Nelumbo nucifera leaves extract ameliorated scopolamine-induced cognition impairment via enhanced adult hippocampus neurogenesis.

In this presentation, we explored the molecular mechanisms of N. nucifera leaf water extracts (NLWEs) and polyphenol extract (NLPE) on scopolamine-induced cell apoptosis and cognition defects. The administration of NLWE and NLPE did not alter the body weight and serum biomarker rs and significantly ameliorated scopolamine-induced cognition impairment according to Y-maze test analysis. In mice, treatment with scopolamine disrupted normal histoarchitecture in the hippocampus, whereas the administration of NLWE and NLPE reversed the phenomenon. Western blot analysis revealed that scopolamine mitigated the expression of doublecortin (DCX), nestin, and NeuN, and cotreatment with NLWE or NLPE significantly recovered the expression of these proteins. NLWE and NLPE upregulated DCX and NeuN expression in the hippocampus region, as evidenced by immunohistochemical staining analysis of scopolamine-treated mice. NLWE and NLPE obviously elevated brain-derived neurotrophic factor (BDNF) and enhanced its downstream proteins activity. NLWE and NLPE attenuated scopolamine-induced apoptosis by reducing Bax and increased Bcl-2 expression. In addition, scopolamine also triggered apoptosis in human neuroblastoma SH-SY5Y cells whereas co-treatment with NLWE or quercetin-3-glucuronide (Q3G) reversed the phenomenon. NLWE or Q3G enhanced Bcl-2 and reduced Bax expression in the presence of scopolamine in SH-SY5Y cells. NLWE or Q3G recovered the inhibitory effects of scopolamine on neurogenesis and BDNF signals in SH-SY5Y cells. Overall, our results revealed that N. nucifera leaf extracts and Q3G promoted adult hippocampus neurogenesis and prevented apoptosis to mitigate scopolamine-induced cognition dysfunction through the regulation of BDNF signaling pathway.

Impact of Freeze-Drying on Cord Blood (CB), Serum (S), and Platelet-Rich Plasma (CB-PRP) Preparations on Growth Factor Content and In Vitro Cell Wound Healing.

Blood-based preparations are used in clinical practice for the treatment of several eye disorders. The aim of this study is to analyze the effect of freeze-drying blood-based preparations on the levels of growth factors and wound healing behaviors in an in vitro model. Platelet-rich plasma (PRP) and serum (S) preparations from the same Cord Blood (CB) sample, prepared in both fresh frozen (FF) and freeze-dried (FD) forms (and then reconstituted), were analyzed for EGF and BDNF content (ELISA Quantikine kit). The human MIO-M1 glial cell line (Moorfield/Institute of Ophthalmology, London, UK) was incubated with FF and FD products and evaluated for cell migration with scratch-induced wounding (IncuCyte S3 Essen BioScience), proliferation with cyclin A2 and D1 gene expression, and activation with vimentin and GFAP gene expression. The FF and FD forms showed similar concentrations of EGF and BDNF in both the S and PRP preparations. The wound healing assay showed no significant difference between the FF and FD forms for both S and PRP. Additionally, cell migration, proliferation, and activation did not appear to change in the FD forms compared to the FF ones. Our study showed that reconstituted FD products maintained the growth factor concentrations and biological properties of FF products and could be used as a functional treatment option.

The Effects of Deep Brain Stimulation of the Subthalamic Nucleus on Vascular Endothelial Growth Factor, Brain-Derived Neurotrophic Factor, and Glial Cell Line-Derived Neurotrophic Factor in a Rat Model of Parkinson's Disease.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has evolved as a powerful therapeutic alternative for the treatment of Parkinson's disease (PD). Despite its clinical efficacy, the mechanisms of action have remained poorly understood. In addition to the immediate symptomatic effects, long-term neuroprotective effects have been suggested. Those may be mediated through neurotrophic factors (NFs) like vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF). Here, the impact of DBS on the expression of NFs was analysed in a rat model of PD. METHODS: Unilateral 6-hydroxydopamine (6-OHDA) lesioned rats received DBS in the STN using an implantable microstimulation system, sham DBS in the STN, or no electrode placement. Continuous unilateral STN-DBS (current intensity 50 µA, frequency 130 Hz, and pulse width 52 µs) was conducted for 14 days. Rats were then sacrificed and brains shock frozen. Striata and motor cortices were dissected with a cryostat. Levels of VEGF, BDNF, and GDNF were analysed, both by quantitative PCR and colorimetric ELISA. RESULTS: PCR revealed a significant upregulation of only BDNF mRNA in the ipsilateral striata of the DBS group, when compared to the sham-stimulated group. There was no significant increase in VEGF mRNA or GDNF mRNA. ELISA analysis showed augmentations of BDNF, VEGF, as well as GDNF protein in the ipsilateral striata after DBS compared to sham stimulation. In the motor cortex, significant increases after DBS were observed for BDNF only, not for the other 2 NFs. CONCLUSIONS: The upregulation of trophic factors induced by STN-DBS may participate in its long-term therapeutic efficacy and potentially neuroprotective effects.

A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose branch exhibits neurite outgrowth-promoting activity: Novel biological roles of fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus japonicus.

Chondroitin sulfate (CS) is a class of sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide unit composed of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). CS chains are found throughout the pericellular and extracellular spaces and contribute to the formation of functional microenvironments for numerous biological events. However, their structure-function relations remain to be fully characterized. Here, a fucosylated CS (FCS) was isolated from the body wall of the sea cucumber Apostichopus japonicus. Its promotional effects on neurite outgrowth were assessed by using isolated polysaccharides and the chemically synthesized FCS trisaccharide ß-D-GalNAc(4,6-O-disulfate) (1-4)[α-l-fucose (2,4-O-disulfate) (1-3)]-ß-D-GlcA. FCS polysaccharides contained the E-type disaccharide unit GlcA-GalNAc(4,6-O-disulfate) as a CS major backbone structure and carried distinct sulfated fucose branches. Despite their relatively lower abundance of E unit, FCS polysaccharides exhibited neurite outgrowth-promoting activity comparable to squid cartilage-derived CS-E polysaccharides, which are characterized by their predominant E units, suggesting potential roles of the fucose branch in neurite outgrowth. Indeed, the chemically synthesized FCS trisaccharide was as effective as CS-E tetrasaccharide in stimulating neurite elongation in vitro. In conclusion, FCS trisaccharide units with 2,4-O-disulfated fucose branches may provide new insights into understanding the structure-function relations of CS chains.

Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity.

Despite fundamental advances in the research on respiratory syncytial virus (RSV) since its initial identification almost 60 years ago, recurring failures in developing vaccines and pharmacologic strategies effective in controlling the infection have allowed RSV to become a leading cause of global infant morbidity and mortality. Indeed, the burden of this infection on families and health care organizations worldwide continues to escalate and its financial costs are growing. Furthermore, strong epidemiologic evidence indicates that early-life lower respiratory tract infections caused by RSV lead to the development of recurrent wheezing and childhood asthma. While some progress has been made in the identification of reliable biomarkers for RSV bronchiolitis, a "one size fits all" biomarker capable of accurately and consistently predicting disease severity and post-acute outcomes has yet to be discovered. Therefore, it is of great importance on a global scale to identify useful biomarkers for this infection that will allow pediatricians to cost-effectively predict the clinical course of the disease, as well as monitor the efficacy of new therapeutic strategies.

Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression.

Ketamine is a promising alternative to traditional pharmacotherapies for major depressive disorder, treatment-resistant depression, and other psychiatric conditions that heavily contribute to the global disease burden. In contrast to the current standard of care medications for these disorders, ketamine offers rapid onset, enduring clinical efficacy, and unique therapeutic potential for use in acute, psychiatric emergencies. This narrative presents an alternative framework for understanding depression, as mounting evidence supports a neuronal atrophy and synaptic disconnection theory, rather than the prevailing monoamine depletion hypothesis. In this context, we describe ketamine, its enantiomers, and various metabolites in a range of mechanistic actions through multiple converging pathways, including N-methyl-D-aspartate receptor (NMDAR) inhibition and the enhancement of glutamatergic signaling. We describe the disinhibition hypothesis, which posits that ketamine's pharmacological action ultimately results in excitatory cortical disinhibition, causing the release of neurotrophic factors, the most important of which is brain-derived neurotrophic factor (BDNF). BDNF-mediated signaling along with vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) subsequently give rise to the repair of neuro-structural abnormalities in patients with depressive disorders. Ketamine's efficacious amelioration of treatment-resistant depression is revolutionizing psychiatric treatment and opening up fresh vistas for understanding the underlying causes of mental illness.

Serum concentrations of osteoprotegerin, brain-derived nerve factor, angiotensin II, and endothelin-1 in aging dogs.

Background: Gerontology is a major research topic in veterinary medicine; however, there are few reports on changes in biomarker levels in aged dogs. Aim: The purpose of this preliminary study was to evaluate the differences in serum biomarker levels between young (less than 36 months) and old (over 108 months) companion dogs. Methods: We measured the serum concentrations of brain-derived neurotrophic factor (BDNF), osteoprotegerin (OPG), angiotensin II (ANGII), and endothelin-1 (ET-1) in both groups (young: n = 16, 19.8 ± 9.3 months old; old: n = 16, 155.8 ± 22.8 months old). Results: Although the concentrations of BDNF did not differ between the two groups, the OPG, ANGII, and ET-1 levels were significantly higher in the old companion dogs than in the young dogs (p < 0.05). Conclusion: OPG, ANGII, and ET-1 concentrations may increase in dogs during aging.

Can exercise attenuate the negative effects of long COVID syndrome on brain health?

The impetus for many governments globally to treat the novel coronavirus (COVID-19) as an endemic warrant more research into the prevention, and management of long COVID syndrome (LCS). Whilst the data on LCS remains scarce, reports suggest a large proportion of recovered individuals will experience ongoing neuropsychological symptoms, even with mild disease severity. The pathophysiology underlying LCS is multifaceted. Evidence suggests that altered inflammatory, neurotrophic, and neurotransmitter pathways within the brain contribute to neuropsychological symptoms reported following COVID-19. Exercise or regular physical activity has long been shown to have positive effects on brain health and cognition through exerting positive effects on inflammatory markers, neurotransmitters, and neurotropic factors analogous to the neurophysiological pathways proposed to be disrupted by COVID-19 infection. Thus, exercise may serve as an important lifestyle behavior in the management of LCS. In this opinion article, we present the evidence to support the positive role of exercise in the management of cognitive symptom that manifest with LCS and discuss important considerations and interactions with cardiorespiratory and exercise tolerance complications that often present for individuals experiencing LCS. We highlight the need for more research and training of sports medicine practitioners and clinical exercise physiologists in the management of LCS with exercise and call for further research to understand the optimal dose-responses and exercise prescription guidelines for cognitive benefits and minimizing other complications.

A Polymorphism in the BDNF Gene (rs11030101) is Associated With Negative Symptoms in Chinese Han Patients With Schizophrenia.

Objective: This study aimed to investigate the association between brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element binding protein (CREB) gene polymorphisms and schizophrenia. Methods: This study used a case-control design, and diagnoses were made based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. One hundred and thirty-four patients with schizophrenia were recruited from the Third People's Hospital of Zhongshan City from January 2018 to April 2020. Sixty-four healthy controls were recruited from the same region. Genotypes at the BDNF gene single nucleotide polymorphisms rs11030101, rs2030324, and rs6265 and the CREB gene single nucleotide polymorphisms rs6740584 and rs2551640 were determined using a MassARRAY mass spectrometer. Linkage disequilibrium and haplotype analyses were performed, and genotype and allele frequencies were compared between groups. The positive and negative symptom scale (PANSS) was used to evaluate the association between the BDNF and CREB gene polymorphisms and schizophrenic symptoms. Results: There was no significant difference in genotype or allele frequencies for rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 between schizophrenic patients and controls (p > 0.05). In addition, there were no significant differences in rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 genotype frequencies between the two groups in the dominant, recessive, or over-dominant models (p > 0.05). Three loci in the BDNF gene and two loci in the CREB gene were in a state of strong linkage disequilibrium. The frequency of haplotype AAC (rs11030101/rs2030324/rs626), composed of three loci in the BDNF gene, was significantly increased in schizophrenic patients compared with control subjects. There were significant differences in the subscores of PANSSS for negative symptoms, in patients with different rs11030101 genotypes of the BDNF gene (p < 0.05). There was also significant differences in the PANSS scores for the general symptom G12 (judgment and lack of insight) in patients with different rs6265 genotypes of the BDNF gene (p < 0.05). Conclusion: The BDNF gene rs11030101/rs2030324/rs6265 AAC haplotype was potentially associated with an increased risk of schizophrenia. In addition, genotypes at the rs11030101 and rs6265 loci may affect the negative symptoms and general symptoms of schizophrenic patients, respectively.

Serum mBDNF and ProBDNF Expression Levels as Diagnosis Clue for Early Stage Parkinson's Disease.

Parkinson's disease (PD) is one of the most common chronic, progressive, and neurodegenerative diseases characterized clinically by resting tremor, bradykinesia, rigidity, and postural instability. As this disease is usually detected in the later stages, the cure is often delayed, ultimately leading to disability due to the lack of early diagnostic techniques. Therefore, it is of great importance to identify reliable biomarkers with high sensitivity and specificity for the early diagnosis of PD. In this study, we aimed to investigate whether serum expressions of mature brain-derived neurotrophic factor (mBDNF) and proBDNF can serve as biomarkers for the diagnosis of PD at early stage. One hundred and fifty-six patients with limb tremor and/or bradykinesia meeting the inclusion criteria were assigned to either ex-PD group (PD cases) or ex-NPD group (non-PD cases) and then reassigned to either po-PD group (with PD) or po-NPD group (without PD) at 1-year follow-up based on the results of the rediagnoses as performed in accordance with MDS Parkinson's diagnostic criteria. To improve early diagnostic accuracy, grouping (PD group and non-PD group) at initial visit and follow-up was performed differently and independently. Serum mBDNF and proBDNF levels were measured by enzyme-linked immunosorbent assays. The results demonstrated that serum levels of mBDNF and mBDNF/proBDNF were significantly lower in the ex-PD group (19.73 ± 7.31 and 0.09 ± 0.05 ng/ml) as compared with the ex-NPD group (23.47 ± 8.21 and 0.15 ± 0.12 ng/ml) (p < 0.01 for both) and in the po-PD group (19.24 ± 7.20 and 0.09 ± 0.05 ng/ml) as compared with the po-NPD group (25.05 ± 7.67 and 0.16 ± 0.14 ng/ml) (p < 0.01 for both). However, a significantly higher serum level of proBDNF was noted in the ex-PD group (235.49 ± 60.75 ng/ml) as compared with the ex-NPD group (191.75 ± 66.12 ng/ml) (p < 0.01) and in the po-PD group (235.56 ± 60.80 ng/ml) as compared with the po-NPD group (188.42 ± 65.08 ng/ml) (p < 0.01). In conclusion, mBDNF/proBDNF can be used as biomarkers for early stage Parkinson's disease; in addition, mBDNF plus proBDNF has better diagnostic value than mBDNF alone in the diagnosis of PD.

Cerebrospinal fluid replacement solutions promote neuroglia migratory behaviors and spinal explant outgrowth in microfluidic culture.

Disorders of the nervous system (NS) impact millions of adults, worldwide, as a consequence of traumatic injury, genetic illness, or chronic health conditions. Contemporary studies have begun to incorporate neuroglia into emerging NS therapies to harness the regenerative potential of glial-mediated synapses in the brain and spinal cord. However, the role of cerebrospinal fluid (CSF) that surrounds neuroglia and interfaces with their associated synapses remains only partially explored. The flow of CSF within subarachnoid spaces (SAS) circulates essential polypeptides, metabolites, and growth factors that directly impact neural response and recovery via signaling with healthy glia. Despite the availability of artificial CSF solutions used in neurosurgery and NS treatments, tissue engineering projects continue to use cell culture media, such as Neurobasal (NB) and Dulbecco's Modified Eagle Medium (DMEM), for development and characterization of many transplantable cells, matrixes, and integrated cellular systems. The current study examined in vitro behaviors of glial Schwann cells (ShC) and spinal cord explants (SCE) within a CSF replacement solution, Elliott's B Solution (EBS), used widely in the treatment of NS disorders. Our tests used EBS to create defined chemical microenvironments of extracellular factors within a glial line (gLL) microfluidic device, previously described by our group. The gLL is comparable in scale to the in vivo SAS that envelopes endogenous CSF and enables molecular transport via mechanisms of convective diffusion. Our results illustrate that EBS solutions facilitate ShC survival, morphology, and proliferation similar to those measured in traditional DMEM, and additionally support glial chemotactic behaviors in response to brain-derived growth factor (BDNF). Our data indicates that ShC undergo significant chemotaxis toward high and low concentration gradients of BDNF with statistical differences between gradients formed within diluents of EBS and DMEM solutions. Moreover, SCE cultured with EBS solutions facilitated measurement of neurite explant extension commensurate with reported in vivo measurements. This data highlights the translational significance and advantages of incorporating CSF replacement fluids to interrogate cellular behaviors and advance regenerative NS therapies.

Placental neurotrophin levels in gestational diabetes mellitus.

OBJECTIVE: Neurotrophins are known to influence the development and maturation of the feto-placental unit and affect fetal growth trajectories. This study reports the levels of nerve growth factor (NGF) and brain-derived growth factor (BDNF) in the placenta of women with gestational diabetes mellitus (GDM). METHODS: A total number of 60 women with GDM and 70 women without GDM (non-GDM) were included in the study. Placental NGF and BDNF levels were measured using commercially available ELISA kits. RESULTS: Placental NGF levels were lower (p < .05) in women with GDM compared to non-GDM women. Maternal body mass index (BMI), mode of delivery, and the gender of the baby influenced the placental NGF levels. Placental BDNF levels were similar in GDM and non-GDM women. There was an influence of baby gender on the placental BDNF levels while maternal BMI and mode of delivery did not show any effect. In regression models adjusted for maternal age at delivery, gestational age, maternal BMI, mode of delivery, and baby gender, the placental NGF levels in the GDM group were lower (-0.144 pg/ml [95% CI -0.273, 22120.016] p = .028) as compared to the non-GDM group. However, there was no difference in the BDNF levels between the groups. CONCLUSION: This study for the first time demonstrates differential effects on neurotrophic factors such as BDNF and NGF in the placenta in pregnancies complicated by GDM. Alterations in the levels of placental neurotrophins in GDM deliveries may affect placental development and fetal brain growth. This has implications for increased risk for neurodevelopmental pathologies in later life.

Overcoming Resistance to Selective Serotonin Reuptake Inhibitors: Targeting Serotonin, Serotonin-1A Receptors and Adult Neuroplasticity.

Major depressive disorder (MDD) is the most prevalent mental illness contributing to global disease burden. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are the first-line treatment for MDD, but are only fully effective in 30% of patients and require weeks before improvement may be seen. About 30% of SSRI-resistant patients may respond to augmentation or switching to another antidepressant, often selected by trial and error. Hence a better understanding of the causes of SSRI resistance is needed to provide models for optimizing treatment. Since SSRIs enhance 5-HT, in this review we discuss new findings on the circuitry, development and function of the 5-HT system in modulating behavior, and on how 5-HT neuronal activity is regulated. We focus on the 5-HT1A autoreceptor, which controls 5-HT activity, and the 5-HT1A heteroreceptor that mediates 5-HT actions. A series of mice models now implicate increased levels of 5-HT1A autoreceptors in SSRI resistance, and the requirement of hippocampal 5-HT1A heteroreceptor for neurogenic and behavioral response to SSRIs. We also present clinical data that show promise for identifying biomarkers of 5-HT activity, 5-HT1A regulation and regional changes in brain activity in MDD patients that may provide biomarkers for tailored interventions to overcome or bypass resistance to SSRI treatment. We identify a series of potential strategies including inhibiting 5-HT auto-inhibition, stimulating 5-HT1A heteroreceptors, other monoamine systems, or cortical stimulation to overcome SSRI resistance.

Co-transplantation of Epidermal Neural Crest Stem Cells and Olfactory Ensheathing Cells Repairs Sciatic Nerve Defects in Rats.

Cell-based therapy is an alternative strategy to improve outcomes of peripheral nerve injury (PNI). Epidermal neural crest stem cell (EPI-NCSC) is obtained from autologous tissue without immunological rejection, which could expand quickly in vitro and is suitable candidate for cell-based therapy. Olfactory ensheathing cell (OEC) could secrete multiple neurotrophic factors (NTFs), which is often used to repair PNI individually. However, whether the combination of EPI-NCSC and OEC have better effects on PNI repair remains unclear. Here we use EPI-NCSC and OEC co-transplantation in a rat sciatic nerve defect model to ascertain the effects and potential mechanisms of cells co-transplantation on PNI. The effect of EPI-NCSC and OEC co-transplantation on PNI is assessed by using a combination of immunohistochemistry (IHC), electrophysiological recording and neural function test. Co-transplantation of EPI-NCSC and OEC exerts a beneficial effect upon PNI such as better organized structure, nerve function recovery, and lower motoneuron apoptosis. IHC and enzyme-linked immuno sorbent assay (ELISA) further demonstrate that cells co-transplantation may improve PNI via the expression of brain derived growth factor (BDNF) and nerve growth factor (NGF) up-regulated by EPI-NCSC and OEC synergistically. Eventually, the results from this study reveal that EPI-NCSC and OEC co-transplantation effectively repairs PNI through enhancing the level of BDNF and NGF, indicating that cells co-transplantation may serve as a fruitful avenue for PNI in clinic treatment.

S-nitrosoglutathione prevents cognitive impairment through epigenetic reprogramming in ovariectomised mice.

The epigenetic signatures associated with cognitive decline driven by lack of estrogen in post-menopausal state, is not well-understood. The present study is an attempt to unravel the epigenetic mechanisms involved in cognitive impairment preceding ovariectomy in mice and evaluate the protective effects of S-nitrosoglutathione (GSNO). A significant decline in cognitive functions was observed in mice following ovariectomy as assessed by Morris water maze and Novel object recognition test. Administration of GSNO (100 µg/kg body weight, orally) daily for 4 weeks was found to ameliorate cognitive deficits observed in ovariectomised (OVX) mice. The activity of histone acetyl-transferase (HAT) was significantly disrupted in cortex and hippocampus of OVX mice. This was accompanied by increased activity of histone deacetylase (HDAC) and increased levels of HDAC-2, HDAC-3 causing lowered acetylated histone (H)3 levels. Reduced H3 acetylation triggers epigenetic repression of brain derived neurotrophic factor (BDNF) in cortex and hippocampus of OVX mice that may be responsible for neuronal damage and cognitive impairment. GSNO supplementation to OVX mice was able to reinstate HAT(CBP/p300) and HDAC balance through S-nitrosylation. GSNO restored histone acetylation at BDNF promoters (pII, pIV) thereby ameliorating BDNF levels and improving brain morphology and cognition. The study suggests that GSNO improves cognitive function in OVX mice by modulating epigenetic programming.

Neurotrophic Factors: An Overview.

The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons and have since been shown to control a number of aspects of survival, development, and function of neurons in both the central and peripheral nervous systems. Limiting quantities of neurotrophins during development control the numbers of surviving neurons to ensure a match between neurons and the requirement for a suitable density of target innervation. Biological effects of each of the four mammalian neurotrophins are mediated through activation of one or more of the three members of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases (TrkA, TrkB, and TrkC). In addition, all neurotrophins activate the p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor receptor superfamily. Neurotrophin engagement of Trk receptors leads to activation of Ras, phosphatidylinositol 3-kinase, phospholipase C-γ1, and signaling pathways controlled through these proteins, including the mitogen-activated protein kinases. Neurotrophin availability is required into adulthood, where they control synaptic function and plasticity and sustain neuronal cell survival, morphology, and differentiation. This article will provide an overview of neurotrophin biology, their receptors, and signaling pathways.

Combined transplantation of GDAs(BMP) and hr-decorin in spinal cord contusion repair.

Following spinal cord injury, astrocyte proliferation and scar formation are the main factors inhibiting the regeneration and growth of spinal cord axons. Recombinant decorin suppresses inflammatory reactions, inhibits glial scar formation, and promotes axonal growth. Rat models of T8 spinal cord contusion were created with the NYU impactor and these models were subjected to combined transplantation of bone morphogenetic protein-4-induced glial-restricted precursor-derived astrocytes and human recombinant decorin transplantation. At 28 days after spinal cord contusion, double-immunofluorescent histochemistry revealed that combined transplantation inhibited the early inflammatory response in injured rats. Furthermore, brain-derived neurotrophic factor, which was secreted by transplanted cells, protected injured axons. The combined transplantation promoted axonal regeneration and growth of injured motor and sensory neurons by inhibiting astrocyte proliferation and glial scar formation, with astrocytes forming a linear arrangement in the contused spinal cord, thus providing axonal regeneration channels.

Synergistic effect of mesenchymal stem cells infected with recombinant adenovirus expressing human BDNF on erectile function in a rat model of cavernous nerve injury.

PURPOSE: To evaluate the combined role of mescenchymal stem cells (MSCs) infected with recombinant adenoviruses expressing human BDNF (rAd/hBDNF) on the erectile dysfunction in rat with cavernous nerve injury. MATERIALS AND METHODS: Rats divided into 4 groups: control group, bilateral cavernous nerve crushing group (BCNC group), BCNC with MSCs group and BCNC with MSCs infected with rAd/hBDNF group. After 4-week, functional assessment was done. PKH26 and BDNF staining of major pelvic ganglion and masson's trichrome staining of corpus cavernosum were performed. Western blot analysis of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) was done in corpus cavernosum. RESULTS: After 4 weeks, BCNC with MSCs and MSCs infected with rAd/hBDNF groups showed significantly well-preserved erectile function compared with BCNC group. Moreover, the erectile function of MSCs infected with rAd/hBDNF group was significantly well-preserved than BCNC with MSCs group. The smooth muscle of corpus cavernosum was significantly preserved in BCNC with MSCs and MSCs infected with rAd/hBDNF groups compared with BCNC group. More preservation of smooth muscle was observed in rats with MSCs infected with rAd/hBDNF than with MSCs alone. Significant increase expression of eNOS and nNOS was noted in rats with MSCs infected with rAd/hBDNF than with MSCs alone. CONCLUSIONS: The erectile function was more preserved after injection with MSCs infected with rAd/hBDNF in rat with ED caused by cavernous nerve injury. Therefore, the use of MSC infected with rAd/hBDNF may have a better treatment effect on ED cause by cavernous nerve injury.