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Brain Research Mar 2022Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of...
Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of neurons in the neocortical white matter in TLE patients than in controls. The aim of this work was to investigate whether white matter neurons are part of the neuronal circuitry. Therefore, we studied the distribution and density of synapses in surgically resected neocortical tissue of pharmacotherapy-resistant TLE patients. Neocortical white matter of temporal lobe from non-epileptic patients were used as controls. Synapses and neurons were visualized with immunohistochemistry using antibodies against synaptophysin and NeuN, respectively. The presence of synaptophysin in presynaptic terminals was verified by electron microscopy. Quantification of immunostaining was performed and the data of the patients' cognitive tests as well as clinical records were compared to the density of neurons and synapses. Synaptophysin density in the white matter of TLE patients was significantly higher than in controls. In TLE, a significant correlation was found between synaptophysin immunodensity and density of white matter neurons. Neuronal as well as synaptophysin density significantly correlated with scores of verbal memory of TLE patients. Neurosurgical outcome of TLE patients did not significantly correlate with histological data, although, higher neuronal and synaptophysin densities were observed in patients with favorable post-surgical outcome. Our results suggest that white matter neurons in TLE patients receive substantial synaptic input and indicate that white matter neurons may be integrated in epileptic neuronal networks responsible for the development or maintenance of seizures.
Topics: Drug Resistant Epilepsy; Epilepsy, Temporal Lobe; Humans; Neocortex; Nerve Net; Neurons; Synapses; Synaptophysin; Verbal Learning; White Matter
PubMed: 35041843
DOI: 10.1016/j.brainres.2022.147787 -
Scientific Reports May 2021Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4)...
Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.
Topics: Adenosine Triphosphate; Animals; Astrocytes; Cells, Cultured; Cerebral Cortex; Electron Transport Complex I; Hippocampus; Male; Mice; Mice, Knockout; Mitochondria; Nerve Tissue Proteins; Neurites; Neurons; Organ Specificity; Synaptophysin
PubMed: 34040028
DOI: 10.1038/s41598-021-90127-4 -
European Review For Medical and... Mar 2021Pancreatic neuroendocrine tumors (pNETs) are neuroendocrine tumors primarily found in the pancreas and upper small intestine. There are ten different pNETs: nine of...
Pancreatic neuroendocrine tumors (pNETs) are neuroendocrine tumors primarily found in the pancreas and upper small intestine. There are ten different pNETs: nine of these are associated with a specific functional syndrome, while one is not associated with a specific hormonal syndrome, and it is called non-functional. Up to 90% of pNETs are classified as non-functional. Immunohistochemistry is essential to define the diagnosis. However, to have a correct and reliable diagnosis, the pathologist must have adequately collected and treated tissue samples, thus the surgeon himself should be aware of some fundamental notions about tissue collection and fixation. Although several common biomarkers have been described to date, Chromogranin A and synaptophysin are currently considered the most specific immunohistochemical markers for NETs. Nearly 100% of pNETs are positive for both synaptophysin and Chromogranin A. Therefore, CgA and synaptophysin are effective for well-differentiated NETs but are less helpful in the diagnosis of poorly differentiated NECs, due to dedifferentiation, and then, degranulation of tumor cells. The Neuronal Specific Enolase (NSE) results to be an adequate marker in these cases. Considering the specific markers, many studies reported that endocrine pancreatic neoplasms are able to produce many different polypeptides and amines. Through immunohistochemical techniques, it is possible to define the diagnosis of pNET, which allows the clinicians to direct the patient to an effective therapeutic procedure. But to have a correct and reliable diagnosis, the tissue samples have to be adequately collected and treated.
Topics: Biomarkers, Tumor; Chromogranin A; Humans; Immunohistochemistry; Male; Neuroendocrine Tumors; Pancreatic Neoplasms; Surgeons; Synaptophysin
PubMed: 33829441
DOI: 10.26355/eurrev_202103_25418 -
Journal of Clinical Pathology Sep 1996A case of neurocytoma arising in the rostral pontine region of an 18 year old man is reported. The patient developed a right trochlear nerve palsy and was shown to have...
A case of neurocytoma arising in the rostral pontine region of an 18 year old man is reported. The patient developed a right trochlear nerve palsy and was shown to have a well circumscribed, contrast enhancing mass on magnetic resonance imaging. The tumour was characterised histologically by a uniform population of medium sized round nuclei and slightly eosinophilic cytoplasm or occasional perinuclear halos, with delicate branching capillaries, patches of fibrillary matrix, and occasional perivascular pseudorosettes. Immunohistochemical studies demonstrated strong reactivity for synaptophysin in the fibrillary processes and cytoplasm of tumour cells. The present tumour is an exceptional case of neurocytoma arising in the pons.
Topics: Adolescent; Brain Neoplasms; Humans; Immunohistochemistry; Male; Neurocytoma; Pons; Synaptophysin
PubMed: 9038764
DOI: 10.1136/jcp.49.9.764 -
Investigative Ophthalmology & Visual... May 2023To investigate changes in myofiber composition in the global layer (GL) and orbital layer (OL) of extraocular muscles (EOMs) from terminal amyotrophic lateral sclerosis...
PURPOSE
To investigate changes in myofiber composition in the global layer (GL) and orbital layer (OL) of extraocular muscles (EOMs) from terminal amyotrophic lateral sclerosis (ALS) donors.
METHODS
Medial recti muscles collected postmortem from spinal-onset ALS, bulbar-onset ALS, and healthy control donors were processed for immunofluorescence with antibodies against myosin heavy chain (MyHC) IIa, MyHCI, MyHCeom, laminin, neurofilaments, synaptophysin, acetylcholine receptor γ-subunit, and α-bungarotoxin.
RESULTS
The proportion of myofibers containing MyHCIIa was significantly smaller and MyHCeom was significantly larger in the GL of spinal-onset ALS and bulbar-onset ALS donors compared to control donors. Changes in the GL were more prominent in the bulbar-onset ALS donors, with a significantly larger proportion of myofibers containing MyHCeom being present compared to spinal-onset ALS donors. There were no significant differences in the myofiber composition in the OL. In the spinal-onset ALS donors, the proportions of myofibers containing MyHCIIa in the GL and MyHCeom in the OL were significantly correlated with the disease duration. Neurofilament and synaptophysin were present at motor endplates of myofibers containing MyHCeom in ALS donors.
CONCLUSIONS
The EOMs of terminal ALS donors displayed changes in the fast-type myofiber composition in the GL, with a more pronounced alteration in bulbar-onset ALS donors. Our results align with the worse prognosis and subclinical changes in eye movement function previously observed in bulbar-onset ALS patients and suggest that the myofibers in the OL might be more resistant to the pathological process in ALS.
Topics: Humans; Oculomotor Muscles; Amyotrophic Lateral Sclerosis; Synaptophysin; Myosin Heavy Chains; Protein Isoforms
PubMed: 37200039
DOI: 10.1167/iovs.64.5.15 -
BMC Anesthesiology Nov 2017Previous studies have shown that cyclooxygenase-2, a key enzyme that converts arachidonic acid to prostaglandins, is involved in anxiety and cognitive processes, but few...
BACKGROUND
Previous studies have shown that cyclooxygenase-2, a key enzyme that converts arachidonic acid to prostaglandins, is involved in anxiety and cognitive processes, but few studies have investigated the effects of chronic administration of cyclooxygenase-2 inhibitors on anxiety, learning and memory under normal physiological conditions. The aim of the study was to investigate the effects of chronic administration of parecoxib, a cyclooxygenase-2 inhibitor, on anxiety behavior and memory performance under normal physiological conditions and to explore the possible neural mechanism underlying parecoxib-mediated effects.
METHODS
Adult male ICR mice were randomly divided into four groups: the control group and three parecoxib groups. Mice received normal saline or parecoxib (2.5, 5.0 or 10 mg/kg) intraperitoneal injection once a day for 21 days, respectively. Elevated plus-maze, novel object recognition and Y maze tests were conducted on day 23, 24 and 26, respectively. Four additional groups that received same drug treatment were used to measure synaptophysin protein levels by western blot and prostaglandin E2 (PGE2) levels by ELISA in the amygdala and hippocampus on day 26.
RESULTS
Chronic parecoxib exerted an anxiolytic-like effect in the plus-maze test test, and enhanced memory performance in the novel object recognition and Y maze tests. Western blot analysis showed that chronic parecoxib down-regulated synaptophysin levels in the amygdala and up-regulated synaptophysin levels in the hippocampus. ELISA assay showed that chronic parecoxib inhibited PGE2 in the hippocampus but not amygdala.
CONCLUSIONS
Chronic parecoxib exerts anxiolytic-like and memory enhancing effects, which might be mediated through differential modulation of synaptophysin and PGE2 in the amygdala and hippocampus.
Topics: Animals; Anti-Anxiety Agents; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Gene Expression; Hippocampus; Isoxazoles; Male; Maze Learning; Mice; Mice, Inbred ICR; Nootropic Agents; Random Allocation; Synaptophysin
PubMed: 29132299
DOI: 10.1186/s12871-017-0443-y -
Biochemical Society Transactions Dec 2005The integral SV (synaptic vesicle) protein synaptophysin was one of the first nerve terminal proteins identified. However its role, if any, in the SV life cycle remains... (Review)
Review
The integral SV (synaptic vesicle) protein synaptophysin was one of the first nerve terminal proteins identified. However its role, if any, in the SV life cycle remains undetermined. One of the most prominent features of synaptophysin is that its cytoplasmic C-terminus largely consists of pentapeptide repeats initiated by a tyrosine residue. Synaptophysin is heavily phosphorylated by tyrosine kinases in the nerve terminal, suggesting that this phosphorylation is central to its function. This review will cover the evidence for tyrosine phosphorylation of synaptophysin and how this phosphorylation may control its function in the SV life cycle.
Topics: Amino Acid Sequence; Animals; Endocytosis; Molecular Sequence Data; Neuronal Plasticity; Phosphorylation; Protein Kinases; Sequence Alignment; Synaptic Vesicles; Synaptophysin; Tyrosine
PubMed: 16246116
DOI: 10.1042/BST0331350 -
Journal of Anatomy Jan 2021Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial...
Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end-nets and flower-spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double-labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high-resolution maps of the rat subendocardial neural plexus at the cavo-atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo-atrial junction than the mid-atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post-ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower-spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.
Topics: Animals; Autonomic Nervous System; Calcitonin Gene-Related Peptide; Choline O-Acetyltransferase; Heart; Immunohistochemistry; Nerve Fibers; Rats; Sensory Receptor Cells; Synaptophysin; Tyrosine 3-Monooxygenase
PubMed: 32783212
DOI: 10.1111/joa.13284 -
The Anatomical Record. Part A,... Sep 2004Liver progenitor cells as well as hepatic stellate cells have neuroendocrine features. Progenitor cells express chromogranin-A and neural cell adhesion molecule,... (Review)
Review
Liver progenitor cells as well as hepatic stellate cells have neuroendocrine features. Progenitor cells express chromogranin-A and neural cell adhesion molecule, parathyroid hormone-related peptide, S-100 protein, neurotrophins, and neurotrophin receptors, while hepatic stellate cells express synaptophysin, glial fibrillary acidic protein, neural cell adhesion molecule, nestin, neurotrophins, and their receptors. This phenotype suggests that these cell types form a neuroendocrine compartment of the liver, which could be under the control of the central nervous system. We recently showed that the parasympathetic nervous system promotes progenitor cell expansion after liver injury, since selective vagotomy reduces the number of progenitor cells after chemical injury in the rat. Similarly, after transplantation, which surgically denervates the liver, human livers that develop hepatitis have fewer progenitor cells than native, fully innervated livers with similar degrees of liver injury. There is also accumulating experimental evidence linking the autonomic system, in particular the sympathetic nervous system (SNS), with the pathogenesis of cirrhosis and its complications. Recently, it has been shown that hepatic stellate cells themselves respond to neurotransmitters. Moreover, inhibition of the SNS reduced fibrosis in carbon tetrachloride-induced liver injury. In view of the denervated state of transplanted livers, it is very important to unravel the neural control mechanisms of regeneration and fibrogenesis. Moreover, since there is a shortage of donor organs, a better understanding of the mechanisms of regeneration could have therapeutic possibilities, which could even obviate the need for orthotopic liver transplantation.
Topics: Autonomic Nervous System; Hepatocytes; Humans; Liver; Liver Regeneration; Models, Neurological; Neurosecretory Systems; Neurotransmitter Agents; Stem Cells; Synaptophysin
PubMed: 15382010
DOI: 10.1002/ar.a.20096 -
Journal of Anatomy Aug 2023Chemical and electrical synapses (gap junctions) are widely prevalent in the nervous system. Gap junctions emerge long before chemical synapses, allowing communication...
Chemical and electrical synapses (gap junctions) are widely prevalent in the nervous system. Gap junctions emerge long before chemical synapses, allowing communication between developing cells, and are thought to be involved in establishing neural circuits. Mounting evidence indicates that these two modalities of synaptic transmission closely interact during retinal development and that such interactions play a critical role in synaptogenesis and circuit formation during the perinatal period. In vertebrates, gap junctions consist of two connexins which in turn are made up of six connexins (Cx). To what extent Cx45 and Cx36, the most abundant connexins in the retina, are involved in synaptogenesis and retinal circuit formation is not known. The here presented immunohistochemical study used stainings of Cx45, Cx36 and Synaptophysin in the outer and inner (IPL) plexiform layers of postnatal day 8-16 mice retinas to shed light on the role of connexins during critical neuronal developmental processes. Cx45 and Cx36 expressions in both plexiform layers of the mouse retina increased till eye opening and dropped afterwards. The percentage of heterotypic Cx45/Cx36 gap junctions is also higher before the critical event of eye opening. Finally, Cx45 is closely located and/or colocalized with Synaptophysin also shortly before eye opening in the IPL of the mouse retina. All findings point towards a pivotal role for Cx45 during postnatal synaptogenesis in the mouse retina. However, a more functional study is needed to determine the role of Cx45 during synaptogenesis and circuit formation.
Topics: Animals; Mice; Connexins; Gap Junctions; Neurons; Retina; Synaptophysin
PubMed: 35315057
DOI: 10.1111/joa.13651