Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy
Hiroshi Ueno,
Atsumi Shimada,
Shunsuke Suemitsu,
Shinji Murakami,
Naoya Kitamura,
Kenta Wani,
Yu Takahashi,
Yosuke Matsumoto,
Motoi Okamoto,
Takeshi Ishihara
Affiliations
Hiroshi Ueno
Department of Medical Technology, Kawasaki University of Medical Welfare, Okayama, 701-0193, Japan; Corresponding author at: Department of Medical Technology, Kawasaki University of Medical Welfare, 288, Matsushima, Kurashiki, Okayama, 701-0193, Japan.
Atsumi Shimada
Division of Food and Nutrition, Nakamura Gakuen University Junior College, Fukuoka, 814-0198, Japan
Shunsuke Suemitsu
Department of Psychiatry, Kawasaki Medical School, Okayama, 701-0192, Japan
Shinji Murakami
Department of Psychiatry, Kawasaki Medical School, Okayama, 701-0192, Japan
Naoya Kitamura
Department of Psychiatry, Kawasaki Medical School, Okayama, 701-0192, Japan
Kenta Wani
Department of Psychiatry, Kawasaki Medical School, Okayama, 701-0192, Japan
Yu Takahashi
Department of Psychiatry, Kawasaki Medical School, Okayama, 701-0192, Japan
Yosuke Matsumoto
Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan
Motoi Okamoto
Department of Medical Technology, Graduate School of Health Sciences, Okayama University, Okayama, 700-8558, Japan
Takeshi Ishihara
Department of Psychiatry, Kawasaki Medical School, Okayama, 701-0192, Japan
Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear.Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules.Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production.
