Chronic inhibition of brain phospholipase A2 in adult rats impairs the survival of newborn mature neurons in the hippocampus.

Abstract

Adult neurogenesis occurs in the hippocampal dentate gyrus (DG) and lateral ventricles, and includes cell proliferation and neuronal differentiation, maturation and survival. In vitro studies suggest a role for phospholipase A2 (PLA2) in neuronal differentiation/maturation and survival. This study aimed to investigate the effect of in vivo chronic inhibition of brain PLA2 in adult rats on the number of newborn mature neurons in the DG. Male Wistar rats were injected with BrdU (cell proliferation marker) and 2weeks later (beginning of neuronal maturation) sham-operated or infused intracerebroventricularly with either vehicle (DMSO in saline) or PLA2 inhibitor (MAFP dissolved in the vehicle) for 14days via osmotic minipump. The animals were euthanised 28days post-BrdU and their brains immunostained for BrdU and BrdU plus NeuN (mature neuronal marker) for analysis of surviving cells. MAFP reduced the number of BrdU(+) cells in the ventral DG (p<0.05 vs. sham; p<0.01 vs. DMSO) and the number of BrdU(+)NeuN(+) cells in the ventral (p<0.01 vs. sham and DMSO) and whole DG (p<0.02 vs. sham and DMSO). There was no effect of MAFP in the dorsal DG. These findings show that chronic PLA2 inhibition in adult rat hippocampus decreases the number of newborn mature neurons in the ventral DG (reflecting in the whole DG), perhaps by impairing neuronal maturation and survival, and suggest that PLA2 inhibition reported in the hippocampus of Alzheimer disease subjects might partly contribute to the neurogenic abnormalities found in the DG in this disease.