Neuronal growth and synaptogenesis are inhibited by prenatal methamphetamine exposure leading to memory impairment in adolescent and adult mice

Synaptogenesis plays critical roles in learning and memory processes and is susceptible to substance abuse toxicity. The present study aimed to elucidate the long-lasting effects of prenatal methamphetamine exposure on synaptogenesis and learning and memory. The involvement of BDNF-TrkB signaling was also investigated. Pregnant mice (C57BL/6 JNc) were administered methamphetamine (5 mg/kg, s.c.) on gestation days 8-15. Primary hippocampal cultures were prepared from fetuses at gestational day 16.5 to study neuronal morphology and synaptogenesis. The expression of synaptic proteins, BDNF and TrkB receptor was determined in postnatal day 14 (PND14), adolescent and adult mice; memory tests were also conducted. MA exposure decreased axon length and diameter, and synaptic areas in the primary cultures. Presynaptic protein was decreased in the hippocampus of PND14 mice prenatally exposed to MA, while increases in postsynaptic protein (PSD-95) were found in MA-exposed adolescent and adult mice. BDNF expression was enhanced in the prefrontal cortex and striatum of MA-exposed PND14 mice. Memory impairment was observed in MA-exposed adolescent and adult mice compared to control mice. Prenatal MA exposure disrupted neuronal growth and synapse formation in the developing brain with only short-term interference of the BDNF-TrkB signaling pathway, resulting in the adaptation of postsynaptic neurons. Alterations in the developing brain and synaptogenesis lead to long-lasting learning and memory impairment. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

Prenatal exposure to methamphetamine disrupts synaptogenesis and impairs learning and memory, with alterations in the BDNF-TrkB signaling pathway. This disruption leads to long-lasting memory impairment in adolescent and adult mice.