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Methamphetamine exposure during brain development alters the brain acetylcholine system in adolescent mice
Jessica A Siegel1, Byung S Park, Jacob Raber
1Department of Behavioral Neuroscience, ONPRC, Oregon Health and Science University, Portland, Oregon 97239, USA.
Insights
Maternal methamphetamine use during pregnancy can cause long-term cognitive deficits in children. This study reveals methamphetamine exposure alters the acetylcholine system in adolescent mice, particularly in females, impacting brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Maternal methamphetamine use leads to cognitive impairments in offspring.
- The acetylcholine system is crucial for cognitive functions.
- Mechanisms behind methamphetamine-induced cognitive deficits remain unclear.
Purpose of the Study:
- Investigate long-term effects of prenatal methamphetamine exposure on the acetylcholine system.
- Examine alterations in adolescent and adult mice.
- Determine sex differences in methamphetamine's impact.
Main Methods:
- Assessed acetylcholine neuron density in basal forebrain.
- Quantified acetylcholine axon area in the hippocampus.
- Measured muscarinic acetylcholine receptor levels.
- Utilized adolescent (postnatal day 30) and adult (postnatal day 90) mice.
Main Results:
- Methamphetamine exposure increased acetylcholine neuron density and axonal area in adolescent females.
- No changes observed in GABA cells or total neurons in the basal forebrain.
- Increased muscarinic acetylcholine receptors in the hippocampus of both adolescent males and females.
- Sex-dependent effects observed, with females showing more profound changes.
Conclusions:
- Prenatal methamphetamine exposure alters the acetylcholine system during adolescent development.
- These alterations are linked to potential long-term cognitive impairments.
- Females exhibit greater sensitivity to methamphetamine's effects on the developing acetylcholine system.
Abstract:
Children exposed to methamphetamine during brain development as a result of maternal drug use have long-term hippocampus-dependent cognitive impairments, but the mechanisms underlying these impairments are not understood. The acetylcholine system plays an important role in cognitive function and potential methamphetamine-induced acetylcholine alterations may be related to methamphetamine-induced cognitive impairments. In this study, we investigated the potential long-term effects of methamphetamine exposure during hippocampal development on the acetylcholine system in adolescence mice on postnatal day 30 and in adult mice on postnatal day 90. Methamphetamine exposure increased the density of acetylcholine neurons in regions of the basal forebrain and the area occupied by acetylcholine axons in the hippocampus in adolescent female mice. In contrast, methamphetamine exposure did not affect the density of GABA cells or total neurons in the basal forebrain. Methamphetamine exposure also increased the number of muscarinic acetylcholine receptors in the hippocampus of adolescent male and female mice. Our results demonstrate for the first time that methamphetamine exposure during hippocampal development affects the acetylcholine system in adolescent mice and that these changes are more profound in females than males.
