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Alzheimer spinal ChAT

Shawn Albers, Fatima Inthathirath, Sandeep K Gill, Warren Winick-Ng, Ewa Jaworski, Daisy Y L Wong, Robert Gros, R Jane Rylett
Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions...
September 2014: Neurobiology of Disease
Supriti Samantaray, Varduhi H Knaryan, Donald C Shields, Naren L Banik
While multiple molecular mechanisms contribute to midbrain nigrostriatal dopaminergic degeneration in Parkinson's disease (PD), the mechanism of damage in non-dopaminergic sites within the central nervous system, including the spinal cord, is not well-understood. Thus, to understand the comprehensive pathophysiology underlying this devastating disease, postmortem spinal cord tissue samples (cervical, thoracic, and lumbar segments) from patients with PD were analyzed compared to age-matched normal subjects or Alzheimer's disease for selective molecular markers of neurodegeneration and inflammation...
December 2013: Journal of Neurochemistry
Yazhou Li, Srinivasulu Chigurupati, Harold W Holloway, Mohamed Mughal, David Tweedie, Daniel A Bruestle, Mark P Mattson, Yun Wang, Brandon K Harvey, Balmiki Ray, Debomoy K Lahiri, Nigel H Greig
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease...
2012: PloS One
Ji-Seon Seo, In-Sun Baek, Yea-Hyun Leem, Tae-Kyung Kim, Yearin Cho, Soo Min Lee, Yang Hae Park, Pyung-Lim Han
SK-PC-B70M, an oleanolic-glycoside saponins fraction extracted from the root of Pulsatilla koreana, carries active ingredient(s) that protects the cytotoxicity induced by Aβ(1-42) in SK-N-SH cells. It was recently demonstrated that SK-PC-B70M improved scopolamine-induced deficits of memory consolidation and spatial working memory in rats, and reduced Aβ levels and plaque deposition in the brains of the Tg2576 mouse model of Alzheimer disease. In the present study, we investigated whether SK-PC-B70M produces helpful effects on the pathology of the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS)...
January 12, 2011: Brain Research
Sandeep K Gill, Margaret Ishak, Tomas Dobransky, Vahram Haroutunian, Kenneth L Davis, R Jane Rylett
Cholinergic neurons express choline acetyltransferase (ChAT) which synthesizes acetylcholine. We show here for the first time that primate-specific 82-kDa ChAT is expressed in nuclei of cholinergic neurons in human brain and spinal cord; isoform-specific antibodies were used to compare localization patterns and temporal expression of the more abundant 69-kDa ChAT and primate-specific 82-kDa ChAT in necropsy tissues. The 82-kDa ChAT co-localizes with 69-kDa ChAT in well-characterized cholinergic areas, but is also found in the claustrum which does not contain 69-kDa ChAT...
July 2007: Neurobiology of Aging
Yuanyun Xie, Zhibin Yao, Hong Chai, Wai-Man Wong, Wutian Wu
To study the potential role of Alzheimer precursor protein A4 (APP) and beta-amyloid (A/beta) on aging motor neuron survival, expression of APP, A/beta, and choline acetyltransferase (ChaT) were investigated in aged rats after either distal axotomy or root avulsion injury. Approximately 45% in number of total aged spinal motor neuron were normally APP-positive. A/beta-positive neurites were observed normally in the spinal ventral horn of aged rats. After distal axotomy, without apparent neurodegeneration such as cell loss and decreased ChaT-immunoreactivity, increased levels of APP expression were observed in the spinal cords of aged rats post-injury...
August 15, 2003: Journal of Neuroscience Research
K Ikeda, Y Iwasaki, M Kinoshita, S Marubuchi, S Ono
R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino) ethoxy]ethanol hydrochloride (T-588) enhances acetylcholine release from the frontal cortex and hippocampus in rats, and can ameliorate cognitive dysfunction in various amnesia models of rodents. T-588 protects rat cerebellar granule cells from glutamate neurotoxicity in culture. This agent also inhibits facilitation in the crayfish neuromuscular junction and mammalian cerebellum. Clinical trials of T-588 are underway in patients with Alzheimer's disease...
March 6, 2000: Brain Research
Y Oda
Choline acetyltransferase (ChAT), the enzyme responsible for the biosynthesis of acetylcholine, is presently the most specific indicator for monitoring the functional state of cholinergic neurones in the central and peripheral nervous systems. ChAT is a single-strand globular protein. The enzyme is synthesized in the perikaryon of cholinergic neurones and transported to the nerve terminals probably by both slow and rapid axoplasmic flows. ChAT exists in at least two forms in cholinergic nerve terminals: (i) soluble; and (ii) non-ionically membrane-bound forms...
November 1999: Pathology International
T Sobreviela, D O Clary, L F Reichardt, M M Brandabur, J H Kordower, E J Mufson
The present investigation used an antibody directed against the extracellular domain of the signal transducing nerve growth factor receptor, trkA, to reveal immunoreactive perikarya or fibers within the olfactory bulb and tubercle, cingulate cortex, nucleus accumbens, striatum, endopiriform nucleus, septal/diagonal band complex, nucleus basalis, hippocampal complex, thalamic paraventricular and reuniens nuclei, periventricular hypothalamus, interpeduncular nucleus, mesencephalic nucleus of the fifth nerve, dorsal nucleus of the lateral lemniscus, prepositus hypoglossal nucleus, ventral cochlear nucleus, ventral lateral tegmentum, medial vestibular nucleus, spinal trigeminal nucleus oralis, nucleus of the solitary tract, raphe nuclei, and spinal cord...
December 22, 1994: Journal of Comparative Neurology
C M Yates, J Simpson, A Gordon, J E Christie
Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in anterior and posterior grey matter of the lumbar spinal cord and in temporal and frontal cortex from six cases of Alzheimer-type dementia (ATD), one case of Down's syndrome, three cases of schizophrenia (SZ) and six controls. Compared with control and SZ values, ChAT and AChE were reduced in ATD cerebral cortex. ChAT was reduced, and AChE unaltered, in ATD spinal cord. Decreased cord ChAT may be related to electrophysiological abnormalities which have been reported in motor nerves of patients with Alzheimer's disease...
1989: Journal of Neural Transmission. Parkinson's Disease and Dementia Section
B Knüsel, L E Burton, F M Longo, W C Mobley, V E Koliatsos, D L Price, F Hefti
NGF is a neurotrophic factor for basal forebrain cholinergic neurons and may serve to counteract the cholinergic deficits that are observed in Alzheimer's disease. Prior to the introduction of clinical trials, it is essential that recombinant human NGF (rhNGF) be produced and that its actions on target cells in the CNS be demonstrated. We prepared rhNGF and examined its actions on fetal rat brain neurons in culture including, in particular, the cholinergic neurons of the basal forebrain. rhNGF was more potent in increasing choline acetyltransferase (ChAT) activity in septal cultures than NGF purified from mouse salivary glands (mNGF)...
December 1990: Experimental Neurology
Y Tajima, F Moriwaka, K Tashiro
We have established a new in situ hybridization method utilizing non-radiolabeled probes. Using this technique, we have attempted to detect the choline-acetyltransferase (ChAT) gene expression in rat spinal cord. It was revealed that the ChAT gene was expressed mainly in the cytoplasm of motor neurons and para-central cells. On the other hand, ChAT protein has already been reported to exhibit a diffused distribution in the cholinergic fibers. Comparing the localization of the ChAT gene with that of the ChAT protein, the ChAT gene was shown to exist only in the cytoplasm surrounding the nuclei...
May 1991: Nō to Shinkei, Brain and Nerve
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