Effect of chronic maternal L-Glu intake during gestation and/or lactation on oxidative stress markers, AMPA Glu1 receptor and adenosine A1 signalling pathway from foetal and neonatal cerebellum

Purinergic Signal. 2024 Apr;20(2):181-192. doi: 10.1007/s11302-023-09959-6. Epub 2023 Jul 17.

Abstract

L-Glutamate (L-Glu) is an amino acid present in the diet that plays a fundamental role in the central nervous system, as the main excitatory neurotransmitter participating in learning and memory processes. In addition, the nucleoside adenosine has a crucial role in L-Glu metabolism, by regulating the liberation of this neurotransmitter through four different receptors: A1, A2A, A2B and A3, which activate (A2A and A2B) or inhibit (A1 and A3) adenylate cyclase pathway. L-Glu at high concentrations can act as a neurotoxin and induce oxidative stress. The study of the oxidative stress correlated with an excess of L-Glu consumption during maternity is key to understand its effects on foetuses and neonates. Previous studies have shown that there is a change in the receptor levels in the brain of pregnant rats and their foetuses when mothers are administered L-Glu during gestation; however, its effect on the cerebellum is unknown. Cerebellum is known to be responsible for motor, cognitive and emotional functions, so its possible involvement after L-Glu consumption is an important issue to study. Therefore, the aim of the present work was to study the effect of L-Glu exposure during gestation and lactation on oxidative stress biomarkers and neurotransmitter receptors from the cerebellum of foetuses and neonates. After maternal L-Glu intake during gestation, oxidative stress was increased, as the ionotropic L-Glu receptors, and GluR1 AMPA subunit levels were altered in foetuses. A1 adenosine receptor suffered changes after L-Glu treatment during gestation, lactation or both, in lactating neonate cerebellum, while adenylate cyclase activity remain unaltered. Further studies will be necessary to elucidate the importance of L-Glu intake and its possible excitotoxicity in the cerebellum of Wistar rats during the pregnancy period and their involvement in long-term neurodegeneration.

Keywords: Adenosine A1 receptor; Gestation; Glutamate; Lactation; Oxidative stress.

MeSH terms

  • Adenosine / metabolism
  • Adenylyl Cyclases / metabolism
  • Adenylyl Cyclases / pharmacology
  • Animals
  • Cerebellum / metabolism
  • Female
  • Fetus / metabolism
  • Glutamic Acid* / metabolism
  • Humans
  • Lactation
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Agents / pharmacology
  • Oxidative Stress
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Wistar
  • Receptors, AMPA
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Glutamic Acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Adenosine
  • Receptors, AMPA
  • Adenylyl Cyclases
  • Neurotransmitter Agents