Gender-dependent cellular and biochemical effects of maternal deprivation on the hippocampus of neonatal rats: a possible role for the endocannabinoid system.
Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal days (PND) 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. These behavioral impairments may be related to neuronal loss in the hippocampus triggered by elevated glucocorticoids. Furthermore, our previous data suggested functional relationships between MD stress and the endocannabinoid system. In this study, we addressed the effects of MD on hippocampal glial cells and the possible relationship with changes in plasma corticosterone (CORT) levels. In addition, we investigated the putative involvement of the endocannabinoid system by evaluating (a) the effects of MD on hippocampal levels of endocannabinoids (b) The modulation of MD effects by two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin (AA-5-HT), and the endocannabinoid reuptake inhibitor, OMDM-2. Drug treatments were administered once daily from PND 7 to PND 12 at a dose of 5 mg/kg, and the animals were sacrificed at PND 13. MD induced increased CORT levels in both genders. MD males also showed an increased number of astrocytes in CA1 and CA3 areas and a significant increase in hippocampal 2-arachidonoylglycerol. The cannabinoid compounds reversed the endocrine and cellular effects of maternal deprivation. We provide direct evidence for gender-dependent cellular and biochemical effects of MD on developmental hippocampus, including changes in the endocannabinoid system.
Llorente
Ricardo
R
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, Madrid, Spain.
Llorente-Berzal
Alvaro
A
Petrosino
Stefania
S
Marco
Eva-María
EM
Guaza
Carmen
C
Prada
Carmen
C
López-Gallardo
Meritxell
M
Di Marzo
Vincenzo
V
Viveros
María-Paz
MP
D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001593:Benzyl Compounds / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004334:Drug Administration Schedule; D063388:Endocannabinoids; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005989:Glycerides / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D001095:Arachidonic Acids; D001593:Benzyl Compounds; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005904:Glial Fibrillary Acidic Protein; D005989:Glycerides; C474343:OMDM-2 cpd; C114007:arachidonoylserotonin; D012701:Serotonin; C094503:glyceryl 2-arachidonate; D003345:Corticosterone