title: Partial neuroprotection by 17-β-estradiol in neonatal γ-irradiated rat cerebellum.
abstract: Acute and long-term complications can occur in patients receiving radiation therapy. It has been suggested that cytoprotection might decrease the incidence and severity of therapy-related toxicity in these patients. Developing cerebellum is highly radiosensitive and for that reason it is a useful structure to test potential neuroprotective substances to prevent radiation induced abnormalities. Recent studies have shown that estrogen can rapidly modulate intracellular signalling pathways involved in cell survival. Thus, it has been demonstrated that estrogens mediate neuroprotection by promoting growth, cell survival and by preventing axonal pruning. The aim of this work was to evaluate the effect of the treatment with 17-β-estradiol on the motor, structural and biochemical changes induced by neonatal ionizing radiation exposure, and to investigate the participation of nitric oxide and protein kinase C, two important intracellular messengers involved in neuronal activity. Our results show that perinatal chronic 17-β-estradiol treatment partially protects against radiation-induced cerebellar disorganization and motor abnormalities. PKC and NOS activities could be implicated in its neuroprotective mechanisms. These data provide new evidence about the mechanisms underlying estrogen neuroprotection, which could have therapeutic relevance for patients treated with radiotherapy.
authors.affiliation: 1ª Cátedra de Farmacología-Centro de Investigaciones Farmacológicas y Botánicas Facultad de Medicina, Universidad de Buenos Aires-CONICET, Paraguay 2155, Piso 15, 1121 Buenos Aires, Argentina. mariazorrillaz@gmail.com
authors.forename: Maria A
authors.initials: MA
authors.lastname: Zorrilla Zubilete
authors.forename: Laura R
authors.initials: LR
authors.lastname: Guelman
authors.forename: Damian G
authors.initials: DG
authors.lastname: Maur
authors.forename: Lucila G
authors.initials: LG
authors.lastname: Caceres
authors.forename: Hugo
authors.initials: H
authors.lastname: Rios
authors.forename: Luis M
authors.initials: LM
authors.lastname: Zieher
authors.forename: Ana M
authors.initials: AM
authors.lastname: Genaro
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001925:Brain Damage, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D002526:Cerebellar Diseases / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005720:Gamma Rays; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D004958:Estradiol