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The American Journal of Pathology Dec 1999Synaptophysin is a protein involved in neurotransmitter exocytosis and is a neuroendocrine marker. We studied synaptophysin immunohistochemical expression in 35 human...
Synaptophysin is a protein involved in neurotransmitter exocytosis and is a neuroendocrine marker. We studied synaptophysin immunohistochemical expression in 35 human liver specimens (normal and different pathological conditions), in rat models of galactosamine hepatitis and carbon tetrachloride-induced cirrhosis, and in freshly isolated rat stellate cells. Synaptophysin reactivity was present in perisinusoidal stellate cells in both human and rat normal liver biopsies. The number of synaptophysin-reactive perisinusoidal cells increased in pathological conditions. Double staining for alpha-smooth muscle actin and synaptophysin, detected by confocal laser scanning microscopy, unequivocally demonstrated colocalization of both markers in lobular stellate cells. In addition, freshly isolated rat stellate cells expressed synaptophysin mRNA (detected by polymerase chain reaction) and protein. Finally, electron microscopy showed the presence of small electron translucent vesicles, comparable to the synaptophysin-reactive synaptic vesicles in neurons, in stellate cell projections. We conclude that synaptophysin is a novel marker for quiescent as well as activated hepatic stellate cells. Together with the stellate cell's expression of neural cell adhesion molecule, glial fibrillary acidic protein, and nestin, this finding raises questions about its embryonic origin and its differentiation. In addition, the presence of synaptic vesicles in stellate cell processes suggests a hitherto unknown mechanism of interaction with neighboring cells.
Topics: Animals; Biomarkers; Humans; Immunohistochemistry; Liver; Liver Diseases; Male; RNA, Messenger; Rats; Rats, Inbred WKY; Reverse Transcriptase Polymerase Chain Reaction; Synaptophysin
PubMed: 10595912
DOI: 10.1016/S0002-9440(10)65501-0 -
ELife May 2019Synaptophysins 1 and 2 and synaptogyrins 1 and 3 constitute a major family of synaptic vesicle membrane proteins. Unlike other widely expressed synaptic vesicle proteins...
UNLABELLED
Synaptophysins 1 and 2 and synaptogyrins 1 and 3 constitute a major family of synaptic vesicle membrane proteins. Unlike other widely expressed synaptic vesicle proteins such as vSNAREs and synaptotagmins, the primary function has not been resolved. Here, we report robust elevation in the probability of release of readily releasable vesicles with both high and low release probabilities at a variety of synapse types from knockout mice missing all four family members. Neither the number of readily releasable vesicles, nor the timing of recruitment to the readily releasable pool was affected. The results suggest that family members serve as negative regulators of neurotransmission, acting directly at the level of exocytosis to dampen connection strength selectively when presynaptic action potentials fire at low frequency. The widespread expression suggests that chemical synapses may play a frequency filtering role in biological computation that is more elemental than presently envisioned.
EDITORIAL NOTE
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Topics: Animals; Mice, Knockout; Neurons; Synaptic Transmission; Synaptic Vesicles; Synaptogyrins; Synaptophysin
PubMed: 31090538
DOI: 10.7554/eLife.40744 -
Nutritional Neuroscience Sep 2014This study aimed to investigate the protective effect of rutin against trimethyltin-induced spatial learning and memory impairment in mice. This study focused on the...
OBJECTIVES
This study aimed to investigate the protective effect of rutin against trimethyltin-induced spatial learning and memory impairment in mice. This study focused on the role of synaptophysin, growth-associated protein 43 and the action of the dopaminergic system in mechanisms associated with rutin protection and trimethyltin-induced spatial learning and memory impairment.
METHODS
Cognitive learning and memory was measured by Morris Water Maze. The expression of synaptophysin and growth-associated protein 43 in hippocampus was analyzed by western blot. The concentrations of dopamine, homovanillic acid, and dihyroxyphenylacetic acid in hippocampus were detected using reversed phase high-performance liquid chromatography with electrochemical detection.
RESULTS
Trimethyltin-induced spatial learning impairment showed a dose-dependent mode. Synaptophysin but not growth-associated protein 43 was decreased in the hippocampus after trimethyltin administration. The concentration of dopamine decreased, while homovanillic acid increased in the hippocampus after trimethyltin administration. Mice pretreated with 20 mg/kg of rutin for 7 consecutive days exhibited improved water maze performance. Moreover, rutin pretreatment reversed the decrease of synaptophysin expression and dopamine alteration.
DISCUSSION
These results suggest that rutin may protect against spatial memory impairment induced by trimethyltin. Synaptophysin and the dopaminergic system may be involved in trimethyltin-induced neuronal damage in hippocampus.
Topics: Animals; Dopamine; GAP-43 Protein; Hippocampus; Learning; Male; Maze Learning; Memory; Memory Disorders; Mice; Mice, Inbred BALB C; Protective Agents; Rutin; Synaptophysin; Trimethyltin Compounds
PubMed: 24001577
DOI: 10.1179/1476830513Y.0000000085 -
Romanian Journal of Morphology and... 2017The aim of this study is to assess the status of synapses in normal colorectal tissue compared to neoplastic colorectal tissue, and to correlate this status with...
The aim of this study is to assess the status of synapses in normal colorectal tissue compared to neoplastic colorectal tissue, and to correlate this status with survival in patients with colorectal neoplasia. Our study included 61 patients diagnosed with colorectal adenocarcinoma, representing the study group, and 53 patients diagnosed with benign conditions, that required a resection of a colorectal segment, representing the control group. We performed the immunohistochemical staining by using anti-synaptophysin antibody, which identifies synaptic vesicles and, so, we managed to analyze the expression of synapses in colorectal adenocarcinoma. Regarding both the signal area and integrated optical density (IOD) of the synaptophysin, the univariate analysis with a log-rank (Mantel-Cox) test indicated that patients with a low level of synaptophysin had a better overall survival rate than those with a high-level synaptophysin. Also, we noticed that tumor size, tumor invasion and lymph node metastasis were significantly associated with the overall survival rate, whereas the other clinicopathological features were not. In conclusion, the status of synaptic vesicles evaluated via synaptophysin expression in patients with colorectal cancer positively correlates with the survival rate and it can play a role in the neoplastic therapy process.
Topics: Colorectal Neoplasms; Female; Humans; Male; Prognosis; Survival Rate; Synaptophysin
PubMed: 29556635
DOI: No ID Found -
Journal of Alzheimer's Disease : JAD 2014Adults with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by 40 years of age. Synaptophysin (SYN) consistently declines with age and is further...
Adults with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by 40 years of age. Synaptophysin (SYN) consistently declines with age and is further reduced with sporadic AD. Thus, we hypothesized that SYN would be reduced in DS with AD. The gene for synaptojanin-1 (SYNJ1), involved in synaptic vesicle recycling, is on chromosome 21. We measured SYN and SYNJ1 in an autopsy series of 39 cases with DS and 28 without DS, along with 7 sporadic AD cases. SYN was significantly lower in DSAD compared with DS alone and similar to sporadic AD. Reduced SYN is associated with AD neuropathology and with Aβ levels in DS, as is seen in sporadic AD. SYNJ1 was significantly higher in DS and correlated with several measures of Aβ. SYNJ1 was higher in DSAD and significantly higher than SYNJ1 in sporadic AD. Although significantly higher in DS, SYNJ1 is further increased with AD neuropathology suggesting interesting differences in a synapse-associated protein that is overexpressed in trisomy 21.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Autopsy; Brain; Child; Child, Preschool; Down Syndrome; Female; Humans; Infant; Male; Middle Aged; Nerve Tissue Proteins; Phosphoric Monoester Hydrolases; Synaptophysin; Young Adult
PubMed: 24927707
DOI: 10.3233/JAD-140795 -
Scientific Reports Mar 2019Central sprouting of nociceptive afferents in response to neural injury enhances excitability of nociceptive pathways in the central nervous system, often causing pain....
Central sprouting of nociceptive afferents in response to neural injury enhances excitability of nociceptive pathways in the central nervous system, often causing pain. A reliable quantification of central projections of afferent subtypes and their synaptic terminations is essential for understanding neural plasticity in any pathological condition. We previously characterized central projections of cutaneous nociceptive A and C fibers, selectively labeled with cholera toxin subunit B (CTB) and Isolectin B4 (IB4) respectively, and found that they expressed a general synaptic molecule, synaptophysin, largely depending on afferent subtypes (A vs. C fibers) across thoracic dorsal horns. The current studies extended the central termination profiles of nociceptive afferents with synaptoporin, an isoform of synaptophysin, known to be preferentially expressed in C fibers in lumbar dorsal root ganglions. Our findings demonstrated that synaptophysin was predominantly expressed in both peptidergic and IB4-binding C fiber populations in superficial laminae of the thoracic dorsal horn. Cutaneous IB4-labeled C fibers showed comparable expression levels of both isoforms, while cutaneous CTB-labeled A fibers exclusively expressed synaptophysin. These data suggest that central expression of synaptophysin consistently represents synaptic terminations of projecting afferents, at least in part, including nociceptive A-delta and C fibers in the dorsal horn.
Topics: Animals; Female; Immunohistochemistry; Microscopy, Confocal; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Nociceptors; Rats; Rats, Long-Evans; Spinal Cord; Spinal Cord Dorsal Horn; Synaptophysin
PubMed: 30862809
DOI: 10.1038/s41598-019-40967-y -
Journal of Chemical Neuroanatomy Mar 2019Fornix deep brain stimulation (DBS) has the ability to refurbish memory functions in animal models with experimental dementia. One of the possible underlying mechanisms...
Fornix deep brain stimulation (DBS) has the ability to refurbish memory functions in animal models with experimental dementia. One of the possible underlying mechanisms is the acute increase of acetylcholine in the hippocampus. Another suggested hypothesis is neuroplasticity. Recent work in rats has shown that acute fornix DBS can modulate neurotrophic factors as well as synaptic plasticity markers on the short-term. Here, we want to test the hypothesis that acute fornix DBS can also lead to long-term effects on neuroplasticity. Rats received DBS at 100 Hz, 100 μA and 100 μs pulse width for 4 h with electrodes placed bilaterally in the fornix. Seven weeks after stimulation, rats were sacrificed. BDNF, p-CREB, SV2 and synaptophysin immunohistochemistry was performed for their brains. No differences were found in the number of BDNF, p-CREB or SV2 positive cells for fornix DBS rats when compared to sham. Surprisingly, the density of synaptophysin immunoreactive presynaptic boutons was significantly decreased in the CA1 and CA3 subregion of the hippocampus for DBS rats. Therefore, fornix DBS might induce long-term depression related mechanisms.
Topics: Animals; Deep Brain Stimulation; Fornix, Brain; Hippocampus; Long-Term Synaptic Depression; Rats; Rats, Sprague-Dawley; Synaptophysin
PubMed: 30529072
DOI: 10.1016/j.jchemneu.2018.12.001 -
The European Journal of Neuroscience Apr 2010Although behavioral lateralization is known to correlate with certain aspects of brain asymmetry in primates, there are limited data concerning hemispheric biases in the...
Although behavioral lateralization is known to correlate with certain aspects of brain asymmetry in primates, there are limited data concerning hemispheric biases in the microstructure of the neocortex. In the present study, we investigated whether there is asymmetry in synaptophysin-immunoreactive puncta density and protein expression levels in the region of hand representation of the primary motor cortex in chimpanzees (Pan troglodytes). Synaptophysin is a presynaptic vesicle-associated protein found in nearly all synapses of the central nervous system. We also tested whether there is a relationship between hand preference on a coordinated bimanual task and the interhemispheric distribution of synaptophysin as measured by both stereologic counts of immunoreactive puncta and by Western blotting. Our results demonstrated that synaptophysin-immunoreactive puncta density is not asymmetric at the population level, whereas synaptophysin protein expression levels are significantly higher in the right hemisphere. Handedness was correlated with interindividual variation in synaptophysin-immunoreactive puncta density. As a group, left-handed and ambidextrous chimpanzees showed a rightward bias in puncta density. In contrast, puncta densities were symmetrical in right-handed chimpanzees. These findings support the conclusion that synapse asymmetry is modulated by lateralization of skilled motor behavior in chimpanzees.
Topics: Animals; Blotting, Western; Female; Functional Laterality; Hand; Immunohistochemistry; Male; Motor Activity; Motor Cortex; Neocortex; Pan troglodytes; Synaptophysin
PubMed: 20384782
DOI: 10.1111/j.1460-9568.2010.07168.x -
Physiology & Behavior Feb 2022Sexually naïve female mice do not display high levels of sexual receptivity in their first sexual experience; they require around 4-5 sexual encounters to display the...
Sexually naïve female mice do not display high levels of sexual receptivity in their first sexual experience; they require around 4-5 sexual encounters to display the full receptive response, assessed by the lordosis reflex. In this study, we evaluated if repeated sexual stimulation with the same male is associated with changes in synaptic remodeling evaluated by synaptophysin (SYP) in brain structures involved in the control of sexual behavior such as the main and accessory olfactory bulbs (MOB and AOB, respectively), medial preoptic area (MPOA), ventromedial hypothalamus (VMH), and amygdala (AMG). Female mice were ovariectomized and hormonally primed to induce sexual receptivity. They were randomly distributed into three groups: a) sexually naïve (SN), with no prior sexual stimulation; b) sexually inexperienced (SI), with one prior mating session; and c) sexually experienced (SE), with six mating sessions. The SI group showed a significant decrease in SYP in the glomerular, mitral and granular layers of the AOB in comparison to SN and SE females. SYP expression increased in the SE group in comparison to SN and SI females in the glomerular and mitral cell layers of the AOB. No significant differences between groups were found in the other brain regions (MOB, MPOA, VMH or AMG). These changes in SYP expression in the AOB suggest that plastic modifications in this brain region can be associated with receptivity increase in sexual experience in female mice.
Topics: Animals; Female; Hypothalamus; Male; Mice; Olfactory Bulb; Preoptic Area; Sexual Behavior, Animal; Synaptophysin
PubMed: 34798129
DOI: 10.1016/j.physbeh.2021.113649 -
The Biochemical Journal Jun 2007Biogenesis and recycling of synaptic vesicles are accompanied by sorting processes that preserve the molecular composition of the compartments involved. In the present...
Biogenesis and recycling of synaptic vesicles are accompanied by sorting processes that preserve the molecular composition of the compartments involved. In the present study, we have addressed the targeting of synaptobrevin 2/VAMP2 (vesicle-associated membrane protein 2), a critical component of the synaptic vesicle--fusion machinery, in a heterotypic context where its sorting is not confounded by the presence of other neuron-specific molecules. Ectopically expressed synaptophysin I interacts with VAMP2 and alters its default surface targeting to a prominent vesicular distribution, with no effect on the targeting of other membrane proteins. Protein-protein interaction is not sufficient for the control of VAMP2 sorting, which is mediated by the C-terminal domain of synaptophysin I. Synaptophysin I directs the sorting of VAMP2 to vesicles before surface delivery, without influencing VAMP2 endocytosis. Consistent with this, dynamin and alpha-SNAP (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein) mutants which block trafficking at the plasma membrane do not abrogate the effect of synaptophysin I on VAMP2 sorting. These results indicate that the sorting determinants of synaptic vesicle proteins can operate independently of a neuronal context and implicate the association of VAMP2 with synaptophysin I in the specification of the pathway of synaptic vesicle biogenesis.
Topics: Animals; Cell Membrane; Dynamins; Exocytosis; HeLa Cells; Humans; Neurons; Protein Transport; Recombinant Fusion Proteins; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; Subcellular Fractions; Synaptophysin; Vesicle-Associated Membrane Protein 2
PubMed: 17331077
DOI: 10.1042/BJ20061907