17Beta-estradiol protects depletion of rat temporal cortex somatostatinergic system by beta-amyloid.
Estradiol prevents amyloid-beta peptide (Abeta)-induced cell death through estrogen receptors (ERs) and modulates somatostatin (SRIF) responsiveness in the rat brain. As intracerebroventricular (ICV) Abeta25-35 administration reduces SRIFergic tone in the temporal cortex of ovariectomized (Ovx) rats, we asked whether 17beta-estradiol (E2) treatment can restore the Abeta25-35 induced changes in SRIF content, SRIF receptor density and adenylyl cyclase (AC) activity, as well as if these effects are mediated by ERs. E2 treatment did not change Abeta25-35 levels in the temporal cortex, but partially restored the SRIFergic parameters affected by Abeta insult and decreased cell death, which was correlated with Akt activation. The ER antagonist ICI 182,780 prevented the protective effect of E2 on sst2 levels, but did not modify SRIF levels. Furthermore, ICI 182,780 treatment further decreased sst2 protein and mRNA levels when administered alone to Abeta25-35-treated rats, suggesting that it may block the effects of endogenous estrogens. These findings indicate that E2 protects the temporal cortical SRIFergic system from Abeta-induced depletion independently of Abeta accumulation.
Aguado-Llera
David
D
Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Avda. Menéndez Pelayo, Madrid, Spain.
Arilla-Ferreiro
Eduardo
E
Chowen
Julie A
JA
Argente
Jesús
J
Puebla-Jiménez
Lilian
L
Frago
Laura M
LM
Barrios
Vicente
V
D000262:Adenylyl Cyclases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D020287:In Situ Nick-End Labeling; D010052:Ovariectomy / Q000379:methods; D010446:Peptide Fragments / Q000008:administration & dosage*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism*; D013702:Temporal Lobe / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D004965:Estrogen Antagonists; D010446:Peptide Fragments; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C074636:amyloid beta-protein (25-35); D000077267:Fulvestrant; D004958:Estradiol; D013004:Somatostatin; D000262:Adenylyl Cyclases