ABSTRACT
This in vitro study evaluated the detrimental effect of acute gamma (gamma)-irradiation on rat immature hippocampal neurons. Rat immature hippocampal neurons (0.5 day in vitro) were irradiated with 0~4 Gy gamma-rays. Cytotoxicity was analyzed using a lactate dehydrogenase release assay at 24 h after gamma-irradiation. Radiation-induced cytotoxicity in immature hippocampal neurons increased in a dose-dependent manner. Pre-treatments of pro-apoptotic caspase inhibitors and anti-oxidative substances significantly blocked gamma-irradiation-induced cytotoxicity in immature hippocampal neurons. The results suggest that the caspase-dependent cytotoxicity of gamma-rays in immature hippocampal cultured neurons may be caused by oxidative stress.
Subject(s)
Animals , Female , Pregnancy , Rats , Amifostine/pharmacology , Antioxidants/pharmacology , Caspase 3/metabolism , Catechin/analogs & derivatives , Cell Survival/radiation effects , Cells, Cultured/cytology , Dose-Response Relationship, Radiation , Gamma Rays , Hippocampus/cytology , L-Lactate Dehydrogenase/radiation effects , Neurons/cytology , Poly(ADP-ribose) Polymerases/drug effects , Rats, Sprague-DawleyABSTRACT
This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.
Subject(s)
Animals , Male , Mice , Acute Radiation Syndrome/drug therapy , Amifostine/pharmacology , Apoptosis/immunology , Gamma Rays/adverse effects , Hippocampus/immunology , Immunohistochemistry , In Situ Nick-End Labeling , Memory/radiation effects , Mice, Inbred ICR , Neurogenesis/immunology , Radiation-Protective Agents/pharmacologyABSTRACT
Inhibin, which is important for normal gonadal function, acts on the pituitary gonadotropins to suppress folliclestimulating hormone (FSH) secretion. The level and cellular localization of the inhibin isotypes, alpha, beta(A) and beta(B), in the testis of mice were examined during postnatal development in order to determine if inhibin expression is related to testicular maturation. Mouse testes were sampled on postnatal days (PNDs) 1, 3, 6, 18, 48 and 120, and analyzed by Western blotting and immunofluorescence. Western blot analysis showed very low levels of inhibin alpha, beta(A) and beta(B) expression in the testes at days 1 to 6 after birth. The levels then increased gradually from PND 18 to 48-120, and there were significant peaks at PND 48. Inhibin alpha, beta(A) and beta(B) were detected in testicular cells during postnatal development using immunohistochemistry. The immunoreactivity of inhibin alpha was rarely observed in testicular cells during PND 1 to 6, or in the cytoplasmic process of Sertoli cells surrounding the germ cells and interstitial cells during PND 18 to 120. Inhibin beta(A) and beta(B) immunoreactivity was rarely observed in the testis from PND 1 to 6. On the other hand, it was observed in some spermatogonial cells, as well as in the interstitial space between PND 48 and PND 120. We conclude that the expression of inhibin isotypes increases progressively in the testis of mice with increasing postnatal age, suggesting that inhibin is associated with a negative feedback signal for FSH in testicular maturation.