Prenatal Hypoxia Predisposes to Impaired Expression of the chrna4 and chrna7 Genes in Adult Rats without Affecting Acetylcholine Metabolism during Embryonic Development.

Abstract

Previous studies have shown that the combined effect of fetal hypoxia and maternal stress hormones predetermines tendency to nicotine addiction in adulthood. This study in rats aimed to investigate the effect of prenatal severe hypoxia (PSH) on acetylcholine metabolism in the developing brain, as well as on expression of acetylcholine receptors chrna4 and chrna7 in both the developing brain and adult brain structures following nicotine consumption. In the developing brain of PSH rats, no changes were found in the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) or disturbances in the acetylcholine levels. However, decreased chrna4 expression was detected on the day 15 of pregnancy, while elevation in the chrna7 expression was observed on the days 15 and 16 of embryogenesis. In adulthood, the consequences of PSH were manifested as decreased expression of chrna4 in the medial prefrontal cortex (PFC), nucleus accumbens (NAacc), and hypothalamus (HT), decreased expression of chrna7 in the PFC and hippocampus (HPC). Whereas, nicotine consumption did not decrease the expression levels of chrna4 and chrna7 compared to the control group in the adult PSH rats. Thus, prenatal hypoxia predisposes to impaired expression of the chrna4 and chrna7 genes in adult rats without affecting acetylcholine metabolism during embryonic development.