Search results for "choline"

Cellular distribution in the rat telencephalon of mRNAs encoding for the alpha 3 and alpha 4 subunits of the nicotinic acetylcholine receptor.

1995

Pharmacological and electrophysiological studies provide evidence for the involvement of different nicotinic acetylcholine receptor isoforms in rat neocortical and hippocampal signal transduction. Yet, rather little is known on the cellular localization of these isoforms. With the availability of isoform specific nucleic acid probes and sensitive non-isotopic detection systems, nicotinic receptors can be studied on the mRNA level in individual neurons. In this way, we have paradigmatically studied the distribution of the alpha 3 and alpha 4 isoform mRNAs of the nicotinic receptor in the rat telencephalon. In the cerebral cortex, alpha 3 transcripts were mainly located in pyramidal neurons o…

Expression of the Acetylcholine Receptor α-Subunit Gene is Associated with Paraneoplastic Myasthenia Gravis in Mixed Thymoma

2000

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction [1]. The muscular AChR has been extensively characterized [2], but the etiology of MG is still obscure. Whether the muscular AChR or another (auto)antigen plays a role during the initiation of MG is unknown [3]. The muscular AChR is a pentameric ion channel composed of four different subunits. The α-subunit contains the acetylcholine binding site and the main epitopes recognized by MG autoantibodies [2]. The human muscle AChR α-subunit exists as two isoforms, P3A- and P3A+ [4]. This is a result of alternative splicing of the P3A exon located betwee…

BODIPY dyes functionalized with 2-(2-dimethylaminophenyl)ethanol moieties as selective OFF–ON fluorescent chemodosimeters for the nerve agent mimics …

2014

[EN] Two OFF-ON fluorescent chemodosimeters based on a BODIPY core for the detection of nerve agent mimics have been synthesized. Their reactivity towards diethylcyanophosphonate (DCNP) and diisopropylfluorophosphate (DFP) has been tested in organic and aqueous phase. These chemodosimeters selectively detect the nerve agent mimics with good LODs. The chemodosimeters hold their sensing properties on solid supports, allowing the preparation of a hand held sensing kit. The sensing in solid-liquid phase has been demonstrated. The X-ray structure of compound 2 has been resolved.

Modulatory control by non-competitive agonists of nicotinic cholinergic neurotransmission in the central nervous system

1995

Abstract Several exogenous and endogenous compounds have been discovered that act on nicotinic acetylcholine receptors as non-competitive agonists (NCA) of low efficacy, and probably also as allosteric regulators of the receptor's sensitivity to acetylcholine. Nicotinic NCAs may be viewed as another facet in the increasingly complex picture of vertebrate brain organization, i.e. they may be part of a higher level ‘chemical’ network that overlays the neuronal network of the CNS. Furthermore, exogenous NCAs may provide a new therapeutic approach to Alzheimer's dementia.

The copy number variant involving part of the α7 nicotinic receptor gene contains a polymorphic inversion.

2008

The alpha7 nicotinic acetylcholine receptor gene (CHRNA7) is located at 15q13-q14 in a region that is strongly linked to the P50 sensory gating deficit, an endophenotype of schizophrenia and bipolar disorder. Part of the gene is a copy number variant, due to a duplication of exons 5-10 and 3' sequence in CHRFAM7A, which is present in many but not all humans. Maps of this region show that the two genes are in opposite orientation in the individual mainly represented in the public access human DNA sequence database (Build 36), suggesting that an inversion had occurred since the duplication. We have used fluorescent in situ hybridization to investigate this putative inversion. Analysis of inte…

Mildronate improves cognition and reduces amyloid-β pathology in transgenic Alzheimer's disease mice

2013

Mildronate, a carnitine congener drug, previously has been shown to provide neuroprotection in an azidothymidine-induced mouse model of neurotoxicity and in a Parkinson's disease rat model. The aim of this study was to investigate the effects of mildronate treatment on cognition and pathology in Alzheimer's disease (AD) model mice (APP(SweDI)). Mildronate was administered i.p. daily at 50 or 100 mg/kg for 28 days. At the end of treatment, the animals were behaviorally and cognitively tested, and brains were assessed for AD-related pathology, inflammation, synaptic markers, and acetylcholinesterase (AChE). The data show that mildronate treatment significantly improved animal performance in w…

Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice.

2004

Alzheimer's disease is characterized by amyloid peptide formation and deposition, neurofibrillary tangles, central cholinergic dysfunction, and dementia; however, the relationship between these parameters is not well understood. We studied the effect of amyloid peptide formation and deposition on central cholinergic function in knock-in mice carrying the human amyloid precursor protein (APP) gene with the Swedish/London double mutation (APP-SL mice) which were crossbred with transgenic mice overexpressing normal (PS1wt) or mutated (M146L; PS1mut) human presenilin-1. APP-SLxPS1mut mice had increased levels of Abeta peptides at 10 months of age and amyloid plaques at 14 months of age while AP…

29 Elevated acetylcholine release in the hippocampus of transgenic mice expressing the human acetylcholinesterase

1998

First mitochondrial genome-wide association study with metabolomics.

2021

AbstractIn the era of personalized medicine with more and more patient-specific targeted therapies being used, we need reliable, dynamic, faster and sensitive biomarkers both to track the causes of disease and to develop and evolve therapies during the course of treatment. Metabolomics recently has shown substantial evidence to support its emerging role in disease diagnosis and prognosis. Aside from biomarkers and development of therapies, it is also an important goal to understand the involvement of mitochondrial DNA (mtDNA) in metabolic regulation, aging and disease development. Somatic mutations of the mitochondrial genome are also heavily implicated in age-related disease and aging. The…

Frequencies of pseudocholinesterase variants in Icelanders, Greeks and Pakistanis.

1968

THE formation of the human pseudocholinesterase variants is controlled by at least four alleles at one autosomal locus termed E1 (ref. 1). The four alleles are , , and (refs. 2–5). The heterozygotes have been found in remarkably uniform frequencies, about 3 to 6 per cent, in Caucasians from Europe and North America3,8–11, and also in Australian aborigines12 and Mexican Indians13, but are relatively rare among Negroes11 and Mongoloids10,11,14.