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Neonatal 5,7-DHT lesions cause sex-specific changes in mouse cortical morphogenesis
C F Hohmann1, C Richardson, E Pitts
1Department of Biology, Morgan State University, Cold Spring Lane and Hillen Rd., Baltimore, MD 21251, USA. chohmann@morgan.edu
Neural Plasticity
|August 7, 2001
Summary
Neonatal serotonin and norepinephrine depletion in mice altered cortical development, increasing layer width. These findings suggest monoaminergic and cholinergic pathways have opposing roles in brain development and may explain sex differences in developmental disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Neuroanatomy
Background:
- Cholinergic and monoaminergic projections influence neocortical development and plasticity.
- Previous studies showed cholinergic nucleus basalis magnocellularis (nBM) lesions decrease cortical layer width and impair cognition.
- Electrolytic lesions may affect adjacent monoaminergic fibers, confounding results.
Purpose of the Study:
- To investigate the impact of selective neonatal monoaminergic depletion using 5,7-dihydroxytryptamine (5,7-DHT) on cortical laminar morphology.
- To explore potential opposing roles of monoaminergic and cholinergic systems in cortical development.
- To provide an anatomical basis for previously observed behavioral alterations and understand sex-specific effects.
Main Methods:
- Neonatal focal 5,7-DHT injections into the nBM region of mice.
- Assessment of cortical serotonin and norepinephrine levels.
- Quantitative analysis of cortical layer widths in adult mice (male and female).
Main Results:
- Neonatal 5,7-DHT lesions caused significant, age-attenuating cortical depletion of serotonin and norepinephrine.
- Generally, cortical layer widths increased post-lesion, with region, layer, and sex-specific variations.
- Findings correlate with previous reports of long-term behavioral alterations following similar lesions.
Conclusions:
- Neonatal monoaminergic projections may have opposing effects to cholinergic projections on developing cortical structure.
- Observed morphological changes provide an anatomical substrate for behavioral deficits.
- Data suggest implications for understanding developmental disorders and sex differences in their prevalence.