Rolipram promotes hippocampal regeneration in mice after trimethyltin-induced neurodegeneration.

Autor: Sakurai M; Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi., Imaizumi M; Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi., Sakai Y; Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan., Morimoto M; Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi.
Jazyk: angličtina
Zdroj: Neuroreport [Neuroreport] 2024 Sep 04; Vol. 35 (13), pp. 832-838. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1097/WNR.0000000000002072
Abstrakt: This study aimed to investigate the effects of rolipram, a phosphodiesterase inhibitor, on brain tissue regeneration. Trimethyltin-injected mice, an animal model of hippocampal tissue regeneration, was created by a single injection of trimethyltin chloride (2.2 mg/kg, intraperitoneally). Daily rolipram administration (10 mg/kg, intraperitoneally) was performed from the day after trimethyltin injection until the day before sampling. In Experiment 1, brain samples were collected on day 7 postinjection of trimethyltin following the forced swim test. In Experiment 2, bromodeoxyuridine (150 mg/kg, intraperitoneally/day) was administered on days 3-5 and sampling was on day 21 postinjection of trimethyltin. Samples were routinely embedded in paraffin and sections were obtained for histopathological investigation. In Experiment 1, rolipram-treated mice showed shortened immobility times in the forced swim test. Histopathology revealed that rolipram treatment had improved the replenishment of neuronal nuclei-positive neurons in the dentate gyrus, which was accompanied by an increase in the percentage of phosphorylated cyclic AMP response element-binding protein-positive cells. In addition, rolipram had decreased the percentage of ionized calcium-binding adapter protein 1-positive microglia with activated morphology and the number of tumor necrosis factor-alpha-expressing cells. In Experiment 2, double immunofluorescence for bromodeoxyuridine/neuronal nuclei revealed an increase of double-positive cells in rolipram-treated mice. These results demonstrate that rolipram effectively promotes brain tissue regeneration by enhancing the survival of newborn neurons and inhibiting neuroinflammation.
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Databáze: MEDLINE