Select neurotrophins promote oligodendrocyte progenitor cell process outgrowth in the presence of chondroitin sulfate proteoglycans.

Axonal damage and the subsequent interruption of intact neuronal pathways in the spinal cord are largely responsible for the loss of motor function after injury. Further exacerbating this loss is the demyelination of neighboring uninjured axons. The post-injury environment is hostile to repair, with inflammation, a high expression of chondroitin sulfate proteoglycans (CSPGs) around the glial scar, and myelin breakdown. Numerous studies have demonstrated that treatment with the enzyme chondroitinase ABC (cABC) creates a permissive environment around a spinal lesion that permits axonal regeneration. Neurotrophic factors like brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophic factor-3 (NT-3), and ciliary neurotrophic factor (CNTF) have been used to promote neuronal survival and stimulate axonal growth. CSPGs expressed near a lesion also inhibit migration and differentiation of endogenous oligodendrocyte progenitor cells (OPCs) in the spinal cord, and cABC treatment can neutralize this inhibition. This study examined the neurotrophins commonly used to stimulate axonal regeneration after injury and their potential effects on OPCs cultured in the presence of CSPGs. The results reveal differential effects on OPCs, with BDNF and GDNF promoting process outgrowth and NT-3 stimulating differentiation of OPCs, while CNTF appears to have no observable effect. This finding suggests that certain neurotrophic agents commonly utilized to stimulate axonal regeneration after a spinal injury may also have a beneficial effect on the endogenous oligodendroglial cells as well.

Mycobacterium vaccae nebulization protects Balb/c mice against bronchial asthma through neural mechanisms.

OBJECTIVES: Bronchial asthma can be effectively controlled but not be cured, its etiology and pathogenesis are still unclear, and there are no effective preventive measures. The key characteristic of asthma is chronic airway inflammation, and recent research has found that airway neurogenic inflammation plays an important role in asthma. We previously found that Mycobacterium vaccae nebulization protects against asthma. Therefore, this objective of this study is to explore the effect of M. vaccae nebulization on asthmatic neural mechanisms. METHODS: A total 18 of female Balb/c mice were randomized into normal, asthma control, and M. vaccae nebulization (Neb.group) groups, and mice in the Neb.group were nebulized with M. vaccae one month before the asthmatic model was established. Then, 1 month later, the mice were sensitized and challenged with ovalbumin. Twenty-four hours after the last challenge, mouse airway responsiveness; pulmonary brain-derived neurotropic factor (BDNF), neurofilament-medium length (NF-M, using NF09 antibody), and acetylcholine expression; and nerve growth factor (NGF) mRNA level were determined. RESULTS: We found that the BDNF, NF09, acetylcholine expression, and NGF mRNA level were decreased in the Neb.group compared with levels in the asthma control group. CONCLUSION: M. vaccae nebulization may protected in Balb/c mice against bronchial asthma through neural mechanisms.

Whole body vibration training promotes proprioceptive pathway for the treatment of stress urinary incontinence in rats.

Background: Stress urinary incontinence (SUI) is the most ubiquitous form of urinary incontinence in women. The therapeutic management of patients with SUI is challenging. The aim of this study is to evaluate the efficacy of whole body vibration training (WBVT) for SUI. Methods: Thirty-five female rats were randomly divided into a sham group (Sham group, n=5), SUI + WBVT group (n=15) and SUI + whole body rest group (SUI + WBR group, n=15). The SUI + WBVT group was trained as follows: frequency 30 Hz, amplitude four mm, one min/repeat, four min rest, repeated 10 times, five days/week. After the intervention, five rats were taken on the 7th, 14th and 21st day to observe the urodynamic changes, levator ani muscle and dorsal root ganglia (DRG) morphology, and to observe the expression of neurotrophic factor-3/tyrosine protein kinase C (NT-3/TrkC) by Western blot. Results: The urodynamic results showed that the difference in bladder leak point pressure/abdominal leak point pressure (BLPP/ALPP) between the Sham group and the SUI + WBR group was statistically significant (P<0.001) on 7th day, indicating successful modeling. The BLPP/ALPP of the SUI + WBVT group and the SUI + WBR group improved on 7th, 14th, and 21st day, and the BLPP/ALPP of SUI + WBVT group was higher than the SUI + WBR group. Compared with the Sham group, pathological changes appeared in the muscle shuttles in the SUI + WBVT group and SUI + WBR group. Western blot showed a gradual up-regulation of NT-3/TrkC. Conclusions: WBVT can be used to treat SUI by affecting the expression of NT-3/TrkC, improving the structural morphology of the proprioceptors, and restoring the urinary control function. This study provides evidence for the clinical practice of WBVT. Future studies could further refine the behavioral and electrophysiological aspects of the assessment.

Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer's disease.

Brain degenerations in sporadic Alzheimer's disease (AD) are observed earliest in the locus coeruleus (LC), a population of noradrenergic neurons, in which hyperphosphorylated tau protein expression and ß-amyloid (Aß) accumulation begin. Along with this, similar changes occur in the basal forebrain cholinergic neurons, such as the nucleus basalis of Meynert. Neuronal degeneration of the two neuronal nuclei leads to a decrease in neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex, which results in the accumulation of Aß and hyperphosphorylated tau protein and ultimately causes neuronal cell death in those cortices. On the other hand, a large number of epidemiological studies have shown that tooth loss or masticatory dysfunction is a risk factor for dementia including AD, and numerous studies using experimental animals have also shown that masticatory dysfunction causes brain degeneration in the basal forebrain, hippocampus, and cerebral cortex similar to those observed in human AD, and that learning and memory functions are impaired accordingly. However, it remains unclear how masticatory dysfunction can induce such brain degeneration similar to AD, and the neural mechanism linking the trigeminal nervous system responsible for mastication and the cognitive and memory brain system remains unknown. In this review paper, we provide clues to the search for such "missing link" by discussing the embryological, anatomical, and physiological relationship between LC and its laterally adjoining mesencephalic trigeminal nucleus which plays a central role in the masticatory functions.

Promising application of a novel biomaterial, light chain of silk fibroin combined with NT3, in repairment of rat sciatic nerve defect injury.

Autologous nerve transplantation is the gold standard for treating peripheral nerve defects, but it is associated with defects such as insufficient donor and secondary injury. Artificial nerve guidance conduits (NGCs) are now considered promising alternatives for bridging long nerve gaps, although exploring new biomaterials to construct NGCs remains challenging. Silk fibroin (SF) has good biocompatibility and can self-assemble in aqueous solutions. However, the lack of proximal neurotrophic factors after nerve injury is a major concern, leading to incomplete nerve regeneration. In this study, NT-3, a neurotrophin that promotes neuronal survival and differentiation, was bound to the light chain of silk fibroin (FIBL) in two ways: one was directly bound to FIBL (FIBL-NT3) and the other was a polypeptides-linker (FIBL-Linker-NT3). The design aimed to take advantage of silk fiber's character of self-assembly of heavy-light chains and test whether a flexible linker with NT3 molecule is easy to be a NT3 dimer, the active form. In vitro studies indicated that FIBL-Linker-NT3 combined with SF membranes promoted axon growth in adult rat dorsal root ganglion (DRG) neurons. Then we tested if FIBL-Linker-NT3 could self-assemble with the SF heavy chain (SFH). DTT (Dithiothreitol) was used to break the disulfide bonds between the SF light and heavy chains, and the light-chain protein was removed via dialysis. SFH was assembled using FIBL-Linker-NT3, as evidenced by the western blotting results that showed a high molecular band corresponding to SFH-FIBL-Linker-NT3. Chitosan scaffolds have been identified to provide a suitable microenvironment, so a chitosan/SF-FIBL-Linker-NT3 conduit was also constructed. Nerve transplantation of this conduit was evaluated in vivo in a rat sciatic nerve defect model. Immunohistochemical assays showed that the chitosan/SF-FIBL-Linker-NT3 group was superior to the chitosan/PBS, SF, PBS + FIBL-Linker-NT3 groups in nerve regeneration. In addition, the chitosan/SF-FIBL-Linker-NT3 conduit-transplanted group exhibited better recovery in terms of neurite length, sciatic functional index value, sensitivity to heat, time on the rotarod, wet weight ratio, cross-sectional area, compound muscle action potential, number of myelin layers, and myelin thickness in the nerve. Taking together, our study identified that FIBL-Linker-NT3 could promote axonal growth and regeneration in vivo and in vitro and is a promising candidate biomaterial for artificial NGCs.

Neurotrophic factor NT-3 displays a non-canonical cell guidance signaling function for cephalic neural crest cells.

Chemotactic cell migration is triggered by extracellular concentration gradients of molecules segregated by target fields. Neural crest cells (NCCs), paradigmatic as an accurately moving cell population, undergo wide dispersion along multiple pathways, invading with precision defined sites of the embryo to differentiate into many derivatives. This report addresses the involvement of NT-3 in early colonization by cephalic NCCs invading the optic vesicle region. The results of in vitro and in vivo approaches showed that NCCs migrate directionally up an NT-3 concentration gradient. We also demonstrated the expression of NT-3 in the ocular region as well as their functional TrkB, TrkC and p75 receptors on cephalic NCCs. On whole-mount embryo, a perturbed distribution of NCCs colonizing the optic vesicle target field was shown after morpholino cancelation of cephalic NT-3 or TrkC receptor on NCCs, as well as in situ blocking of TrkC receptor of mesencephalic NCCs by specific antibody released from inserted microbeads. The present results strongly suggest that, among other complementary cell guidance factor(s), the chemotactic response of NCCs toward the ocular region NT-3 gradient is essential for spatiotemporal cell orientation, amplifying the functional scope of this neurotrophic factor as a molecular guide for the embryo cells, besides its well-known canonical functions.

The relationship between the presence of ADHD and certain candidate gene polymorphisms in a Turkish sample.

Due to the high heritability of attention-deficit hyperactivity disorder (ADHD), parents of children with ADHD appear to represent a good sample group for investigating the genetics of the disorder. The aim of this study was to investigate the association between ADHD and six polymorphisms in five candidate genes [5-HT2A (rs6311), NET1 (rs2242447), COMT (rs4818), NTF3 (rs6332), SNAP-25 (rs3746544) and (rs1051312)]. We included 228 parents of children diagnosed with ADHD and 109 healthy parents as the control group. The polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays and analyzed using the chi-square test and the multinomial logit model. SNAP-25 (rs3746544) polymorphism was associated with loading for ADHD, while 5-HT2A (rs6311) and NET1 (rs2242447) polymorphisms were associated with ADHD. On the other hand, there was no significant association between the SNAP-25 (rs1051312), NTF3 (rs6332), or COMT (rs4818) gene polymorphisms and ADHD. In addition, we found that even if variation in the SNAP-25 gene alone does not affect the phenotype, it may nevertheless lead to the emergence of a clinical ADHD picture in the presence of other genetic factors. Our findings suggest that a combination of NET1 (rs2242447) and SNAP-25 (rs3746544) is a risk factor for ADHD. Problems associated with the noradrenergic and serotonergic systems and SNAP-25 may play a role, both alone and in interaction with one another, in the pathophysiological mechanisms of ADHD.