GABA function may be related to the impairment of learning and memory caused by systemic prenatal hypoxia-ischemia

Neurobiol Learn Mem. 2018 Mar;149:20-27. doi: 10.1016/j.nlm.2018.01.004. Epub 2018 Feb 3.

Abstract

Intrauterine adverse conditions may be responsible for long-lasting damages which impact health even during adult phase. Hypoxic-ischemic (HI) events are a relevant cause of newborn mortality and the principal factor leading to permanent brain lesions. Using a model in which the ovarian and uterine flux of a pregnant rat is obstructed for 45 min we have described oligodendrocyte death, astrogliosis and neuronal loss. In this work we investigated hippocampal neuronal population and performed a functional evaluation of memory and learning of young rats that had been affected by prenatal HI. Anesthetized Wistar rats on the 18th gestation day had the uterine horns exposed and the ovarian and uterine arteries clamped for 45 min (HI group). Sham-operated rats (SH group) had the horns exposed but no arteries were clamped. We measured the levels of different proteins related to excitatory/inhibitory transmission in the hippocampi of young pups (P45). Histological evaluation was also performed in order to characterize hippocampal neuronal population. Rats from both groups were tested through Novel Object Recognition Test (NORT) using two inter-trial intervals: 5 min and 8 h. Here we show a loss in the total number of hippocampal neurons although the immunostaining of parvalbumin and levels of GAD enzyme were increased in HI group. Functional assessment indicated a marked difference concerning HI learning and memory abilities. Our results reflect permanent damages concerning GABA function which may disturb neurotransmitter homeostasis leading to the observed deficits in learning and memory.

Keywords: Development; GAD; Hippocampus; NORT; Prenatal insult; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Hippocampus / metabolism*
  • Hypoxia-Ischemia, Brain / complications
  • Hypoxia-Ischemia, Brain / metabolism*
  • Learning / physiology*
  • Maze Learning
  • Memory / physiology*
  • Memory Disorders / complications
  • Memory Disorders / metabolism*
  • Neurons / metabolism
  • Parvalbumins / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Rats
  • Rats, Wistar
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Parvalbumins
  • gamma-Aminobutyric Acid