Work

Kainic acid status epilepticus - induced changes in the hippocampus and hypothalamus alter the effects of exogenous Orexin-A in the hippocampus

Year: 2025

Type: article

Abstract: This study examined the effects of kainic acid–induced status epilepticus (KA-SE) on hippocampal and hypothalamic function, and evaluated the consequent alterations in the modulatory role of Orexin-A in the hippocampus. Behavioral experiments revealed cognitive and emotional impairments in KA-SE rats. In vivo electrophysiological recordings demonstrated a marked reduction in electrically evoked potentials (EEPs) in the CA1 region of KA-SE rats. Application of Orexin-A enhanced EEPs amplitude in CA1 and reduced it in CA3 of control animals, but elicited no effect in KA-SE rats. Orexin-A had no significant effects on the paired-pulse facilitation of EEPs in both the control and KA-SE groups indicating postsynaptic locus of its action. Morphological analysis demonstrated KA-SE–related neuronal loss in both the hippocampus and hypothalamus, including a significant reduction of GAD-positive interneurons in the CA3 of the hippocampus and Orexin-B–positive neurons in the hypothalamus. The observed reduction in GAD-positive neurons, which represent major targets of orexinergic input within the CA3 field, likely contributes to the impaired orexinergic modulation revealed in KA-SE animals. Our study reveals divergent orexinergic modulation in normal and epileptic hippocampal circuits, providing mechanistic insight into epilepsy-induced alterations of synaptic function.

Source: IBRO Neuroscience Reports

DOI: 10.1016/j.ibneur.2025.10.006

Authors: Tsira Kapanadze, Ekaterine Bakuradze, Gia Kutelia, Butsiko Chkhartishvili, Nanuli Doreulee

Institution: Tbilisi State University

Language: English

Topic: Epilepsy research and treatment

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,400