Author(s): Machlusil Husna, Kusworini Handono, Hidayat Sujuti, Aulanni’am Aulanni’am, Afiyfah Kiysa Waafi, Rumman Karimah, Alya Satira

Email(s): machlusilhusna.fk@ub.ac.id

DOI: 10.52711/0974-360X.2024.00192   

Address: Machlusil Husna1,2*, Kusworini Handono3, Hidayat Sujuti4, Aulanni’am Aulanni’am5, Afiyfah Kiysa Waafi6, Rumman Karimah6, Alya Satira6
1Doctoral Program in Medical Science, Faculty of Medicine Universitas Brawijaya, East Java, Indonesia
2Department of Neurology, Faculty of Medicine Universitas Brawijaya, Saiful Anwar General Hospital, Malang, East Java, Indonesia
3Department of Clinical Pathology, Faculty of Medicine Universitas Brawijaya, Saiful Anwar General Hospital, Malang, East Java, Indonesia.
4Department of Ophthalmology, Faculty of Medicine Universitas Brawijaya, Saiful Anwar General Hospital, Malang, East Java, Indonesia.
5Department of Biochemistry, Laboratory of Biochemistry, Faculty of Sciences Universitas Brawijaya, East Malang, Java, Indonesia.
6Master Program in Biomedical Sciences, Faculty of Medicine Universitas Brawijaya, Malang, East Java, Indonesia. *Corresponding Author

Published In:   Volume - 17,      Issue - 3,     Year - 2024


ABSTRACT:
Despite the development of anti-epilepsy drugs, drug-refractory epilepsy still becomes a challenging problem along with an increased incidence of epilepsy. To face that challenge and increase patients’ quality of life, treatment of epilepsy must effectively prevent epileptogenesis, not only symptomatic treatment. AKT signaling pathway was proven to have important roles in epilepsy through its function in the synaptic plasticity, neurogenesis, axon guidance, modulation of the glutamate transporter, and activation of the Ca2+ channel. AKT also activated mTOR signaling pathway as activator of mTORC1 and also effector of mTORC2. Several studies showed the ability of long-term rapamycin treatment to inhibit mTORC2. This study used organotypic hippocampal slice cultures (OHSC) and long-term rapamycin treatment was administered for 3, 5, 8, and 10 days at a dose of 20 nM after induction of epilepsy by low-Mg2+ medium administration for 40 minutes. Low-Mg2+ medium administration induced seizure activity in OHSC showed by significant increase in intracellular Ca2+expressionand also significantly increase AKT activity. After administration of long-term rapamycin treatment AKT activity and intracellular Ca2+expression were significantly reduced. The longer the treatment of rapamycin, the lower the AKT activity and intracellular Ca2+expression. Long-term rapamycin treatment has the potential to become a novel epilepsy drug through its ability to attenuate AKT activity and suppress the seizures proven by lower intracellular Ca2+expression.


Cite this article:
Machlusil Husna, Kusworini Handono, Hidayat Sujuti, Aulanni’am Aulanni’am, Afiyfah Kiysa Waafi, Rumman Karimah, Alya Satira. Long-term Rapamycin Treatment Inhibit AKT Activity and Lower Intracellular Calcium Expression in Organotypic Hippocampal Slice Cultures Model of Epilepsy. Research Journal of Pharmacy and Technology. 2024; 17(3):1232-9. doi: 10.52711/0974-360X.2024.00192

Cite(Electronic):
Machlusil Husna, Kusworini Handono, Hidayat Sujuti, Aulanni’am Aulanni’am, Afiyfah Kiysa Waafi, Rumman Karimah, Alya Satira. Long-term Rapamycin Treatment Inhibit AKT Activity and Lower Intracellular Calcium Expression in Organotypic Hippocampal Slice Cultures Model of Epilepsy. Research Journal of Pharmacy and Technology. 2024; 17(3):1232-9. doi: 10.52711/0974-360X.2024.00192   Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2024-17-3-43


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