Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development.
- Keywords
- Anti-NMDAR encephalitis, BDNF, Dendritic branching, Neuronal development, Synaptic proteins,
- MeSH
- Dendrites * drug effects metabolism MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Membrane Proteins metabolism immunology MeSH
- Brain-Derived Neurotrophic Factor * metabolism MeSH
- Neurons * metabolism drug effects MeSH
- Disks Large Homolog 4 Protein metabolism MeSH
- Nerve Tissue Proteins immunology metabolism MeSH
- Receptors, N-Methyl-D-Aspartate * immunology MeSH
- Synaptophysin metabolism MeSH
- Carrier Proteins MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- gephyrin MeSH Browser
- Membrane Proteins MeSH
- Brain-Derived Neurotrophic Factor * MeSH
- Disks Large Homolog 4 Protein MeSH
- Nerve Tissue Proteins MeSH
- Receptors, N-Methyl-D-Aspartate * MeSH
- Synaptophysin MeSH
- Carrier Proteins MeSH
Solitary fibrous tumors (SFTs) may show unusual morphologies, and in such circumstances, an unexpected immunoprofile can be misleading. Following an index case of myxoid meningeal SFT with a neuroendocrine immunoprofile, we decided to assess a neuroendocrine profile in SFTs from various locations. The cohort of 9 meningeal and 28 extrameningeal SFTs was evaluated for CNS WHO grade (G1-G3) and 4-tiered Demicco risk stratification. Immunohistochemical detection of synaptophysin, chromogranin, INSM1, CD56, and CD57 was performed in each case and semiquantitatively assessed (0: no expression; 1+: <10% positive; 2+: 11-50%; and 3+: >51%); whole sections (meningeal SFTs) or tissue microarray (extrameningeal SFTs) were used for immunohistochemistry. The cohort included 13 men and 24 women. Meningeal SFTs included 5 WHO G1, 3 WHO G2, and 1 WHO G3 tumors. Extrameningeal SFTs included 21 low-risk, 4 intermediate-risk, and 2 high-risk tumors. INSM1 immunoreactivity was observed in 12 of 37 cases (32%; 8 cases 1+, 3 cases 2+, and 1 case 3+); synaptophysin was positive in 6 of 35 cases (19%; 5 cases 1+ and 1 case 2+); CD56 was positive in 20 of 37 cases (54%; 16 cases 1+, 3 cases 2+, and 1 case 3+); and CD57 was expressed in 14 of 36 cases (39%; 5 cases 1+, 4 cases 2+, and 5 cases 3+). Chromogranin positivity was not observed. No significant association was observed between expression of neuroendocrine markers and tumor grade, Demicco risk group or meningeal and extrameningeal location. Extrapleural SFTs showed a tendency for positivity of INSM1 (P = .014, χ2) and CD57 (P = .017, χ2) compared to pleural SFTs.
- Keywords
- INSM1, Neuroendocrine, Soft tissue tumors, Solitary fibrous tumor, Synaptophysin,
- MeSH
- Chromogranins MeSH
- Humans MeSH
- Meningeal Neoplasms * diagnosis pathology MeSH
- Biomarkers, Tumor metabolism MeSH
- Soft Tissue Neoplasms * MeSH
- Neuroendocrine Tumors * MeSH
- Repressor Proteins metabolism MeSH
- Solitary Fibrous Tumors * diagnosis pathology MeSH
- Synaptophysin metabolism MeSH
- Severe Fever with Thrombocytopenia Syndrome * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Chromogranins MeSH
- INSM1 protein, human MeSH Browser
- Biomarkers, Tumor MeSH
- Repressor Proteins MeSH
- Synaptophysin MeSH
The kinetics of the phasic synchronous and delayed asynchronous release of acetylcholine quanta was studied at the neuromuscular junctions of aging rats from infant to mature animals at various frequencies of rhythmic stimulation of the motor nerve. We found that in infants 6 (P6) and 10 (P10) days after birth a strongly asynchronous phase of quantal release was observed, along with a reduced number of quanta compared to the synapses of adults. The rise time and decay of uni-quantal end-plate currents were significantly longer in infant synapses. The presynaptic immunostaining revealed that the area of the synapses in infants was significantly (up to six times) smaller than in mature junctions. The intensity of delayed asynchronous release in infants increased with the frequency of stimulation more than in adults. A blockade of the ryanodine receptors, which can contribute to the formation of delayed asynchronous release, had no effect on the kinetics of delayed secretion in the infants unlike synapses of adults. Therefore, high degree of asynchrony of quantal release in infants is not associated with the activity of ryanodine receptors and with the liberation of calcium ions from intracellular calcium stores.
- Keywords
- Developing neuromuscular junction, Kinetics of quantum release, Ryanodine receptors, Synaptic latency,
- MeSH
- Bungarotoxins pharmacokinetics MeSH
- Electric Stimulation MeSH
- Rats MeSH
- Gallic Acid analogs & derivatives pharmacokinetics MeSH
- Neuromuscular Junction drug effects growth & development metabolism MeSH
- Neurotransmitter Agents metabolism MeSH
- Receptors, Nicotinic metabolism MeSH
- Animals, Newborn MeSH
- Reaction Time physiology MeSH
- Ryanodine pharmacokinetics MeSH
- Synaptic Potentials physiology MeSH
- Synaptophysin metabolism MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate MeSH Browser
- Bungarotoxins MeSH
- Gallic Acid MeSH
- Neurotransmitter Agents MeSH
- Receptors, Nicotinic MeSH
- Ryanodine MeSH
- Synaptophysin MeSH
The study involved histological and immunohistochemical examinations of the adrenal glands of healthy slaughtered cattle. Glands of 13 bulls, 10 heifers and 10 cows were examined. The following histological findings were observed: Unequal thickness of connective capsule and nodular formations of the zona glomerulosa (ZG), eosinophilic granules in cells of the ZG, globoid arrangement of the zona fasciculata, nodules or pegs of cortical tissue in the medulla, mutual interlacing of superficial and deep zones of the medulla, proliferation of cortical or medullary cells into the blood vessels wall situated in the medulla and focal inflammatory infiltrates. Cortical cells and noradrenalin-secreting (N) cells in the medulla expressed cytoplasmic positivity of S100 protein. Both adrenalin (A) cells and N cells were positive in synaptophysin. The majority of the cells in the cortex and in the medulla displayed were positive for chromogranin A. Electron microscopy showed structureless, electrondense particles of varying size and shape, mostly displaying the having mostly character of secretory granules.
- MeSH
- Epinephrine metabolism MeSH
- Blood Vessels anatomy & histology MeSH
- Chromogranin A analysis MeSH
- Adrenal Medulla anatomy & histology blood supply chemistry MeSH
- Microscopy, Electron MeSH
- Fluorescent Antibody Technique MeSH
- Norepinephrine metabolism MeSH
- Secretory Vesicles MeSH
- Cattle anatomy & histology MeSH
- Synaptophysin analysis MeSH
- Zona Fasciculata anatomy & histology chemistry MeSH
- Zona Glomerulosa anatomy & histology chemistry MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Cattle anatomy & histology MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Epinephrine MeSH
- Chromogranin A MeSH
- Norepinephrine MeSH
- Synaptophysin MeSH
We report a case of a 73-year-old female with a rare simultaneous occurrence of three tumors: ovarian carcinoma, endometrial carcinoma, and breast carcinoma. The ovarian tumor was a primary pure large-cell neuroendocrine carcinoma. Grossly, the left ovary was enlarged by a solid tumor that measured 9 x 7 x 7 cm. Histologically, the tumor consisted of large cells with irregular hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm. In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was cribriform and solid-alveolar, with palisaded tumor cells located peripherally. The tumor cells showed multiple mitotic figures (up to 43 mitoses/10 HPF). Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for EMA, synaptophysin, chromogranin, CD56, and CEA. Cytokeratin 20 was positive focally. Primary large-cell neuroendocrine carcinoma of the ovary is a rare tumor. To the best of our knowledge, only 4 cases of a pure tumor of this type have been reported to date.
- MeSH
- CD56 Antigen analysis MeSH
- Chromogranins analysis MeSH
- Immunohistochemistry MeSH
- Carcinoembryonic Antigen analysis MeSH
- Humans MeSH
- Neoplasms, Multiple Primary * MeSH
- Endometrial Neoplasms pathology MeSH
- Brain Neoplasms chemistry immunology secondary therapy MeSH
- Breast Neoplasms pathology MeSH
- Ovarian Neoplasms chemistry immunology pathology therapy MeSH
- Carcinoma, Neuroendocrine chemistry immunology secondary therapy MeSH
- Aged MeSH
- Synaptophysin analysis MeSH
- Carcinoma, Large Cell chemistry immunology secondary therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Names of Substances
- CD56 Antigen MeSH
- Chromogranins MeSH
- Carcinoembryonic Antigen MeSH
- Synaptophysin MeSH
The aortic bodies are small paraganglia distributed along the vagus nerve and its branches in the vicinity of the aortic arch which, like the carotid bodies, act as arterial chemoreceptors. In the rat carotid body, corelease of ATP and acetylcholine (ACh) from glomus cells is considered to be the main mechanism mediating fast hypoxic chemotransmission while dopamine, serotonin, and nitric oxide (NO) exert modulating effects. The present study was aimed at determination of the endogenous sources of serotonin, ACh and NO within rat and guinea pig aortic bodies by immunohistochemical double- and triple-labeling approaches, utilizing antibodies to serotonin, the NO and ACh synthesizing enzymes neuronal NO synthase (nNOS) and choline acetyltransferase (ChAT), respectively, as well as to the vesicular acetylcholine transporter (VAChT). Additional marker antibodies were directed against the rate-limiting enzyme of catecholamine synthesis, i.e. tyrosine hydroxylase (TH), and the vesicular protein, synaptophysin (SYN). In both species, all aortic body glomus cells were immunoreactive to serotonin and cholinergic markers. In the rat, all glomus cells were additionally catecholaminergic, as indicated by TH-immunoreactivity, whereas this applied only to a subgroup of guinea pig glomus cells. On the other hand, all guinea pig glomus cells were nNOS-immunoreactive, whereas only nerve fibers but not glomus cells exhibited nNOS-immunoreactivity in the rat. These data support the concept that the chemoexcitatory transmitters ACh and serotonin are involved in hypoxic excitation of aortic chemoreceptor terminals in both species. The production of the inhibitory modulators, dopamine and NO, however, appears to be species-specifically regulated.
- MeSH
- Acetylcholine metabolism MeSH
- Adenosine Triphosphate metabolism MeSH
- Choline O-Acetyltransferase metabolism MeSH
- Aortic Bodies cytology metabolism MeSH
- Immunohistochemistry MeSH
- Carotid Body metabolism MeSH
- Catecholamines metabolism MeSH
- Rats MeSH
- Membrane Transport Proteins metabolism MeSH
- Guinea Pigs MeSH
- Rats, Wistar MeSH
- Serotonin metabolism MeSH
- Synaptophysin metabolism MeSH
- Nitric Oxide Synthase metabolism MeSH
- Tyrosine 3-Monooxygenase metabolism MeSH
- Vesicular Acetylcholine Transport Proteins MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Guinea Pigs MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholine MeSH
- Adenosine Triphosphate MeSH
- Choline O-Acetyltransferase MeSH
- Catecholamines MeSH
- Membrane Transport Proteins MeSH
- Serotonin MeSH
- Slc18a3 protein, rat MeSH Browser
- Synaptophysin MeSH
- Nitric Oxide Synthase MeSH
- Tyrosine 3-Monooxygenase MeSH
- Vesicular Acetylcholine Transport Proteins MeSH
The group of 35 carcinoid tumours obtained from 34 patients was reviewed according to recent histopathological criteria. Consequently, evaluation of the Grimelius staining and immunohistochemical detection of chromogranin A (CgA), Leu-7 (CD-57), synaptophysin, neuron-specific enolase (NSE), (beta-III tubulin, Ki-67 and proliferating cell nuclear antigen (PCNA) was performed. The majority of tumours (29, i.e. 83%) were classified as typical carcinoids composed predominantly of mixed solid and trabecular or solid and tubular growth patterns. Six tumours (17%) revealed more prominent cytological abnormalities corresponding with the diagnosis of atypical carcinoid. The majority of tumours (31, i.e. 93.9%) showed granular cytoplasmic positivity in Grimelius staining and diffuse cytoplasmic positivity of NSE (34, i.e. 97.1%). All of the 32 stained tumour samples showed positive immunoreactivity for synaptophysin. A high percentage of tumours (32, i.e. 91.4%) revealed also a positive reaction with antibody TU-20 detecting (beta-III tubulin, a marker of an early stage of neuronal differentiation. Thirty-four tumours (97.1%) showed granular cytoplasmic positivity for both markers of neuroendocrine granules (CgA and Leu-7). One tumour (2.9%) was positive only for Leu-7. Tumour cells revealed predominantly low proliferative activity evaluated by PCNA and Ki-67 immunodetection. Higher degree of proliferation was observed especially in atypical carcinoids.
- MeSH
- Ki-67 Antigen analysis MeSH
- CD57 Antigens analysis MeSH
- Chromogranin A MeSH
- Chromogranins analysis MeSH
- Adult MeSH
- Phosphopyruvate Hydratase analysis MeSH
- Gastrointestinal Neoplasms chemistry diagnosis MeSH
- Immunohistochemistry MeSH
- Carcinoid Tumor chemistry diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Biomarkers, Tumor analysis MeSH
- Proliferating Cell Nuclear Antigen analysis MeSH
- Aged MeSH
- Synaptophysin analysis MeSH
- Tubulin analysis MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ki-67 Antigen MeSH
- CD57 Antigens MeSH
- Chromogranin A MeSH
- Chromogranins MeSH
- Phosphopyruvate Hydratase MeSH
- Biomarkers, Tumor MeSH
- Proliferating Cell Nuclear Antigen MeSH
- Synaptophysin MeSH
- Tubulin MeSH
As in diseases of other (neuro)endocrine glands, the pathology of the islets of Langerhans comprises both states of hypofunction, notably hypoinsulinism,--diabetes mellitus--and those of hyperfunction, such as hyperinsulinism from either nesidiodysplasia ("nesidioblastosis") or genuine islet-cell neoplasms. The pathogenesis of some characteristic structural lesions of these diseases of the islet parenchymal cells is reviewed against their neuroendocrine background, both phylogenetically and ontogenetically. A preliminary report is given of the appearance of argyrophil insulin cells during the normal foetal development of the islet parenchyma of the rabbit. In addition, the distribution of the newly discovered neuroendocrine markers synaptophysin and chromogranin A has been reviewed immunohistochemically in normal and neoplastic islet parenchyma cells; the insulin cells do not seem to contain chromogranin A.
- MeSH
- Chromogranin A MeSH
- Chromogranins physiology MeSH
- Diabetes Mellitus physiopathology MeSH
- Hyperinsulinism physiopathology MeSH
- Rabbits MeSH
- Islets of Langerhans pathology physiopathology MeSH
- Humans MeSH
- Membrane Proteins physiology MeSH
- Neurosecretory Systems physiopathology MeSH
- Synaptophysin MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- CHGA protein, human MeSH Browser
- Chromogranin A MeSH
- Chromogranins MeSH
- Membrane Proteins MeSH
- Synaptophysin MeSH