Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene family of neuron-specific phosphoproteins in maintaining brain physiology. In the recent times, increasing evidence has established the relevance of alterations in synapsins as a major determinant in many neurological disorders. Here, we give a comprehensive description of the diverse roles of the synapsin family and the underlying molecular mechanisms that contribute to several neurological disorders. These physiologically important roles of synapsins associated with neurological disorders are just beginning to be understood. A detailed understanding of the diversified expression of synapsins may serve to strategize novel therapeutic approaches for these debilitating neurological disorders.
Animals ; Central Nervous System Diseases ; physiopathology ; Humans ; Synapsins ; physiology

OBJECTIVES: Synapsin III near VCFS region on chromosome 22q affects. It could be an interesting candidate gene for schizophrenia. D22S280 is a highly polymorphic genetic marker residing in synapsin III. We examined association of D22S280 marker on synapsin III with Korean patients with schizophrenia. METHODS: The subjects were 46 male Korean patients with schizophrenia and 60 male normal controls. Using polymerase chain reaction, gel electrophoresis, ABI 310 genetic analyzer, and GeneScan Collection 3.1 software, we confirmed genotypes of D22S280 marker. We examined Hardy-Weinberg equilibrium and case-control association using SAS/Genetic 9.1.3. RESULTS: Genotypes of both schizophrenia and control groups were in Hardy-Weinberg equilibrium. We could not find any significant statistical differences in allele-wise(chi-square=10.4, df=6, p=0.098) and genotype-wise (chi-square=22.1 df=19, p=0.258) analyses of D22S280 marker between schizophrenia and normal controls. Individual allele analyses with df=1 showed significant differences in A1(p=0.025) and A7(p=0.034) allele, which were not significant following Bonferroni corrections(A1 : p=0.177, A7 : p=0.235). CONCLUSION: We couldn't find any association between schizophrenia and the synapsin III gene. Given the small number of subjects studied, further investigations are needed.
Alleles ; Case-Control Studies ; Electrophoresis ; Genetic Markers ; Genotype ; Humans ; Male* ; Polymerase Chain Reaction ; Schizophrenia* ; Synapsins*

Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus.
Animals ; Axis, Cervical Vertebra* ; Axons* ; Dentate Gyrus ; Entorhinal Cortex ; Epilepsy, Temporal Lobe* ; Hippocampus* ; Melatonin* ; Neurons* ; Rats ; Status Epilepticus ; Synapsins ; Temporal Lobe*

Time-dependent translocational changes of Synapsin I (SyI), a synaptic vesicle-associated phosphoprotein and its involvement in the axonal transport were investigated in the regenerating axonal sprouts. A weak SyI immunoreactivity (IR) was found in the axoplasm of normal axons. Rat sciatic nerves were crush-injured by ligating with 1-0 silk thread at the mid-thigh level and released from the ligation 24 h later. At various times after release, immunocytochemistry was performed. SyI was translocated from the proximal to the distal site of ligation and also involved in the sprouting of regenerating axons. The distribution patterns of SyI IR were changed in the crush-injured nerves. SyI immunoreactive thin processes were strongly appeared in the proximal region from 1 h after release. After 3 h, a very strong IR was expressed. The intense SyI immunoreactive thin processes were elongated distally and were changed the distribution pattern by time-lapse. After 12 h, strong immunoreactive processes were extended to the ligation crush site. At 1 day, a very intense IR was expressed. At 2 days, immunoreactive thin processes extended into the distal region over the ligation crush site and strong IR was observed after 3 days. SyI was accumulated in the proximal region at the early phases after release. These results suggest that SyI may be related to the translocation of vesicles to the elongated membranes by a fast axonal transport in the regenerating sprouts.
Animals ; Axonal Transport ; Axons/*physiology/ultrastructure ; Immunohistochemistry ; Male ; Nerve Crush ; Nerve Regeneration/*physiology ; Protein Transport ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve/physiology ; Synapsins/*metabolism ; Time Factors

OBJECTIVETo evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period.

METHODSTwo male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot.

RESULTSGFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05).

CONCLUSIONSEarly postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.

Animals ; Animals, Newborn ; Brain ; drug effects ; metabolism ; Corpus Striatum ; drug effects ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Synapsins ; metabolism

Motor units comprise a motoneuron and the muscle fibers it innervates. Neuromuscular transmission is tightly regulated to match the activity of individual motor units. Activity-dependent release of neuromodulators at the neuromuscular junction (NMJ) determines the efficacy of transmission. The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) are produced by motoneurons and muscle fibers, and their release by skeletal muscle is regulated by muscle activity. BDNF and NT-4 enhance both spontaneous and evoked synaptic transmission at NMJs via activation of the tyrosine kinase receptor B (TrkB). Improvements in neuromuscular transmission may result from increased release of synaptic vesicles, either by presynaptic alterations in Ca(2+) transients or facilitated vesicular exocytosis. In fact, BDNF potentiates intracellular Ca(2+) release presynaptically and BDNF-induced TrkB activation also results in phosphorylation of synapsin I via mitogen activated protein kinase, which increases the number of synaptic vesicles available for release. Neurotrophins may also regulate synaptic transmission at the NMJ by increasing local release of neuregulin or other nerve-derived modulators. We review recent studies on the regulation of neuromuscular transmission, the motor unit-specific properties of NMJs and the effects of neurotrophins on synaptic efficacy at the NMJ.
Animals ; Brain-Derived Neurotrophic Factor ; physiology ; Calcium ; metabolism ; Humans ; Nerve Growth Factors ; physiology ; Neuromuscular Junction ; physiology ; Neuronal Plasticity ; Receptor, trkB ; metabolism ; Synapses ; metabolism ; Synapsins ; metabolism ; Synaptic Vesicles

The loss of neurons and synaptic contacts following cerebral ischemia may lead to a synaptic plastic modification, which may contribute to the functional recovery after a brain lesion. Using synapsin I and GAP-43 as markers, we investigated the neuronal cell death and the synaptic plastic modification in the rat hippocampus of a middle cerebral artery occlusion (MCAO) model. Cresyl violet staining revealed that neuronal cell damage occurred after 2 h of MCAO, which progressed during reperfusion for 2 weeks. The immunoreactivity of synapsin I and GAP-43 was increased in the stratum lucidum in the CA3 subfield as well as in the inner and outer molecular layers of dentate gyrus in the hippocampus at reperfusion for 2 weeks. The immunoreactivity of phosphosynapsin was increased in the stratum lucidum in the CA3 subfield during reperfusion for 1 week. Our data suggest that the increase in the synapsin I and GAP-43 immunoreactivity probably mediates either the functional adaptation of the neurons through reactive synaptogenesis from the pre-existing presynaptic nerve terminals or the structural remodeling of their axonal connections in the areas with ischemic loss of target cells. Furthermore, phosphosynapsin may play some role in the synaptic plastic adaptations before or during reactive synaptogenesis after the MCAO.
Animals ; Axons ; Brain ; Brain Ischemia ; Cell Death ; Dentate Gyrus ; GAP-43 Protein* ; Hippocampus* ; Infarction, Middle Cerebral Artery* ; Middle Cerebral Artery* ; Neurons ; Plastics ; Rats* ; Reperfusion ; Synapsins* ; Viola

O-linked N-acetylglucosamine (O-GlcNAc) represents a key regulatory post-translational modification (PTM) that is reversible and often reciprocal with phosphorylation of serine and threonine at the same or nearby residues. Although recent technical advances in O-GlcNAc site-mapping methods combined with mass spectrometry (MS) techniques have facilitated study of the fundamental roles of O-GlcNAcylation in cellular processes, an efficient technique for examining the dynamic, reciprocal relationships between O-GlcNAcylation and phosphorylation is needed to provide greater insights into the regulatory functions of O-GlcNAcylation. Here, we describe a strategy for selectively identifying both O-GlcNAc- and phospho-modified sites. This strategy involves metal affinity separation of O-GlcNAcylated and phosphorylated peptides, beta-elimination of O-GlcNAcyl or phosphoryl functional groups from the separated peptides followed by dithiothreitol (DTT) conjugation (BEMAD), affinity purification of DTT-conjugated peptides using thiol affinity chromatography, and identification of formerly O-GlcNAcylated or phosphorylated peptides by MS. The combined metal affinity separation and BEMAD approach allows selective enrichment of O-GlcNAcylated peptides over phosphorylated counterparts. Using this approach with mouse brain synaptosomes, we identified the serine residue at 605 of the synapsin-1 peptide, 603QASQAGPGPR612, and the serine residue at 692 of the tau peptide, 688SPVVSGDTSPR698, which were found to be potential reciprocal O-GlcNAcylation and phosphorylation sites. These results demonstrate that our strategy enables mapping of the reciprocal site occupancy of O-GlcNAcylation and phosphorylation of proteins, which permits the assessment of cross-talk between these two PTMs and their regulatory roles.
Acetylglucosamine/*metabolism ; Amino Acid Sequence ; Animals ; Brain/*metabolism ; Chromatography, Affinity ; Glycosylation ; Mice ; Molecular Sequence Data ; Peptides/isolation & purification ; Phosphorylation ; Synapsins/chemistry/*metabolism ; Synaptosomes/*metabolism ; Tandem Mass Spectrometry ; tau Proteins/chemistry/*metabolism

OBJECTIVETo demonstrate the prognostic value of neuroendocrine clone on colorectal carcinoma.

METHODSThe immunochemistry methods were used to investigate the percent of neuroendocrine carcinoma in 73 human colorectal carcinoma. Retrospective analysis and follow-up were carried out in all patients.

RESULTSIn all 73 cases of colorectal carcinoma, the total percentage of neuroendocrine carcinoma was 17.8%. Neuroendocrine carcinoma included 11 synapse positive, 6 chromogranin positive and 4 both positive. The major factors related to the prevalence of neuroendocrine carcinoma were sex, age, tumor location and Dukes' stage. And the 1-year survival rate of the patients who suffered from neuroendocrine carcinoma is obviously lower than that of other colorectal carcinoma.

CONCLUSIONSThe neuroendocrine carcinoma is a special kind of human colorectal carcinoma, and neuroendocrine clone may be a new marker of the malignant potency. The neuroendocrine clone has its prognostic value and may be a novel therapeutic target.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Neuroendocrine ; metabolism ; mortality ; pathology ; Chromogranins ; biosynthesis ; Colorectal Neoplasms ; metabolism ; mortality ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Survival Rate ; Synapsins ; biosynthesis

AIMTo study the mechanism of ginsenosides Rg1 and Rb1 promoting glutamic acid release from PC12 cells.

METHODSThe amount of glutamic acid released from PC12 cells was measured by high performance liquid chromatography (HPLC). The effect of Rg1 and Rb1 on the phosphorylation of synapsins was detected with immunofluorescent staining and Western blotting.

RESULTSBoth Rg1 (10 micromol x L(-1)) and Rb1 (10 micromol x L(-1)) increased glutamic acid release from PC12 cells. The release of glutamic acid was decreased by pre-incubating with the PKA inhibitor H89. H89 inhibited the release of glutamic acid induced by Rb1, but had no effect on the release of glutamic acid induced by Rg1. Moreover, Rb1 enhanced the phosphorylation of synapsins via PKA pathway, Rg1 was out of touch with this.

CONCLUSIONRb1 may promote release of neurotransmitters by increasing the phosphorylation of synapsins via PKA pathway, whereas the up-regulation of neurotransmitters release induced by Rg1 is independent of the phosphorylation of synapsins.

Animals ; Blotting, Western ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Fluorescent Antibody Technique ; Ginsenosides ; pharmacology ; Glutamic Acid ; secretion ; Isoquinolines ; pharmacology ; Neurotransmitter Agents ; secretion ; PC12 Cells ; Phosphorylation ; Rats ; Sulfonamides ; pharmacology ; Synapsins ; metabolism