Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors.
The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.
Department of Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid, E-28040 Madrid, Spain.
Ana Belén
AB
López Rodríguez
Beatriz
B
Mateos Vicente
Silvana Y
SY
Romero-Zerbo
Noé
N
Rodriguez-Rodriguez
María José
MJ
Bellini
Fernando
F
Rodriguez de Fonseca
Francisco Javier
FJ
Bermudez-Silva
Iñigo
I
Azcoitia
Luis M
LM
Garcia-Segura
María-Paz
MP
Viveros
D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis; D002186:Cannabinoids / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology* / Q000517:prevention & control*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists; D043882:Receptors, Cannabinoid / Q000187:drug effects*; D013238:Stereotaxic Techniques; D016707:Tissue Fixation; D014746:Vimentin / Q000494:pharmacology; D014951:Wounds, Stab / Q000473:pathology
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D014746:Vimentin; C103505:AM 251; D004958:Estradiol; C094023:iodopravadoline