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Chronic nicotine treatment prevents neuronal loss in neocortex resulting from nucleus basalis lesions in young adult and aged rats

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Molecular and Chemical Neuropathology

Abstract

In both young adult and aged rats, we tested the ability of chronically administered nicotine to rescue neocortical neurons from transneuronal degeneration resulting 5 mo after ibotenic acid (IBO) lesioning of the nucleus basalis magnocellularis (NBM). Young adult (2–3 mo-old) and aged (20–22-mo-old) rats were given unilateral infusions of IBO (5 μg/1 μL) at two sites within the NBM. Following surgery, animals began receiving either daily ip injections of nicotine (0.2 mg/kg) or saline vehicle. Treatment continued for 5 mo, at which time all animals were sacrificed and their brains processed histologically. For each brain, computer-assisted image analysis was then used to analyze the unlesioned (left) and lesioned (right) side of five nonconsecutive brain sections from parietal cortex Layers II–IV and V. NBM lesioning in both young adult and aged vehicle-treated rats resulted in a significant 16–21% neuronal loss ipsilateral to NBM lesioning in neocortical Layers II–IV. Aged NBM-lesioned rats also exhibited a significant 12% neuronal loss in neocortical Layer V ipsilaterally. By contrast, those NBM-lesioned young adult and aged rats that received daily nicotine treatment postsurgery did not show any ipsilateral neuronal loss in the same parietal cortex areas, indicating that chronic nicotine treatment prevented the transneuronal degeneration of neocortical neurons resulting 5 mo afer NBM lesioning. Nicotine treatment alone did not have any effect on neuronal density, neuronal size, or glial cell numbers in the neocortex. The neuroprotective/neurotrophic action of nicotine in the neocortex following NBM lesions may involve activation of pre- and/or postsynaptic nicotinic receptors to maintain depolarizing influences or neurotrophin synthesis, or it may involve nicotine’s ability to increase glucose utilization and cerebral blood flow.

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Socci, D.J., Arendash, G.W. Chronic nicotine treatment prevents neuronal loss in neocortex resulting from nucleus basalis lesions in young adult and aged rats. Molecular and Chemical Neuropathology 27, 285–305 (1996). https://doi.org/10.1007/BF02815110

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