Hypoxia is one of the most dangerous impacts during prenatal development because the continuous supply of oxygen is inevitable for proper tissue development during the fetal period. Especially the central nervous system is highly vulnerable to limited oxygen during development and hypoxia can, therefore, lead to morphological and structural changes in the brain and subsequent behavioral changes later in life. Glutamate and acetylcholine are the most important neurotransmitter systems for the development and cognitive processes. Our study aimed to assess the impact of prenatal hypoxia on the postnatal development of the rat offspring and on the cholinergic and glutaminergic neurotransmitter systems in their brain. Pregnant Wistar rats were subjected to hypoxia (10,5% O2) for 12 hours on gestational day 20. Postnatal sensorimotor development of their offspring was assessed by righting reflex, air-righting, and startle reflex test. Prefrontal cortex (PFC) and hippocampus of their male offspring (nHYP = 6, nCON = 11) were collected on postnatal day 34. Relative expression of Slc18a3 and Chat, as markers of cholinergic transmission, and Grin1 encoding a subunit of glutaminergic NMDA receptor were evaluated. Actb and B2m were used as reference genes. Sensorimotor development of hypoxic pups was slower compared to control group, seen as significant delay in righting reflex (p<0.01), and lower percentage of accomplishment at air-righting (p<0.05) and startle reflex test (p<0.05). RT-qPCR showed a decrease in relative expression of Slc18a3 (p<0.05) and Chat (p<0.01) in PFC of the hypoxic group compared to the control group, suggesting a negative effect of prenatal hypoxia on acetylcholine synthesis and vesicular transport. On the other side, hypoxia caused an increase of Grin1 (p<0.01) and Chat (p<0.05) expression in the hippocampus. We propose that this elevation may be caused by some reparational mechanisms induced by hypoxia, e.g. neurotrophic factors, as the hippocampus is one of the few regions in that neurogenesis continues up to adulthood. In conclusion, hypoxia caused a significant delay in postnatal development of rat pups and changes in neurotransmitter systems in both PFC and hippocampus. However, the extent of hypoxia-induced injury differed in these regions, probably due to the enhanced capacity of hippocampal reparational mechanisms.
This study was supported by the grant VEGA 2/0154/20 and SAS Programme for PhD students’ grant APP0054.