title: Allopregnanolone prevents memory impairment: effect on mRNA expression and enzymatic activity of hippocampal 3-α hydroxysteroid oxide-reductase.
abstract: In this work we investigated how the neurosteroid allopregnanolone can modulate learning and memory processes. For this purpose, we used ovariectomized (OVX) rats subcutaneously injected with oestradiol benzoate (E) alone or E and progesterone (P). Then, rats were injected in dorsal hippocampus with allopregnanolone or vehicle. Animals were tested in inhibitory avoidance task (IA task). After behavioural test hippocampal mRNA expression and enzymatic activity of 3α-HOR, the enzyme responsible of allopregnanolone synthesis, were analysed. In IA task OVX-EP rats spent less time on platform, compared to those OVX or OVX-E. Regression analyses revealed that there was a significant negative relationship between E-P infusion and performance in this task. Pre-training allopregnanolone administration to OVX-EP rats increased the time spent on the platform. Interestingly, when enzymatic activity of 3α-HOR was tested, OVX-EP rats showed a significant decrease in the enzymatic activity, compared with OVX and OVX-E rats. In addition, OVX-EP group showed a significant increase in the enzymatic activity after intrahippocampal infusion of allopregnanolone. On the other hand, when mRNA expression of 3α-HOR was analysed no differences were observed when the hippocampal allopregnanolone injection was done. These results suggest that E and P have amnesic effects on female rats, being reversed by allopregnanolone through its modulation on hippocampal 3α-HOR activity.
authors.affiliation: Instituto de Investigaciones Biomédicas (INBIOMED), Universidad de Mendoza (IMBECU-CONICET), Paseo Dr. Emilio Descote 720, 5500 Mendoza, Argentina.
authors.forename: Carla
authors.initials: C
authors.lastname: Escudero
authors.forename: Sebastián
authors.initials: S
authors.lastname: Casas
authors.forename: Fernando
authors.initials: F
authors.lastname: Giuliani
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bazzocchini
authors.forename: Sebastián
authors.initials: S
authors.lastname: García
authors.forename: Roberto
authors.initials: R
authors.lastname: Yunes
authors.forename: Ricardo
authors.initials: R
authors.lastname: Cabrera
mesh_terms: D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004958:Estradiol / Q000633:toxicity; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007266:Inhibition, Psychological; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects; D010052:Ovariectomy; D011280:Pregnanolone / Q000627:therapeutic use*; D011374:Progesterone / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D011280:Pregnanolone; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)