[P2-89] The developmental changes of Nav1.2 in human brain
[Aim] To observe the developmental changes of Nav1.2 and its colocalization with parvalbumin in human brain, and analyze their relationship with related epilepsies.
[Methodology] The archived human brain tissue, obtained from 36 autopsy cases, aging from 13 weeks of gestation (GW) to 63 years of age (Y), were involved. Nav1.2 mono-staining immunohistochemistry (IHC) and Nav1.2-Parvalbumin double staining IHC were performed, following with comparative microscopic analysis and quantitative image analysis. Western blotting was also performed on 5 non-epilepsy patients’ temporal lobe extraction aging from 23GW to 59Y.
[Results] Nav1.2 showed heterogeneous distribution patterns and distinct developmental changes in human brain. The most dramatic developmental changes occurred during fetus and the first year of life, especially noticeable in the cerebellar cortex, quantitative image analysis showed same trend. At the same time, Nav1.2 showed high colocalization rate with Parvalbumin in extensive brain regions. Western blotting detected positive signals since 40GW and increased with development.
[Conclusions] Nav1.2 developmental changes somewhat coincided with the course of benign familial neonatal-infantile seizures (BFNIS), providing a plausible explanation for the age dependence of BFNIS. The high colocalization rate of Nav1.2 and Parvalbumin in extensive brain regions imply Nav1.2 may have extensively synergistic effect with Parvalbumin-positive interneurons in human brain. The integrative regulation of the developmental expression of Nav1.2 and other ion channels, modifying or interacting proteins that alter neuronal excitability, may play an important role in the pathogenesis of BFNIS and (or) other Nav1.2-related epilepsy syndromes.
[Methodology] The archived human brain tissue, obtained from 36 autopsy cases, aging from 13 weeks of gestation (GW) to 63 years of age (Y), were involved. Nav1.2 mono-staining immunohistochemistry (IHC) and Nav1.2-Parvalbumin double staining IHC were performed, following with comparative microscopic analysis and quantitative image analysis. Western blotting was also performed on 5 non-epilepsy patients’ temporal lobe extraction aging from 23GW to 59Y.
[Results] Nav1.2 showed heterogeneous distribution patterns and distinct developmental changes in human brain. The most dramatic developmental changes occurred during fetus and the first year of life, especially noticeable in the cerebellar cortex, quantitative image analysis showed same trend. At the same time, Nav1.2 showed high colocalization rate with Parvalbumin in extensive brain regions. Western blotting detected positive signals since 40GW and increased with development.
[Conclusions] Nav1.2 developmental changes somewhat coincided with the course of benign familial neonatal-infantile seizures (BFNIS), providing a plausible explanation for the age dependence of BFNIS. The high colocalization rate of Nav1.2 and Parvalbumin in extensive brain regions imply Nav1.2 may have extensively synergistic effect with Parvalbumin-positive interneurons in human brain. The integrative regulation of the developmental expression of Nav1.2 and other ion channels, modifying or interacting proteins that alter neuronal excitability, may play an important role in the pathogenesis of BFNIS and (or) other Nav1.2-related epilepsy syndromes.