Effects of methamphetamine in the hippocampus of cynomolgus monkeys according to age

Abstract

The aim of this study was to investigate differentially expressed genes (DEGs) and their functions in the hippocampi after methamphetamine (MA) administration in cynomolgus macaques according to age. Cynomolgus monkeys were divided by age as follows: control, 6–12 months (age 1, A1), 3–4 (A2) years, 7–9 (A3) years, and more than 11 years (A4). After MA was injected into the monkeys (2 mg/kg, intramuscular injection in each of A1, A2, A3 and A4), we performed large-scale transcriptome profiling in the hippocampus. Some genes associated with neuron differentiation, development, and transmission were validated with real-time RT-PCR. The expression patterns of validated genes were also investigated in the hippocampi of monkeys one year after a single injection of MA. The correlation of DEGs between A2 and A3 animals, who are similar to humans in early teens to early twenties, was higher than that of other groups, showing the possibility that biological mechanisms in the hippocampus of A2 and A3 are similarly affected by MA. Genes associated with neuron differentiation (FEZF1, GPR1N1, DLX1, and KCNIP2), neuron (projection) development (NGFR, CDKN1C, and VAX2), and synaptic transmission (SYT4, SYT1, GAD2, CORT, and NPTX2) were differentially expressed among control and MA-treated animals. In particular, the expression patterns of GPR1N1 among control and MA-treated animals following a single injection of MA were not altered even one year after single MA administration. Our results suggest that genes associated with neuron differentiation and synaptic transmission in the hippocampus of different maturation stages are differentially regulated by MA.