, NR2A, and NR2B in the hippocampus of their offspring.

Effects of Compound 511 on BDNF-TrkB Signaling in the Mice Ventral Tegmental Area in Morphine-Induced Conditioned Place Preference.

Compound 511 (511) is specially developed for opioid addiction treatment based on the Ancient Chinese drug rehabilitation literature, and its composition has profound effects in the treatment of drug addiction in various clinical trials and animal experiments. The effect of 511 on the rewarding properties of morphine and craving responses and its potential mechanisms remain unclear. Here, we have applied a conditioned place preference (CPP) paradigm in mice to measure morphine-induced rewarding effects under the treatment of 511. Then we used the RNA sequencing strategy to screen its potential mechanisms. In our research, firstly, we found 511 could decrease CPP score, locomotor activity, self-administration, jumping behavior, weight loss, wet-dog shakes, and stereotyped behavior. Then the brain VTA region tissues were performed mRNA sequencing to detect potential mechanisms. We found the brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) were downregulated in morphine-induced CPP, whereas the decreased BDNF and TrkB were reversed after 511 treatment. We retested the levels of BDNF and TrkB using qRT-PCR and Western blot and found the similar results to mRNA sequencing. It has been widely reported that BDNF-TrkB signaling in the VTA is involved in multiple facets of addiction, including reward and motivation, so we focused on the BDNF-TrkB signaling to investigate the anti-addiction mechanisms of 511 in morphine addiction mice. We studied the downstream pathway of BDNF-TrkB and the soma size of dopaminergic neurons. The results showed 511 could increase the phosphorylation levels of PI3K and AKT, which were decreased in morphine-induced CPP. Simultaneously, 511 could decrease the level of PLCγ1 and the phosphorylation levels of ERK and S6K, which were increased in morphine-induced CPP. In addition, 511 also enlarged the soma size of VTA dopaminergic neurons, which was reduced in morphine-induced CPP. Hence, our research indicated 511 maybe mediate the BDNF-TrkB signaling in VTA to improve morphine addiction behavior.

Eucommia Leaf Extract Induces BDNF Production in Rat Hypothalamus and Enhances Lipid Metabolism and Aerobic Glycolysis in Rat Liver.

BACKGROUND: Mutations in the brain-derived neurotrophic factor (BDNF) gene and its receptor, tyrosine receptor kinase B (TrkB), have been reported to cause severe obesity in rodents. Our previous study demonstrated that the oral administration of 5% Eucommia leaf extract (ELE) or ELE aroma treatment (ELE aroma) produced anti-obesity effects. OBJECTIVE: In this study, we investigated the effects of ELE on glycolysis and lipid metabolism in male Sprague-Dawley rats, as well as the effects of ELE on BDNF in rat hypothalamus. METHODS AND RESULTS: A significant reduction and a reduction tendency in the respiratory quotient were observed in association with 5% ELE and ELE aroma treatment, respectively. Furthermore, RT-qPCR results showed significant increases in Cpt2, Acad, Complex II, and Complex V mRNA levels in the liver with both treatments. In addition, in rat hypothalamus, significant elevations in BDNF, Akt, PLCγ proteins and CREB phosphorylation were observed in the 5% ELE group and the ELE aroma group. Furthermore, the Ras protein was significantly increased in the ELE aroma group. On the other hand, significant dephosphorylation of ERK1/2 was observed by the western blotting in the 5% ELE group and the ELE aroma group. CONCLUSION: These findings suggest that the ELE treatment enhances the lipid metabolism and increases the aerobic glycolytic pathway, while ELE-induced BDNF may affect such energy regulation. Therefore, ELE has the possibility to control metabolic syndrome.