Regulatory factors controlling tick salivary glands (SGs) are direct upstream neural signaling pathways arising from the tick's central nervous system. Here we investigated the cholinergic signaling pathway in the SG of two hard tick species. We reconstructed the organization of the cholinergic gene locus, and then used in situ hybridization to localize mRNA encoding choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in specific neural cells in the Ixodes synganglion. Immunohistochemical staining revealed that cholinergic axonal projections exclusively reached type I acini in the SG of both Ixodes species. In type I acini, the rich network of cholinergic axons terminate within the basolateral infoldings of the lamellate cells. We also characterized two types (A and B) of muscarinic acetylcholine receptors (mAChRs), which were expressed in Ixodes SG. We pharmacologically assessed mAChR-A to monitor intracellular calcium mobilization upon receptor activation. In vivo injection of vesamicol-a VAChT blocker-at the cholinergic synapse, suppressed forced water uptake by desiccated ticks, while injection of atropine, an mAChR-A antagonist, did not show any effect on water volume uptake. This study has uncovered a novel neurotransmitter signaling pathway in Ixodes SG, and suggests its role in water uptake by type I acini in desiccated ticks.

• MeSH
• acinární buňky metabolismus   fyziologie   MeSH
• axony metabolismus   MeSH
• centrální nervový systém metabolismus   MeSH
• cholin-O-acetyltransferasa genetika   metabolismus   MeSH
• cholinergní látky metabolismus   MeSH
• klíště metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• neurony cholinergní metabolismus   fyziologie   MeSH
• neurony metabolismus   MeSH
• signální transdukce genetika   MeSH
• slinné žlázy metabolismus   fyziologie   MeSH
• vezikulární transportní proteiny acetylcholinu genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Cholinergic hypothesis of Alzheimer's disease (AD) is based on the findings that a reduced and/or perturbed cholinergic activity in the central nervous system correlates with cognitive decline in patients with Alzheimer's disease. The hypothesis resulted in the development of centrally-acting agents potentiating cholinergic neurotransmission; these drugs, however, only slowed down the cognitive decline and could not prevent it. Consequently, the perturbation of the central cholinergic signalling has been accepted as a part of the Alzheimer's aetiology but not necessarily the primary cause of the disease. In the present study we have focused on the rs3810950 polymorphism of ChAT (choline acetyltransferase) gene that has not been studied in Czech population before. METHODS: We carried out an association study to test for a relationship between the rs3810950 polymorphism and Alzheimer's disease in a group of 1186 persons; 759 patients with Alzheimer's disease and 427 control subjects. Furthermore, we performed molecular modelling of the terminal domain (1st-126th amino acid residue) of one of the ChAT isoforms (M) to visualise in silico whether the rs3810950 polymorphism (A120T) can change any features of the tertiary structure of the protein which would have a potential to alter its function. RESULTS: The AA genotype of CHAT was associated with a 1.25 times higher risk of AD (p < 0.002) thus demonstrating that the rs3810950 polymorphism can have a modest but statistically significant effect on the risk of AD in the Czech population. Furthermore, the molecular modelling indicated that the polymorphism is likely to be associated with significant variations in the tertiary structure of the protein molecule which may impact its enzyme activity. CONCLUSIONS: Our findings are consistent with the results of the meta-analytical studies of the relationship between rs3810950 polymorphism and AD and provide further material evidence for a direct (primary) involvement of cholinergic mechanisms in the etiopathogenesis of AD, particularly as a factor in cognitive decline and perturbed conscious awareness commonly observed in patients with AD.

• MeSH
• Alzheimerova nemoc genetika   MeSH
• cholin-O-acetyltransferasa genetika   metabolismus   MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Perineuronal nets (PNNs) are extracellular matrix structures surrounding neuronal sub-populations throughout the central nervous system, regulating plasticity. Enzymatically removing PNNs successfully enhances plasticity and thus functional recovery, particularly in spinal cord injury models. While PNNs within various brain regions are well studied, much of the composition and associated populations in the spinal cord is yet unknown. We aim to investigate the populations of PNN neurones involved in this functional motor recovery. Immunohistochemistry for choline acetyltransferase (labelling motoneurones), PNNs using Wisteria floribunda agglutinin (WFA) and chondroitin sulphate proteoglycans (CSPGs), including aggrecan, was performed to characterise the molecular heterogeneity of PNNs in rat spinal motoneurones (Mns). CSPG-positive PNNs surrounded ~70-80% of Mns. Using WFA, only ~60% of the CSPG-positive PNNs co-localised with WFA in the spinal Mns, while ~15-30% of Mns showed CSPG-positive but WFA-negative PNNs. Selective labelling revealed that aggrecan encircled ~90% of alpha Mns. The results indicate that (1) aggrecan labels spinal PNNs better than WFA, and (2) there are differences in PNN composition and their associated neuronal populations between the spinal cord and cortex. Insights into the role of PNNs and their molecular heterogeneity in the spinal motor pools could aid in designing targeted strategies to enhance functional recovery post-injury.

• MeSH
• cholin-O-acetyltransferasa metabolismus   MeSH
• chondroitinsulfát proteoglykany metabolismus   MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• krysa rodu rattus MeSH
• mícha cytologie   metabolismus   MeSH
• motorické neurony cytologie   metabolismus   MeSH
• neuroplasticita MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4-targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of Alzheimer's disease, is accentuated by apoE4. This revealed that levels of the pre-synaptic cholinergic marker, vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are similar in 4-month-old apoE4 and apolipoprotein E3 (apoE3) mice. Both parameters decrease with age. This decrease is, however, significantly more pronounced in the apoE4 mice. The levels of cholinacetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) were similar in the hippocampus of young apoE4 and apoE3 mice and decreased during aging. For ChAT, this decrease was similar in the apoE4 and apoE3 mice, whereas it was more pronounced in the apoE4 mice, regarding their corresponding AChE and BuChE levels. The level of muscarinic receptors was higher in the apoE4 than in the apoE3 mice at 4 months and increased to similar levels with age. However, the relative representation of the M1 receptor subtype decreased during aging in apoE4 mice. These results demonstrate impairment of the evoked release of acetylcholine in hippocampus by apoE4 in 12-month-old mice but not in 4-month-old mice. The levels of ChAT and the extent of the M2 receptor-mediated autoregulation of ACh release were similar in the adult mice, suggesting that the apoE4-related inhibition of hippocampal ACh release in these mice is not driven by these parameters. Evoked ACh release from hippocampal and cortical slices is similar in 4-month-old apoE4 and apoE3 mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12-month-old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show that the hipocampal cholinergic nerve terminals are specifically affected by apoE4 and that this effect is age dependent.

• MeSH
• acetylcholin metabolismus   MeSH
• apolipoprotein E3 genetika   MeSH
• apolipoprotein E4 genetika   metabolismus   MeSH
• cholin-O-acetyltransferasa metabolismus   MeSH
• guanosin 5'-O-(3-thiotrifosfát) farmakologie   MeSH
• hipokampus účinky léků   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• N-methylskopolamin farmakologie   MeSH
• receptory muskarinové metabolismus   MeSH
• tritium metabolismus   MeSH
• věkové faktory MeSH
• vezikulární transportní proteiny acetylcholinu metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Generation of reactive oxygen species significantly contributes to the pathogenesis of acute renal failure (ARF) induced by myoglobin release. Ginsenosides (GS), the principal active ingredients of ginseng, is considered as an extremely good antioxidative composition of Chinese traditional and herbal drugs. The purpose of the present study was to investigate the protective effect of ginsenoside in rats with ARF on the changes of cholinergic nervous system in the kidney as well as on the involvement of mitogen-activated protein kinases (MAPK) in the hypothalamic paraventricular nuclei (PVN). In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced lipid peroxidation, restored the superoxide dismutase (SOD) level. Meanwhile, the obvious increase of choline acetyltransferase-immunoreactivity (ChAT-IR) in the proximal convoluted tubular cells (PCT) was observed by immunohistochemistry in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the hypothalamic paraventricular nuclei. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, reduce the renal oxidative stress, and ginsenoside can also activate the cholinergic system in PCT, simultaneously MAPK signal pathway in the PVN was also activated.

• MeSH
• akutní poškození ledvin chemicky indukované   enzymologie   patologie   prevence a kontrola   MeSH
• antioxidancia aplikace a dávkování   farmakologie   MeSH
• aplikace orální MeSH
• časové faktory MeSH
• cholin-O-acetyltransferasa metabolismus   MeSH
• cytoprotekce MeSH
• fosforylace MeSH
• ginsenosidy aplikace a dávkování   farmakologie   MeSH
• glycerol MeSH
• malondialdehyd metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 1 metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 3 metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nucleus paraventricularis hypothalami účinky léků   enzymologie   MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• proximální tubuly ledvin účinky léků   enzymologie   patologie   MeSH
• signální transdukce účinky léků   MeSH
• superoxiddismutasa metabolismus   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• cholin-O-acetyltransferasa genetika   metabolismus   MeSH
• financování organizované MeSH
• messenger RNA genetika   MeSH
• polymerázová řetězová reakce využití   MeSH
• potkani inbrední LEW MeSH
• potkani Sprague-Dawley MeSH
• receptor muskarinový M2 genetika   metabolismus   MeSH
• regulace genové exprese enzymů genetika   MeSH
• srdeční síně enzymologie   metabolismus   MeSH
• systém hypotalamus-hypofýza fyziologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

BACKGROUND: Chronic renal failure is frequently associated with a high risk of sudden cardiac death due to dysfunction of the autonomic nervous system. The pathogenic mechanisms underlying the parasympathetic cardiac dysautonomia are not fully elucidated yet. METHODS: Chronic renal failure was induced in rats by 5/6 nephrectomy. Blood pressure, resting heart rate and plasma levels of creatinine, urea and asymmetric dimethylarginine (ADMA) were measured. To characterize the parasympathetic innervation of the heart, chronotropic responses to atropine, metipranolol and to vagal stimulation in the absence or presence of ADMA were investigated in vivo. In vitro, chronotropic and inotropic effects of carbachol and ADMA and mRNA expression of muscarinic M2 receptors, high affinity choline transporter (CHT1), vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) were assessed in the isolated cardiac tissues. RESULTS: In 5/6 nephrectomy rats, the resting heart rate was significantly higher and the parasympathetic tone, measured as the effect of atropine after administration of metipranolol was significantly lower than in control animals. Plasma ADMA levels were significantly elevated in the uraemic rats and significantly inversely correlated with the effect of atropine on the heart rate. No differences were revealed in the plasma norepinephrine concentrations, negative chronotropic responses to stimulation of the vagus nerves, chronotropic and inotropic responses to carbachol and the relative expression of M2 receptors, CHT1, VAChT and ChAT. CONCLUSION: The data suggest that cardioacceleration in chronic renal failure is caused by a diminished cardiac parasympathetic tone in the presence of a functionally intact intrinsic cardiac cholinergic signalling system.

• MeSH
• atropin farmakologie   MeSH
• beta blokátory farmakologie   MeSH
• cholin-O-acetyltransferasa genetika   metabolismus   MeSH
• karbachol farmakologie   MeSH
• kardiotonika farmakologie   MeSH
• krysa rodu rattus MeSH
• ledviny chirurgie   metabolismus   účinky léků   MeSH
• messenger RNA genetika   metabolismus   MeSH
• metipranolol farmakologie   MeSH
• nefrektomie MeSH
• nervus vagus fyziologie   účinky léků   MeSH
• noradrenalin metabolismus   MeSH
• parasympatický nervový systém fyziologie   účinky léků   MeSH
• parasympatolytika farmakologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Wistar MeSH
• proteiny nervové tkáně genetika   metabolismus   MeSH
• proteiny přenášející neurotransmitery přes plazmatickou membránu genetika   metabolismus   MeSH
• srdce inervace   MeSH
• srdeční frekvence fyziologie   MeSH
• vezikulární transportní proteiny acetylcholinu genetika   metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• acetylcholin metabolismus   MeSH
• adenosintrifosfát metabolismus   MeSH
• cholin-O-acetyltransferasa metabolismus   MeSH
• corpora paraaortica cytologie   metabolismus   MeSH
• finanční podpora výzkumu jako téma MeSH
• imunohistochemie MeSH
• karotická tělíska metabolismus   MeSH
• katecholaminy metabolismus   MeSH
• membránové transportní proteiny metabolismus   MeSH
• morčata MeSH
• potkani Wistar MeSH
• serotonin metabolismus   MeSH
• synaptofysin metabolismus   MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• tyrosin-3-monooxygenasa metabolismus   MeSH
• vezikulární transportní proteiny MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• zvířata MeSH

• MeSH
• cholin-O-acetyltransferasa genetika   metabolismus   MeSH
• genetická transkripce genetika   účinky záření   MeSH
• hybridomy MeSH
• messenger RNA fyziologie   účinky léků   MeSH
• nervová tkáň genetika   metabolismus   účinky léků   MeSH
• techniky in vitro MeSH
• transportní proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• Klíčová slova
• nutriční deficit,
• MeSH
• acetylcholinesterasa * metabolismus   MeSH
• axonální transport * účinky léků   MeSH
• cholin-O-acetyltransferasa * metabolismus   MeSH
• dospělí MeSH
• ethanol * aplikace a dávkování   farmakologie   krev   MeSH
• ischemie metabolismus   MeSH
• krysa rodu rattus MeSH
• periferní nervy enzymologie   krevní zásobení   MeSH
• potkani Wistar MeSH
• sacharosa aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH