Autoradiographic distribution of [3H]nicotine binding in human cortex: Relative abundance in subicular complex
ABSTRACT Distinct patterns of [3H]nicotine (3 nm) binding were apparent in various regions of adult human neo- and archicortex. Receptor binding was greatest in the subicular complex—particularly presubiculum—and entorhinal cortex, where it was prominent in the characteristic parvo- and magnocellular islands of these regions and in middle layers of entorhinal cortex. In somatosensory cortex (Brodmann areas 3, 1 and 2) and occipital (area 17) cortex binding was highest in the upper and lower layers, and relatively sparse in the sensory input, layer IV. In primary motor (area 4) and temporal (area 21) cortex, binding in the outer half of the cortical ribbon was denser than that in the inner half and a distinct band was apparent in temporal and cingulate (area 32) in the lower portion of layer III. In prefrontal association cortex the pattern of binding was less distinct although slightly higher in the lower architectonic layers. There was generally little binding in the hippocampus (areas CA1–4) and dentate gyrus with the exception of the stratum lacunosum moleculare in CA2–3 and, to a lesser extent, supra- and subgranule zones of the dentate. These patterns of reactivity, which are distinct from that of the major cortical cholinergic innervation, suggest that the nicotinic receptor, detected using nanomolar concentrations of [3H]nicotine, may primarily be associated with intracortical circuitry in the neocortex. The relatively high density in entorhinal and subicular regions may be related to the extensive phylogenetic development of these regions which has occurred in conjunction with the development of multimodal association circuitry in the human cortex.
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ABSTRACT: The vulnerability of the human hippocampal complex to disease, trauma, and aging indicates the necessity to target this area therapeutically. The distribution and density of transmitter receptors provide a rational basis for this approach, and in this study the topography of 11 different pharmacological sites is compared with the cholinergic innervation, which is particularly vulnerable in dementia. The regional distribution of cholinergic innervation to the normal adult human hippocampus and adjacent cortex, marked by acetylcholinesterase (AChE) fiber and terminal reactivity, is notable for its concentration in CA2/3 of Ammon's horn and the dentate fascia. Neither nicotinic (high-affinity nicotine binding) nor muscarinic ("M1" or "M2") cholinergic receptor binding paralleled this distribution. In Ammon's horn, 5-HT2 and kainate receptor binding more closely resembled the pattern of AChE, being concentrated in CA2-4 compared with CA1. By contrast, muscarinic M1 and M2, 5-HT1A, benzodiazepine (including zolpidem-insensitive binding), NMDA (MK801), and AMPA/QUIS receptors were higher in CA1 and/or subiculum. Kainate binding, like AChE, was high in CA4. 5-HT2 and nicotinic binding partially mimicked the pattern of AChE around the granule layer. In the subicular complex and parahippocampal gyrus, where cholinergic activity is relatively lower, muscarinic, 5-HT1A, and benzodiazepine binding were relatively high and the nicotinic receptor was remarkable for its highest density compared to other areas examined. In stratum lacunosum-moleculare of CA1, which was relatively low in AChE activity, there was a dense band of nicotinic, M2, and benzodiazepine receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)Hippocampus 07/1993; 3(3):307-15. DOI:10.1002/hipo.450030306 · 4.30 Impact Factor
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ABSTRACT: Neuronal nicotinic acetylcholine receptors (nAchRs) are multimeric proteins constituted of two different subunits, alpha and beta, with different subtypes arrangement and different pharmacological and functional properties. nAchRs mediate neurotransmission in many central and peripheral synapses and appear to be affected in human degenerative disorders. We have studied the distribution of nAchR in human brain, particularly in the hippocampus and thalamus, by binding of 3H-nicotine and 3H-cytisine and by in situ hybridization with human alpha 3 and beta 2 nAchR subunits of mRNA. An alpha 3 probe shows a strong hybridization signal in the thalamus, while a beta 2 probe has a good signal at the level of the enthorinal cortex, hippocampus and in caudate and putamen. The alpha 3 and beta 2 mRNA localization is different from that described in other species. 3H-nicotine and 3H-cytisine binding were very similar in terms of anatomical distribution and comparable to the binding described in other animal species. The binding of the two ligands was distributed over the areas labeled by the alpha 3 and beta 2 probes and did not completely overlap with either of the subunits.Neurochemistry International 08/1994; 25(1):69-71. DOI:10.1016/0197-0186(94)90055-8 · 2.65 Impact Factor
Article: CNS Nicotinic Receptors[Show abstract] [Hide abstract]
ABSTRACT: CNS nicotinic acetylcholine receptors are a family of ligand-gated cation channels that allow the passage of calcium ions. They are structurally and functionally distinct from nicotinic receptors at the neuromuscular junction. CNS nicotinic receptors show a variation in distribution and pharmacology. The number of these receptors is reduced with normal aging, and a further reduction in number occurs in dementing conditions that are common in elderly individuals. A comparison of receptor loss in the substantia nigra of patients with Parkinson’s disease and Lewy body dementia indicates that this process may occur early in the disease and precede cell loss. In addition, nicotine binding sites in humans are concentrated in the entorhinal cortex and subicular formation, areas that are affected early in the course of Alzheimer-type disease. The number of nicotine binding sites is high in human neonatal brain, at which stage exposure to nicotine and tobacco smoke is deleterious. Conversely, epidemio-logical evidence suggests that later in life tobacco smoking may offer some protection against Parkinson’s and Alzheimer’s diseases. Exposure to nicotinic agonists and tobacco smoke increases the number of brain nicotinic receptors both in humans and experimental animals, although the functional significance of this and its precise relationship to receptor desensitisation is not completely understood. Acute exposure to nicotine and nicotinic antagonists has beneficial and adverse effects, respectively, on cognitive function. Subcutaneous administration of nicotine to patients with Alzheimer’s disease improves discriminative sensitivity and reaction times. Available nicotinic agonists appear to induce diverse functional responses, and models for the testing of such novel compounds are needed.CNS Drugs 09/1994; 2(3). DOI:10.2165/00023210-199402030-00006 · 4.38 Impact Factor