Neonatal 5,7-DHT Lesions Cause Sex-Specific Changes in Mouse Cortical Morphogenesis

[摘要] Both monoaminergic and cholinergic afferentprojections to the neocortex putatively modulatecortical morphogenesis and plasticity. Previouslywe showed that neonatal,electrolytic lesions:the cholinergic nucleus basalis magnocel!ularis(nBM) projections to the neocortex result insignificant decreases-of cortical layer width thatcorrelate with cognitive alterations. Such electrolyticlesions, performed for lack of a selectiveneurotoxin in mice, may affect mono- aminergicfibers of passage. Here, we investigate the effectsof neonatal 5,7 dihydroxytryptamine (5,7-DHT)focal injections into the nBM region on corticallaminar morphology in adult male and femalemice. 5,7-DHT lesions on the first postnatal dayresulted in significant cortical depletion of bothserotonin and norepinephrine that attenuatedwith age. Generally, cortical layer widthsincreased in response to the lesion; the effectswere layer, region, and sex specific. Previousreports from our laboratories described longtermbehavioral alterations after comparablefocal, neonatal 5,7-DHT lesions. The studiesdescribed here provide an anatomical basis forsuch behavioral alterations. Our data suggestthat monoaminergic and cholinergic projections to the cortex may have opposite effects on thedeveloping cortical neuropil. Jointly, ourmorphological and behavioral findings mayhave important implications for a variety ofdevelopmental disorders in humans andprovide some insights into sex differences in thepenetrance of these disorders.

[学科分类] 精神健康和精神病学