Nicotinic receptors in human brain: topography and pathology

Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380

“…In the cerebellum, 5-[ 125 I]-A-85380 binding appears more concentrated in the molecular layer than the granular layer, confirming previously reported [ 3 H]cytisine (Aubert et al, 1992a) and [ 3 H]epibatidine distribution (Court et al, 2000a); however, [ 3 H]nicotine binding shows higher binding in the granular than the molecular layer (Court and Perry, 1995a). Moderate 5-[ 125 I]-A-85380 binding was also present in the dentate nucleus.…”

“…Deficits in striatal nAChRs do not appear, at least in some patients, to be associated with nigrostriatal dopaminergic deficits (Piggott et al, 1999) and are therefore more likely to be related to reduced striatal afferents from other sources, such as cortical areas subject to atrophy in AD and possibly thalamic areas. It may be that these striatal nAChRs deficits are responsible for disorders of movement observed in late stages of AD (Court et al, 2000a). Significantly reduced 5-[ 125 I]-A-85380 binding in AD compared to controls was also found in the entorhinal cortex, consistent with reports of deficits in [ 3 H]nicotine binding (Court et al, 2001) and [ 3 H]epibatidine binding and a4 subunit protein expression in the neocortex in AD (Martin-Ruiz et al, 1999;Guan et al, 2000).…”

“…[ 125 I]-a-conotoxin MII binding in mouse brain has also been shown to be high in the superficial layers of the superior colliculus, nigrostriatal pathways, optic tract, olivary pretectal, mediolateral and dorsolateral geniculate nuclei (Whiteaker et al, 2000) and therefore 5-[ 125 I]-A-85380 in these areas could also reflect both a4b2 and a6b2 subtype distributions. 5-[ 125 I]-A-85380 binding in the GP is largely absent, which is consistent with low [ 3 H]nicotine binding in human brain tissue (Court et al, 2000a).…”

“…Reductions in nAChR density have been identified in a number of neurodegenerative disorders including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease (PD) (Rinne et al, 1991;Perry et al, 1995;Court et al, 2000a). In AD, binding assays with [ 3 H]ABT-418 and [ 3 H]epibatidine (Warpman and Nordberg, 1995) and immunochemical analysis (Martin-Ruiz et al, 1999;Wevers et al, 1999;Guan et al, 2000;Burghaus et al, 2000) indicate that the major contributor to loss of nAChRs in cortical areas is the a4 subunit.…”

Regulatory mechanisms that govern nicotinic synapse formation in neurons

“…In the CNS, their functions also include modulating neurotransmitter release from presynaptic terminals, reinforcing nicotine addiction, and increasing attention, arousal and memory formation (Dani and Heinemann, 1996;Jones et al, 1999;Perry et al, 1999). Abnormalities in nAChR number and function have been implicated in neurologic disorders such as Alzheimer's disease, Parkinson's disease, familial frontal lobe epilepsy, and auditory-gating schizophrenia (Lena and Changeux, 1997;Court et al, 2000).…”