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Anti-neuronal autoantibodies can be transplacentally transferred during pregnancy and may cause detrimental effects on fetal development. It is unclear whether autoantibodies against synapsin-I, one of the most abundant synaptic proteins, are associated with developmental abnormalities in humans. We recruited a cohort of 263 pregnant women and detected serum synapsin-I IgG autoantibodies in 13.3% using cell-based assays. Seropositivity was strongly associated with abnormalities of fetal development including structural defects, intrauterine growth retardation, amniotic fluid disorders and neuropsychiatric developmental diseases in previous children (odds ratios of 3–6.5). Autoantibodies reached the fetal circulation and were mainly of IgG1/IgG3 subclasses. They bound to conformational and linear synapsin-I epitopes, five distinct epitopes were identified using peptide microarrays. The findings indicate that synapsin-I autoantibodies may be clinically useful biomarkers or even directly participate in the disease process of neurodevelopmental disorders, thus being potentially amenable to antibody-targeting interventional strategies in the future.

Purpose: To investigate the efficacy and underlying mechanism of action of Rhodiola rosea L. on diabetic gastroparesis (DGP) based on Synapsin-I. Methods: The extract of Rhodiola rosea L. was obtained by preparing the crude medicine of traditional Chinese medicine. The Sprague-Dawley (SD) rats were randomly allocated to three groups: normal, DGP, and DGP+Rhodiola rosea L. groups. Rats in DGP+Rhodiola rosea L. group were treated with Rhodiola rosea L. once daily for 5 weeks at a dose of 150 mg·kg-1·day-1, while rats in DGP group received an equivalent volume of saline by oral gavage. Parameters were evaluated include body weight, fasting glucose level, gastric emptying rate and gastric acid secretion. Histopathological examination of the stomach was performed by hematoxylin-eosin (H&E) staining. Immunohistochemistry, cellular immunofluorescence, as well as western blot were employed to determine the expressions of Synapsin-I and protein gene product 9.5 (PGP9.5). Results: Compared normal group, the body weight or rats in DGP group decreased, blood glucose was elevated, gastric acid secretion level decreased, and gastric emptying rate increased (p < 0.05). Besides, they also showed signs of misalignment of gastric mucosal glands, enlarged intercellular space, and significantly reduced protein expressions of PGP9.5 and Synapsin-I. Administration of Rhodiola rosea L. extract reversed the above changes in DGP rats, and also elevated the protein expression of both PGP9.5 and synapsin-I. Conclusion: Rhodiola rosea L. extract exerts a protective effect in DGP by enhancing synaptic plasticity via upregulation of expression of synapsin-I. Thus, an experimental basis has been established for the potential clinical application of Rhodiola rosea L. extract in the management of diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Maternal mortality could be a neonatal stressor that activated the HPA axis to secret glucocorticoids as a marker of stress. Brain development took place rapidly in the first 1,000 days of life. Synapsin-I was involved in the early development of the brain's nervous system. The purpose of this study was to analyze the impact of separation of Rat's pup and mothers as a maternal death model on the expression of synapsin-I in the cerebrum and cerebellum of 3 days old Rattus norvegicus pups. The control group (K1) consisted of newborn Rattus norvegicus which remained with the mother, while the treatment group (K2) consisted of newborn Rattus norvegicus which was separated from the mother. After 3 days of observation, Rattus norvegicus pups from each parent were taken with the heaviest, medium, and lowest weights to be sacrificed and examined by imonohistochemical of synapsin-I expression. Analysis of the Mann Whitney test for synapsin-I expression in Rattus norvegicus cerebrum showed a significant difference between the control group and the treatment group with a value of p=0,000 (p<0.05). Independent T test analysis of synapsin-I expression in Rattus norvegicus cerebellum also showed a significant difference between the control group and the treatment group with a value of p=0,000 (p<0.05). Synapsin-I expressions in the cerebrum and cerebellum of Rattus norvegicus pups that separated from the mothers were lower than those that not separated from the mothers. [ABSTRACT FROM AUTHOR]

Abstract The aging process is associated with structural and functional changes in the nervous system. Considering that exercise can improve the quality of life of the elderly, the aim of this study was to evaluate the effects of exercise protocols with different motor demands on synaptic protein expression (i.e., synapsin-I and synaptophysin). Cognitive and motor brain areas and the motor performance of adult and aged animals were analyzed. Adult (7 months old) and aged (18 months old) male Wistar rats were used. Animals were divided into the following groups: treadmill exercise (TE, rhythmic motor activity), acrobatic exercise (AE, complex motor activity) and sedentary (SED, control). The animals were exposed to exercise 3 times per week for 8 weeks. The brains were collected for immunohistochemistry and immunoblotting assays. Our results showed that both types of exercise induced changes in motor performance and synaptic protein expression in adult and aged animals. However, acrobatic exercise promoted a greater number of changes, mainly in the aged animals. In addition, protein expression changes occurred in a greater number of brain areas in the aged animals than in adult animals. There were clear increases in synapsin-I expression in all areas analyzed of aged animals only after acrobatic exercises. On the other hand, synaptophysin increased in the same areas but with both types of exercise. Thus, in general, our data suggest that even at advanced ages, when the aging process is already in progress, initiating physical training may be beneficial to generate neuroplasticity that can improve motor performance. Highlights • Aging, motor performance, synaptic proteins and neuroplasticity. • Pre-synaptic protein changes under different exercise protocols. • Motor performance improvement after exercise training. • Synaptic protein expression differences between adults and aged exercised rats. [ABSTRACT FROM AUTHOR]

Anti-neuronal autoantibodies can be transplacentally transferred during pregnancy and may cause detrimental effects on fetal development. It is unclear whether autoantibodies against synapsin-I, one of the most abundant synaptic proteins, are associated with developmental abnormalities in humans. We recruited a cohort of 263 pregnant women and detected serum synapsin-I IgG autoantibodies in 13.3% using cell-based assays. Seropositivity was strongly associated with abnormalities of fetal development including structural defects, intrauterine growth retardation, amniotic fluid disorders and neuropsychiatric developmental diseases in previous children (odds ratios of 3-6.5). Autoantibodies reached the fetal circulation and were mainly of IgG1/IgG3 subclasses. They bound to conformational and linear synapsin-I epitopes, five distinct epitopes were identified using peptide microarrays. The findings indicate that synapsin-I autoantibodies may be clinically useful biomarkers or even directly participate in the disease process of neurodevelopmental disorders, thus being potentially amenable to antibody-targeting interventional strategies in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Maternal dexamethasone (DEX; a glucocorticoid receptor agonist) exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg) or vehicle (VEH, water) daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

Abnormal Glu release occurs in the spinal cord of SOD1 G93A mice, a transgenic animal model for human ALS. Here we studied the mechanisms underlying Glu release in spinal cord nerve terminals of SOD1 G93A mice at a pre-symptomatic disease stage (30 days) and found that the basal release of Glu was more elevated in SOD1 G93A with respect to SOD1 mice, and that the surplus of release relies on synaptic vesicle exocytosis. Exposure to high KCl or ionomycin provoked Ca 2+ -dependent Glu release that was likewise augmented in SOD1 G93A mice. Equally, the Ca 2+ -independent hypertonic sucrose-induced Glu release was abnormally elevated in SOD1 G93A mice. Also in this case, the surplus of Glu release was exocytotic in nature. We could determine elevated cytosolic Ca 2+ levels, increased phosphorylation of Synapsin-I, which was causally related to the abnormal Glu release measured in spinal cord synaptosomes of pre-symptomatic SOD1 G93A mice, and increased phosphorylation of glycogen synthase kinase-3 at the inhibitory sites, an event that favours SNARE protein assembly. Western blot experiments revealed an increased number of SNARE protein complexes at the nerve terminal membrane, with no changes of the three SNARE proteins and increased expression of synaptotagmin-1 and β-Actin, but not of an array of other release-related presynaptic proteins. These results indicate that the abnormal exocytotic Glu release in spinal cord of pre-symptomatic SOD1 G93A mice is mainly based on the increased size of the readily releasable pool of vesicles and release facilitation, supported by plastic changes of specific presynaptic mechanisms. [ABSTRACT FROM AUTHOR]

Data on olfactory bulb (OB) development in human fetuses in the stages from the 8th week to birth is provided. Immunohistochemical markers of presynaptic terminals (anti-SNAP-25, synapsin-I, and synaptophysin) were used to evaluate the maturation of the OB. Differentiation of the OB layers begins from the periphery, which indirectly confirms that growth of the olfactory nerve fibers induces not only the anatomical differentiation of the OB but also the differentiation of its functional layers. The sites of the developing glomeruli are revealed using the immunohistochemical procedure prior to the stage in which distinct glomeruli can be identified using a common histological procedure. The OB conductive system demonstrates immunoreactivity with the antibodies to presynaptic proteins at all stages starting with the 10th-11th weeks of fetal development. Four stages of OB development are described. All functional layers of the OB are mature at the 22nd week stage. Further differentiation of the neuroblasts in the OB, including lamina formation of the internal granular layer and the glomerular layer development, and the growth of the OB continue after the 20th-22nd week stage until 38th-40th weeks of fetal development. Patterns of the immunoreactivity with antibodies to SNAP-25, synapsin-I, and synaptophysin at the 38th-40th weeks of prenatal development are fully consistent with those of the adult OB. Complete maturity of the human OB is reached at the 38th-40th week of prenatal development. [ABSTRACT FROM AUTHOR]

In order to characterize synaptic involvement in human spongiform encephalopathies, the expression of synaptic vesicle-associated proteins, synaptophysin and synapsin-I, and presynaptic plasma membrane proteins, synaptosomal-associated protein of 25 kDa (SNAP-25) and syntaxin-I, was examined in the brains of four patients who had suffered from sporadic Creutzfeldt–Jakob disease. Nerve cell loss, spongiform degeneration, astrocytosis, and deposition of prion protein (PrP) were observed in the cerebral cortex in every case. Decreased immunoreactivity for synaptophysin, synapsin-I, SNAP-25, and syntaxin-I was observed in the cerebral cortex in every case, thus showing generalized reduction of proteins involved in exocytosis of synaptic vesicles in the brains of patients with spongiform encephalopathy. Upregulation of synaptophysin and SNAP-25, a feature associated with βA4 deposits in Alzheimer's disease (AD), was not observed in association with PrP deposition. The present results indicate that synaptic pathology is a major event in spongiform encephalopathy, and suggest that synaptic loss, together with neuron loss and selective involvement of certain populations of local-circuit neurons, as shown in other studies, may account for the dramatic neurological decay and for the main neurological symptoms in patients with CJD.

Abstract: It is well known that autophagy, a cellular stress response to degrade damaged components, can be activated by many nanoparticles. We have demonstrated that CdSe/ZnS quantum dots (QDs), which are widely applied in vitro for diagnostics and cellular imaging, can impair synaptic transmission and synaptic plasticity in the dentate gyrus (DG) area, but the mechanism is still unclear. Here we show that elevated autophagy is at least partly responsible for this synaptic dysfunction induced by QDs in vivo. QDs elicited autophagy in the HeLa cells and cultured hippocampal neurons as well, accompanied with GFP-light chain protein 3 (LC3) puncta dots and autophagosome formation, extensive conversion of LC3-I to LC3-II and a significant decrease of p62. Furthermore, we found that autophagy inhibitors (wortmannin, 3-MA or chloroquine) suppressed QDs-induced autophagic flux, partly blocked LTP impairment, coincident with down-regulation of synapsin-I and synapse deficits by QDs in the hippocampal CA1 area. Our studies have important implications in providing a potential clinical remedy for brain damage caused by nanomaterials and in designing safer nanoparticles. [Copyright &y& Elsevier]

Abstract: Stroke is a leading cause of morbidity and mortality worldwide. Recovery of motor function after stroke can be modified by post-injury experience, but most of surviving patients exhibit persistence of the motor dysfunctions even after rehabilitative therapy. In this study we investigated if skilled and unskilled training induce different motor recovery and brain plasticity after experimental focal ischemia. We tested this hypothesis by evaluating the motor skill relearning and the immunocontent of Synapsin-I, PSD-95 and GFAP (pre and post-synaptic elements, as well as surrounding astroglia) in sensorimotor cortex of both hemispheres 6 weeks after endothelin-1-induced focal brain ischemia in rats. Synapsin-I and PSD-95 levels were increased by skilled training in ischemic sensorimotor cortex. The content of GFAP was augmented as a result of focal brain ischemia in ischemic sensorimotor cortex and that was not modified by rehabilitation training. Unexpectedly, animals remained permanently impaired at the end of motor/functional evaluations. Significant modifications in protein expression were not observed in undamaged sensorimotor cortex. We conclude that skilled motor activity can positively affect brain plasticity after focal ischemia despite of no functional improvement in conditions here tested. [Copyright &y& Elsevier]

Abstract: Axonal projections originating from the mammillary bodies represent important pathways that are essential for spatial information processing. Mammillothalamic tract is one of the main efferent projection systems of the mammillary body belonging to the limbic “Papez circuit”. This study was aimed to describe the schedule of the mammillothalamic tract development in the rat using carbocyanine dye tracing. It was shown for the first time that fibers of the mammillothalamic tract being the collaterals of the mammillotegmental tract axons start bifurcating from the mammillotegmental tract on E17. The axons of the mammillothalamic tract grow simultaneously and reach the ventral region of the anterior thalamus where they form first terminal arborizations on E20–E21. Ipsilateral projections from the medial mammillary nucleus to the anteromedial and anteroventral thalamic nuclei develop from E20 to P6. Bilateral projections from the lateral mammillary nucleus to the anterodorsal thalamic nuclei develop later, on P3–P6, after the formation of the thalamic decussation of the mammillary body axons. Unique spatial and temporal pattern of the perinatal development of ascending mammillary body projections to the anterior thalamic nuclei may reflect the importance of these connections within the limbic circuitry. [Copyright &y& Elsevier]

Abstract: Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins used to color food (E163), has been reported to possess a variety of biological activities, including anti-oxidant, anti-tumor, and anti-inflammatory. The effect of PSPC on the spatial learning and memory of mice treated with d-galactose (d-gal) was evaluated by the Morris water maze; d-gal-treated mice had decreased performance compared with mice in the vehicle and PSPC groups, while the PSPC+ d-gal group showed significantly shortened escape latency to platform, increased swimming speed, more target quadrant search time and more platform crossings as compared with the d-gal group. Brain functions, such as memory formation and recovery of function after injury, depend on proper regulation of the expression levels of the pre- and post-synaptic proteins. We investigated the expression of four pre-synaptic proteins (growth-associated protein-43, synapsin-I, synaptophysin, and synaptotagmin) and two post-synaptic proteins (post-synaptic density protein-95 and Ca2+/calmodulin-dependent protein kinase II) in the hippocampus and cerebral cortex, respectively, in response to different treatments. Western blotting analysis showed that there were significant decreases in the expression of these representative synaptic proteins in the hippocampus and cerebral cortex of d-gal-treated mice. Interestingly, these decreased expression levels of synaptic proteins could be reversed by PSPC. The levels of expression of these representative synaptic proteins in mice treated with PSPC alone were not significantly different from those in untreated mice. The results of this study suggested that memory impairment and synaptic protein loss in d-gal-treated mice may be improved by treatment with PSPC. [Copyright &y& Elsevier]

Slow component-b (SCb) translocates ∼200 diverse proteins from the cell body to the axon and axon tip at average rates of ∼2- 8 mm/d. Several studies suggest that SCb proteins are cotransported as one or more macromolecular complexes, but the basis for this cotransport is unknown. The identification of actin and myosin in SCb led to the proposal that actin filaments function as a scaffold for the binding of other SCb proteins and that transport of these complexes is powered by myosin: the "microfilament-complex" model. Later, several SCb proteins were also found to bind F-actin, supporting the idea, but despite this, the model has never been directly tested. Here, we test this model by disrupting the cytoskeleton in a live-cell model system wherein we directly visualize transport of SCb cargoes. We focused on three SCb proteins that we previously showed were cotransported in our system: α-synuclein, synapsin-I, and glyceraldehyde-3- phosphate dehydrogenase. Disruption of actin filaments with latrunculin had no effect on the velocity or frequency of transport of these three proteins. Furthermore, cotransport of these three SCb proteins continued in actin-depleted axons.Weconclude that actin filaments do not function as a scaffold to organize and transport these and possibly other SCb proteins. In contrast, depletion of microtubules led to a dramatic inhibition of vectorial transport of SCb cargoes. These findings do not support the microfilament-complex model, but instead indicate that the transport of protein complexes in SCb is powered by microtubule motors. [ABSTRACT FROM AUTHOR]

Abstract: The present work reports that activation of P2X7 receptor induces synaptic vesicle release in granule neurons and phosphorylation of synapsin-I by calcium–calmodulin-dependent protein kinase II (CaMKII), which in turn modulates secretory event. ATP, in absence of magnesium, induced a concentration-dependent glutamate release with an EC50 value of 1.95μM. The involvement of P2X7 receptor was suggested when maximal secretory response was significantly reduced by the selective P2X7 antagonist Brilliant Blue G (BBG; 100nM) and abolished by removing extracellular Ca2+. The involvement of P2X7 receptor on synaptic vesicle release was confirmed by measuring the release of FM 1-43 dye. In this case, pharmacological activation of P2X7 was achieved with the more selective agonist 2′-3′-o-(4-benzoylbenzoyl)-adenosine 5′-triphosphate (BzATP; 100μM) showing a significant FM 1-43 release that was blocked by BBG (100nM), by Zn2+ ions (100μM), both P2X7 blockers, but not by suramin (100μM), antagonist of P2X1, P2X2, P2X3 and P2X5. In addition, BzATP, through P2X7 receptor activation, significantly increased the phosphorylation of synapsin-I, the main presynaptic target of CaMKII. Both effects mediated by BzATP were inhibited by the CaMKII inhibitors KN-62 (10μM) and KN-93 (10μM). These results suggest, therefore, that Ca2+ entrance mediated by P2X7 receptor induces glutamate release and in parallel synapsin-I phosphorylation. [Copyright &y& Elsevier]

Abstract: Mood disorders are the most common psychiatric disorders. Although the mechanisms implicated in the genesis of mood disorders are still unclear, stress is known to predispose to depression, and recently, studies have related hippocampal neurogenesis and apoptosis to depression. In the present study we first examined the balance between cell birth–death in the hippocampus and subventricular zone (SVZ) of pre-pubertal and adult rats subjected to chronic-mild-stress (CMS). CMS led to increased corticosterone secretion and induced depressive-like symptoms (assessed in the forced-swimming test); these endocrine and behavioral effects were paralleled by decreased hippocampal, but not SVZ, cell proliferation/differentiation and by increased apoptotic rate. In order to determine if lithium, a known mood stabilizer with antidepressant properties, could prevent the stress-induced events, we analyzed the same parameters in a group of rats treated with lithium during the stress exposure period (CMS+Li) and observed that the hormonal, behavioral and cell turnover effects of CMS were abrogated in these animals. Subsequently, to search for possible pathways through which CMS and lithium influence behavior, cell fate and synaptic plasticity, we analyzed the expression of glycogen-synthase-kinase-3β (GSK-3β), as well as some of its downstream targets (B-cell-CLL/lymphoma2-associated athanonege (BAG-1) and synapsin-I). CMS increased GSK-3β and decreased synapsin-I and BAG-1 expression in the hippocampus. Interestingly, co-administration of lithium precluded the CMS-induced effects in GSK-3β, synapsin-I and BAG-1 expression. Our observation that specific inhibition of this kinase with AR-A014418 blocked the effects of CMS in depressive-like behavior and in BAG-1 and synapsin-I expression confirmed the involvement of the GSK-3β pathway in stress-induced effects. In summary, these results reveal that lithium, by regulating the activity of GSK-3β, prevents the deleterious effects of stress on behavior and cellular functions. [Copyright &y& Elsevier]

Abstract: Exercise increases brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response-element binding protein (pCREB), insulin-like growth factor (IGF-I) and synapsin-I, each of which has been implicated in neuroplastic processes underlying recovery from ischemia. In this study we examined the temporal profile (0, 30, 60 and 120 min following exercise) of these proteins in the hippocampus and sensorimotor cortex following both motorized (60 min) and voluntary (12 h) running, 2 weeks after focal ischemia. Our goal was to identify the optimal training paradigms (intensity, duration and frequency) needed to integrate endurance exercise in stroke rehabilitation. Therefore we utilized telemetry to measure changes in heart rate with both exercise methods. Our findings show that although the more intense, motorized running exercise induced a rapid increase in BDNF, the elevation was more short-lived than with voluntary running. Motorized running was also associated with higher levels of synapsin-I in several brain regions but simultaneously, a more pronounced increase in the stress hormone, corticosterone. Furthermore, both forms of exercise resulted in decreased phosphorylation of CREB and downregulation of synapsin-I in hippocampus beginning 30 to 60 min after the exercise bout. This phenomenon was more robust after motorized running, the method that generated higher heart rate and serum corticosterone levels. This immediate stress response is likely specific to acute exercise and may diminish with repeated exercise exposure. The present data illustrate a complex interaction between different forms of exercise and proteins implicated in neuroplasticity. For clinical application, frequent lower intensity exercise episodes (as in voluntary running wheels), which may be safer to provide to patients with stroke, has a delayed but sustained effect on BDNF that may support brain remodeling after stroke. [Copyright &y& Elsevier]

Abstract: Several evidences have demonstrated that adult mammals could achieve a wide range of spontaneous sensory-motor recovery after spinal cord injury by means of various forms of neuroplasticity. In this study we evaluated the possibility that after low-thoracic spinal cord hemisection in the adult rat, significant hindlimb locomotor recovery could occur, and that this recovery may be driven, at least in part, by mechanisms of synaptic plasticity. In order to address these issues, we measured the expression levels of synapsin-I and brain-derived neurotrophic factor by Western blotting, at various time points after hemisection and correlated them with the motor performance on a grid walk test. Regression analysis showed that the expression of synapsin-I was strongly correlated with the spontaneous recovery of hindlimb locomotion (R =0.78). Conversely, neither the expression levels of synapsin-I nor the locomotor recovery were associated with the expression of brain-derived neurotrophic factor. Overall results indicate that after spinal cord hemisection, substantial recovery of hindlimb locomotion could occur spontaneously, and that synaptic plasticity within spinal circuitries below the level of the lesion, could be an important mechanism involved in these processes. [Copyright &y& Elsevier]

The comparative localization of two prominent synaptic proteins, synapsin-I (Syn-I) and PSD-95, was investigated in slices of developing (P3–P21) rat cerebellar cortex using double- or triple-label fluorescence immunohistochemistry and confocal microscopy. During the first postnatal week, Syn-I and PSD-95 immunoreactive (IR) puncta were strongly concentrated in the Purkinje cell layer (PCL) where they circumscribed irregularly shaped PC somata, forming pericellular nests that likely correspond to early climbing fiber synapses. PSD95 and Syn-I puncta also were found along the shafts and at the tips of growing PC dendrite branches labeled with calbindin. During the second postnatal week, synaptic puncta were lost from the PC layer, while many new puncta were added to the molecular layer (ML). At P10, about half of the PCs were circumscribed by PSD-95 or Syn-I puncta, whereas at P14 no PCs were circumscribed. By P14, PSD95 and Syn-I became most strongly localized to many small puncta in the ML and to large clusters at mossy fiber rosettes in the glomerular layer (GL) where PSD-95 often encircled Syn-I clusters. Some large clusters in the GL contained only PSD-95 or Syn-I, but not both, suggesting differential growth or remodeling of pre- and post-synaptic structures. No PSD-95 staining of pre-synaptic terminal pinceau was observed during the first 3 weeks of postnatal development. Thus, in relation to PCs, there is a developmental shift in PSD-95 localization whereby, first, it is concentrated on PC cell bodies and short dendrites (P3–P7), then it is lost on PC cell bodies (P7–14) and becomes localized almost exclusively to PC dendrites (P14–P21). [Copyright &y& Elsevier]

Dystrophic axons in a 2-year-old male Rottweiler with neuroaxonal dystrophy have shown synaptophysin, synapsin-I, synaptosomal-associated protein of 25 kDa (SNAP-25), Rab 3a, and α-synuclein immunoreactivity. Similar findings have been observed in isolated dystrophic axons in the nuclei gracillis and cunneatus in five dogs aged between 14 and 18 years. Abnormal expression of integral synaptic vesicle, synaptic vesicle-associated presynaptic plasma membrane and cytosolic proteins, which participate in the trafficking, docking and fusion of the synaptic vesicle to the plasma membrane, suggest severe disruption of axonal transport in dystrophic axons in canine neuroaxonal dystrophy. [ABSTRACT FROM AUTHOR]

Exosomes derived from the cerebral endothelial cells play essential roles in protecting neurons from hypoxia injury, but little is known regarding the biological effects and mechanisms of exosomes on brain plasticity. In this study, exosomes were isolated from rodent cerebral endothelial cells (bEnd.3 cells) by ultracentrifugation, either endothelial cell-derived exosomes (EC-Exo) or PBS was injected intraventricularly 2 h after the middle cerebral artery occlusion/reperfusion (MCAO/R) model surgery in the Exo group and control group, respectively. Sham group rats received the same surgical but not ischemic procedure. We evaluated the motor function of rats after MCAO/R, and the foot-fault rate of the Exo group was significantly lower than that of the control group within 23 days ( p < 0.05); the Catwalk analysis also showed gait difference between two groups ( p < 0.05). On day 28 after MCAO/R, we euthanized the rats, removed the motor cortex from the brain, and then sequenced the genes by using GO and KEGG to find transcriptome analysis of biological terms and functional annotations: The pathway enrichment revealed that the function of synaptic transmission, regulation of synaptic plasticity, and regulation of synaptic vesicle cycle was significantly enriched with the Exo group than control group. Furthermore, the upregulation of synapsin-I expression in the motor cortex ( p < 0.05) as well as the increase of the length of the dendrites were found in the Exo group ( p < 0.05) than the control group. We determined the content of exosome microRNA levels, and microRNA-126-3p was the highest (TPM) by transcriptome analysis. Moreover, the microRNA-126-3p protected PC12 cells from apoptosis and increased neurite outgrowth, illustrating the mechanism of how exosomes play a role in altering brain plasticity. This study demonstrated that EC-Exo promoted functional motor recovery in the MCAO/R model, exosomes were critical for the reconstruction of synaptic function in ischemic brain injury, and microRNA-126-3p from EC-Exo could serve as a treatment for nerve damage.

Transplantation of bone marrow stromal cells (BMSCs) is regarded as a promising candidate for the spinal cord injury (SCI). In the present study, we investigated whether treadmill exercise potentiate the effect of BM-SCs transplantation on the functional recovery in the SCI rats. The spinal cord contusion injury applied at the T9-T10 level using the impactor. Cultured BMSCs were transplanted into the lesion at 1 week after SCI induction. Treadmill exercise was conducted for 6 weeks. Basso-Beattie-Bresnahan (BBB) scale for locomotor function was determined. Sprouting axons in the lesion cavity were detected by immunofluorescence staining for neurofilament-200. Brain-derived neurotrophic factor (BDNF) and synapsin-I expressions were analyzed using western blotting. BMSCs transplantation improved BBB score and increased expressions of neurofilament-200, BDNF, and synapsin-I in the SCI rats. Treadmill exercise potentiated the improving effect of BMSCs transplantation on BBB score in the SCI rats. This potentiating effect of treadmill exercise could be ascribed to the enhancement of BDNF expression in the SCI rats., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported.