Long-term effects of basal forebrain lesions on cholinergic, noradrenergic and serotonergic markers in mouse neocortex.
Lesions of basal forebrain cholinergic neurons projecting to cerebral cortex and hippocampus have recently been exploited as animal models for some of the neurochemical and behavioral deficits of Alzheimer's disease. We have observed that electrolytic lesions of cholinergic basal forebrain nuclei can lead to morphological plasticity in adult mouse cortex. In the present study, the acute and chronic sequelae of basal forebrain electrolytic lesion on cortical synaptic chemistry have been examined. In addition to choline acetyltransferase (ChAT) activity, levels of norepinephrine and of serotonin were reduced within a week after the lesion. Recovery of ChAT activity and of serotonin levels began within a month after the lesion. Serotonin type 2 receptor binding exhibited an acute reduction after the lesion in ipsilateral cortex, followed later by a chronic bilateral decrease. No significant changes in beta-adrenergic receptors were apparent at any time after the lesion despite a permanent and bilateral reduction of norepinephrine levels after the lesion. The potential significance of these results for cortical plasticity regulation and Alzheimer's disease is discussed.
Höhmann
C F
CF
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Coyle
J T
JT
D000818:Animals; D001921:Brain / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D007839:Functional Laterality; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
D011985:Receptors, Serotonin; D012701:Serotonin; D002795:Choline O-Acetyltransferase; D009638:Norepinephrine