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Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS). A complex pathophysiological process referred to as epileptogenesis transforms a normal brain into an epileptic one. Prevention of epileptogenesis is a subject of intensive research. Currently, there are no clinically approved drugs that can act as preventive medication. Our previous studies have revealed highly promising antiepileptogenic properties of a compound–myo-inositol (MI) and the present research broadens previous results and demonstrates the long-term disease-modifying effect of this drug, as well as the amelioration of cognitive comorbidities. For the first time, we show that long-term treatment with MI: (i) decreases the frequency and duration of electrographic SRS in the hippocampus; (ii) has an ameliorating effect on spatial learning and memory deficit associated with epileptogenesis, and (iii) attenuates cell loss in the hippocampus. MI treatment also alters the expression of the glial fibrillary acidic protein, LRRC8A subunit of volume-regulated anion channels, and protein tyrosine phosphatase receptor type R, all expected to counteract the epileptogenesis. All these effects are still present even 4 weeks after MI treatment ceased. This suggests that MI may exert multiple actions on various epileptogenesis-associated changes in the brain and, therefore, could be considered as a candidate target for prevention of epileptogenesis.

The present research aimed to study the effects of selective immunolesions of cholinergic or gamma-aminobutyric acid (GABA)ergic neurons in the nucleus basalis magnocellularis (NBM) on memory function as well as cholinergic activity and the level of expression of glutamatergic [NR2B subunit of N-methyl-D-aspartate(NMDA)] receptors in the medial prefrontal cortex (mPFC) and hippocampus of behaviorally characterized rats. In behavioral experiments, working memory was assessed by a spatial alternation testing procedure in a plus-maze, and acquisition and retention of spatial memory was evaluated in a Morris water maze. The rats were divided into three groups: the NBM cholinergic, GABAergic immunolesioned groups and the normal control group. Cholin acetyltransferase or parvalbumin staining of the NBM and acetylcholinesterase staining of the mPFC and hippocampal sections were performed to visualize the effects of immunotoxins. The electrophoresis and immunoblotting were run to evaluate the effect of NBM lesions on the amount of the NR2B subunit of NMDA receptors. The results indicate that the immunolesion of cholinergic NBM neurons impair spatial working memory, as well as long-term spatial memory which is accompanied by significant changes in glutamatergic (the NR2B subunit of NMDA receptor) and cholinergic markers in the mPFC, whereas immunolesion of GABAergic NBM neurons does not affect long-term spatial memory, it does though cause the impairment of working memory with a reduction of the NMDA NR2B receptor signaling in the mPFC. The present results demonstrate that the cholinergic and GABAergic NBM cell groups play diverse and complementary roles and are integrated in distinct NBM-mPFC networks that may play different roles in mPFC memory function.

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