title: Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.
abstract: Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.
authors.affiliation: Department of Psychiatry, Erzurum Regional Education and Research Hospital, Erzurum, Turkey.
authors.forename: Atakan
authors.initials: A
authors.lastname: Yucel
authors.affiliation: Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ataturk University, Erzurum, Turkey. Electronic address: md.nerminyucel@gmail.com.
authors.forename: Nermin
authors.initials: N
authors.lastname: Yucel
authors.affiliation: Department of Biochemistry, Faculty of Veterinary, Ataturk University, Erzurum, Turkey.
authors.forename: Seckin
authors.initials: S
authors.lastname: Ozkanlar
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Polat
authors.affiliation: Department of Histology and Embryology, Faculty of Veterinary, Ataturk University, Erzurum, Turkey.
authors.forename: Adem
authors.initials: A
authors.lastname: Kara
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Halil
authors.initials: H
authors.lastname: Ozcan
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gulec
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D053148:Caspase 3; D019253:Proto-Oncogene Proteins c-bcl-2; C084711:agomelatine; D009281:Naphthalenes; C505410:Casp3 protein, rat
keywords: Agomelatine; BDNF; Bcl-2; BrdU; Caspase-3; Hippocampus