title: D-methionine protects against cisplatin-induced neurotoxicity in the hippocampus of the adult rat.
abstract: The hippocampus plays an important role in memory, mood, and spatial navigation. In the dentate gyrus of the adult hippocampus, in the subgranular zone (SGZ), new cells are generated, which differentiate and mature into new neurons. Cisplatin, a highly effective antineoplastic drug with nephrotoxic and ototoxic side effects, induces apoptosis and suppresses neurogenesis in the hippocampus leading to memory impairment. Previous studies have shown that the antioxidant D-methionine protects against cisplatin-induced ototoxicity and nephrotoxicity suggesting that it might also prevent neurogenesis from being suppressed by cisplatin treatment. To test this hypothesis, rats were treated with cisplatin, D-methionine, cisplatin plus D-methionine, or saline (controls). Seven days after treatment, the rats were sacrificed, and hippocampal sections immunolabeled for doublecortin (DCX) to identify neuronal precursor cells and maturing neurons in the SGZ. Cisplatin significantly reduced the number of DCX-labeled cells (~80 %) relative to controls. In contrast, DCX cell counts in rats treated with D-methionine prior to cisplatin were similar to controls. The treatment with D-methionine alone did not affect the number of DCX cells. These results indicate that D-methionine prevents the dramatic cisplatin-induced decrease of neurogenesis.
authors.affiliation: Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main St, Buffalo, NY, 14214, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Hinduja
authors.forename: Kari Suzanne
authors.initials: KS
authors.lastname: Kraus
authors.forename: Senthilvelan
authors.initials: S
authors.lastname: Manohar
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Salvi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage; D002945:Cisplatin / Q000633:toxicity*; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D058953:Neural Stem Cells / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D008715:Methionine; D002945:Cisplatin