Chronic inhibition of brain phospholipase A(2) in adult rats impairs the survival of newborn mature neurons in the hippocampus

Autor(es)

Schaeffer, Evelin L. ^[1] ; Gattaz, Wagner F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, Lab Neurosci LIM 27, BR-05403010 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEURAL TRANSMISSION; v. 122, n. 5, p. 619-628, MAY 2015.
• Citações Web of Science: 2

Resumo

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 A(2) (PLA(2)) in neuronal differentiation/maturation and survival. This study aimed to investigate the effect of in vivo chronic inhibition of brain PLA(2) in adult rats on the number of newborn mature neurons in the DG. Male Wistar rats were injected with BrdU (cell proliferation marker) and 2 weeks later (beginning of neuronal maturation) sham-operated or infused intracerebroventricularly with either vehicle (DMSO in saline) or PLA(2) inhibitor (MAFP dissolved in the vehicle) for 14 days via osmotic minipump. The animals were euthanised 28 days 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 PLA(2) 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 PLA(2) inhibition reported in the hippocampus of Alzheimer disease subjects might partly contribute to the neurogenic abnormalities found in the DG in this disease. (AU)

• Processo FAPESP: 09/52825-8 - Neurobiologia da doença de Alzheimer: marcadores de risco, prognóstico e resposta terapêutica
• Beneficiário: Wagner Farid Gattaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/53008-3 - Efeitos da inibição crônica da fosfolipase A2 sobre a diferenciação de novos neurônios em células maduras no cérebro de ratos adultos
• Beneficiário: Evelin Lisete Schaeffer
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 10/05442-3 - Efeitos da inibição crônica da fosfolipase A2 sobre a diferenciação de novos neurônios em células maduras no cérebro de ratos adultos
• Beneficiário: Evelin Lisete Schaeffer
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores