Does astrocyte gap junction protein expression differ during development in absence epileptic rats?

Abstract

Intercellular communication via gap junctions (GJs) has a wide variety of complex and essential functions in the CNS. In the present developmental study, we aimed to quantify the number of astrocytic GJs protein connexin 30 (Cx30) of genetic model of absence epilepsy rats from Strasbourg (GAERS) at postnatal P10, P30, and P60 days in the epileptic focal areas involved in the cortico-thalamic circuit. We compared the results with Wistar rats using immunohistochemistry and western blotting. The number of Cx30 immunopositive astrocytes per unit area were quantified for the somatosensory cortex (SSCx), ventrobasal (VB), and lateral geniculate (LGN) thalamic nuclei of the two strains and Cx30 western blot was applied to the tissue samples from the same regions. Both immunohistochemical and western blot results revealed the presence of Cx30 in all regions studied at P10 in both Wistar and GAERS animals.The SSCx, VB, and LGN of Wistar animals showed progressive increase in the number of Cx30 immunopositive labeled astrocytes from P10 to P30 and reached a peak at P30; then a significant decline was observed from P30 to P60 for the SSCx and VB. However, in GAERS Cx30 immunopositive labeled astrocytes showed a progressive increase from P10 to P60 for all brain regions studied. The immunohistochemical data highly corresponded with western blotting results. We conclude that the developmental disproportional expression of Cx30 in the epileptic focal areas in GAERS may be related to the onset of absence seizures or may be related to the neurogenesis of absence epilepsy.

Thalamocortical circuits in generalized epilepsy: Pathophysiologic mechanisms and therapeutic targets

“…Interactions between astrocytes and neurons in the development of generalized seizures could be bidirectional. For instance, in various IGE models ( Akbar et al, 1998 ; Dutuit et al, 2000 ; Dutuit et al, 2002 ; Cavdar et al, 2019 ; Kose et al, 2022 ; Thompson et al, 2022 ), as well as in some models of DEEs (Scn8a epileptic encephalopathy Thompson et al, 2022 , Dravet syndrome Uchino et al, 2023 ), thalamic astrocytes proliferate and take on a reactive phenotype – downregulating glutamate and GABA transporters, and decreasing potassium uptake – while spontaneous seizures develop. Experimental work has now extended these observations and established a role for thalamic astrocytes in thalamocortical circuit physiology and generalized seizures.…”