Early maternal deprivation induces changes on the expression of 2-AG biosynthesis and degradation enzymes in neonatal rat hippocampus.
Early maternal deprivation (MD) in rats (24h, PND 9-10) is a model for neurodevelopmental stress. Our previous data showed that MD altered the hippocampal levels of the endocannabinoid 2-AG and the expression of hippocampal cannabinoid receptors in 13-day-old rats, with males being more markedly affected. The aim of this study was to analyze the impact of MD on the enzymes involved in 2-AG biosynthesis (DAGLalpha and DAGLbeta) and degradation (MAGL) in relevant areas (DG, CA1, CA3) of the hippocampus in 13-day-old neonatal rats. The expression of the enzymes was evaluated by quantitative RT-PCR, immunohistochemistry, and densitometry. MD induced a significant increase in DAGLalpha immunoreactivity in both males and females, which was mainly associated with fibers in the polymorphic cell layer of the dentate gyrus and in the stratum pyramidale of CA3. In contrast, the molecular layer of the dentate gyrus showed a significant decrease in DAGLalpha immunoreactivity in MD males and females. No changes were observed in DAGLbeta immunoreactivity. MD induced a significant decrease in MAGL immunoreactivity in hippocampal CA3 and CA1 areas, more marked in males than in females, and that was mainly associated with fibers in all strata of CA3 and CA1. The results also showed a significant decrease of MAGL mRNA levels in MD males. These data support a clear association between neurodevelopmental stress and dysregulation of the endocannabinoid system. This association may be relevant for schizophrenia and other neurodevelopmental psychiatric disorders.
Suárez
Juan
J
Laboratorio de Medicina Regenerativa, Fundación IMABIS, Hospital Carlos Haya, 29010 Málaga, Spain. juan.suarez@fundacionimabis.org
Rivera
Patricia
P
Llorente
Ricardo
R
Romero-Zerbo
Silvana Y
SY
Bermúdez-Silva
Francisco J
FJ
de Fonseca
Fernando Rodríguez
FR
Viveros
María-Paz
MP
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D008071:Lipoprotein Lipase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D008994:Monoacylglycerol Lipases / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors
D012333:RNA, Messenger; D008994:Monoacylglycerol Lipases; D008071:Lipoprotein Lipase