Muscarinic and nicotinic cholinergic binding sites in alzheimer's disease cerebral cortex

Kellar, Kenneth J.; Whitehouse, Peter J.; Martino-Barrows, Andrea M.; Marcus, Kendall A.; Price, Donald L.

doi:10.1016/0006-8993(87)91556-3

Cited by 142 publications

(72 citation statements)

References 28 publications

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“…Cholinergic mechanisms have long been demonstrated to be crucial for learning and memory, however the majority of research efforts over past decades has been devoted to investigation of signaling through the muscarinic subtype cholinergic receptors (see Bartus 2000 for review). Recent attention has been focused on the involvement of nAChRs in mnemonic functions in part because of observations that nicotinic receptor binding is reduced in the cortex and hippocampus of Alzheimer's Disease (AD) patients (Kellar et al 1987;Nordberg et al 1988;Nordberg and Winblad 1986) and in the striatum of Parkinson's Disease (PD) patients (Aubert et al 1992;Court et al 2000b;Perry et al 1998). Consistent with the finding for postmortem AD brain tissue, transdermal administration of nicotine can improve learning rates and attentional processing in AD patients (Min et al 2001;White and Levin 1999;Wilson et al 1995).…”

Section: Introductionmentioning

confidence: 83%

Effects of nicotine and mecamylamine on cognition in rhesus monkeys

et al. 2004

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Rationale-Nicotine and other agonists of nicotinic cholinergic receptors (nAChR) have been shown to improve performance in specific memory domains in rodents and monkeys. Such beneficial effects are observed in preclinical models of age-related cognitive decline, stimulating interest in nAChR ligands as possible therapeutics. Prior work has typically focused on assays of spatial working memory in rodent studies and visual recognition memory in monkey studies.Objective-The current study was conducted to determine the role nAChRs play in multiple types of memory in monkeys.Methods-Rhesus monkeys (N = 6) were trained to perform a battery of 6 behavioral tasks and then serially challenged with acute doses of nicotine (3.2-56 μg/kg, i.m.) and the nAChR antagonist mecamylamine (0.32-1.78 mg/kg, i.m).Results-Nicotine improved performance on tests designed to assay visual recognition memory, spatial working memory and visuo-spatial associative memory while mecamylamine impaired visuospatial associative memory. Ballistic and fine motor performance was not significantly improved by nicotine but fine motor performance was impaired by mecamylamine.Conclusions-Although nicotine may improve performance in multiple domains, effects on visuo-spatial associative memory is the most specifically attributable to nAChR signaling.

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Section: Introductionmentioning

confidence: 83%

Effects of nicotine and mecamylamine on cognition in rhesus monkeys

et al. 2004

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“…Many investigators have reported a marked reduction in the activity of choline acetyltransferase (ChAT), an enzyme involved in the synthesis of Ach, in the cerebral cortex, striatum and hippocampus of the brains of DAT patients [2]. Recently, the decrease in nicotinic acetylcholine receptors (n-Ach-R) in the cerebral cortex of DAT brains has also been reported [6,7,8].…”

Section: Disturbancementioning

confidence: 99%

Evaluation of Estrogen Treatment in Female Patients with Dementia of the Alzheimer Type.

et al. 1994

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Abstract. This study was designed to investigate the therapeutic efficacy of estrogen in female patients with dementia of the Alzheimer type (DAT). Fifteen DAT patients with a mean age of (x ± SE) 71.9 ± 2.4 years were treated with 0.625 mg of conjugated equine estrogens orally twice a day for 6 weeks. Of the 15 DAT patients, 4 were diagnosed as mild, 7 as moderate and 4 as severe. The effects of estrogen on DAT patients were evaluated by psychometric assessments, behavior rating scales, regional cerebral blood flow (rCBF) measurement and quantitative EEG analysis. Psychometric assessments consisted of Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale (HDS). Dementia syndromes were evaluated by the CBS-Scale (GBSS) and Hamilton Depression Rating Scale (HDRS). During estrogen replacement therapy (ERT), the mean MMSE score (x ± SE) increased significantly from 11.6 ± 1.9 to 13.2 ± 2.0 at 3 weeks (P<0.01) and 13.8 ± 2.0 at 6 weeks (P<0.001). The mean HDS score increased significantly from 8.6 ± 2.1 to 11.5 ± 2.3 at 3 weeks (P<0.001) and 11.6 ± 2.6 at 6 weeks (P<0.01). Significant improvements in the mean scores of the GBSS and HDRS were also observed in the estrogentreated group, but not in the untreated control group with a mean age of 71.2 ± 2.5 years (n=15). The rCBF was measured by single photon emission computed tomography (SPELT). ERT increased the mean rCBF significantly in the lower frontal region (P<0.01) and primary motor area (P<0.02) of the right hemisphere. The mean absolute power delta band values in both left and right frontal EEG (Fp, and Fp2) (P<0.01) and theta1 band values in Fp2 (P<0.05) decreased significantly during ERT. It is inferred that ERT significantly improves cognitive functions, dementia symptoms, regional cerebral blood flow and EEG activity in female patients with DAT.

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“…For example, the high affi nity nicotine receptors are among the fi rst (if not the fi rst) neurotransmitter system whose expression is diminished in Alzheimer ' s disease. 1 Subsequent studies [2][3][4] have suggested that chronic nicotine administration might in fact play a benefi cial role in slowing the progression of this disease. While this fi nding is controversial, there is now ample evidence supporting a therapeutic benefi t from nicotine in Parkinson ' s 5 disease, and as a neuroprotectant to toxic insults such as excitotoxins [6][7][8][9][10] or Beta-amyloid derived peptides.…”

Section: Introductionmentioning

confidence: 99%