Altered Electroencephalography Spectral Profiles in Rats with Different Patterns of Experimental Brain Dysplasia

Abstract

To our knowledge, this constitutes the first quantitative description of power spectral properties in this experimental model, providing insight into mechanisms underlying the anatomical and electrophysiological abnormalities associated with brain dysplasia of different types. Birth Defects Research, 110:303-316, 2018. © 2017 Wiley Periodicals, Inc.

Profiles of gene expression in the hippocampal formation of rats with experimentally‐induced brain dysplasia

“…There is also the possibility of other cellular populations being affected by Nr2f2 dysregulation, as this factor has also recently been identified in astrocytes from methyl-CpG binding protein 2 (Mecp2) deficient mice, a model of Rett's syndrome (Del epine et al, 2015). On a similar note, Rfx3-deficient mice belong to a family of animal models of primary ciliopathies, resulting in agenesis of the corpus callosum, albeit with only partial penetrance, which is intriguingly similar to the frequency of such abnormalities reported by our group previously in rats irradiated at E13 (Edwards et al, 2014;Kielbinski et al, 2018). Finally, there is evidence of dysregulated inflammation, through both the suppression of repressor genes (e.g., Rasgrp1, Gab1) and powerful upregulation of Cybb, exacerbated further in animals challenged with pilocarpine.…”

“…Previously, we have reported that the pattern of prenatal irradiation‐induced dysplasia related to the time of insult (from E13 to E19) may be associated with different susceptibility to seizures (Setkowicz et al, ). In a recent study, we have extended this view by finding differences in the extent of structural anomalies in MRI, in EEG spectral composition, as well as expression of astrocytic markers in the hippocampus (Kielbinski et al, ). These time points correspond to critical events in the development of the brain in general, and the hippocampal formation in particular.…”

“…Indeed, behavioral studies in prenatally irradiated rats have shown evidence of deficits in spatial memory and cue recognition tasks which heavily involve the hippocampus, as well as reduced neuronal connectivity in the structure (Zhou et al, 2011;Zhou and Roper, 2012). In a recent study (Kielbinski et al, 2018) we have also found altered hippocampal levels of glial proteins potentially involved in epilepsy, such as connexin 43 and Kir4.1, as well as glutamate receptor subunit Glur4.…”

“…The genes from cluster C in our analysis are all upregulated in animals from the E13 group, which are characterized by more profound anatomical abnormalities, such as significantly reduced brain and hippocampal volume, high incidence of large periventricular heterotopias or dysgenesis of the corpus callosum (Kielbinski et al, 2018). Cybb (cytochrome b-245, beta polypeptide) is a proinflammatory protein controlling microglial function, related to oxidative stress and angiogenesis (Surace and Block, 2012).…”

“…A number of anatomical and functional anomalies in the hippocampal formation are universally reported across developmental models of MCD, including pyramidal and granular layer dispersion, abnormalities in connectivity and electrophysiological properties of hippocampal neurons or deficits in glial marker expression. Behavioral testing commonly also reveals deficits in tests and tasks related to hippocampal memory and spatial processing (Kielbinski et al, 2018;Lucas et al, 2011;Ouardouz and Carmant, 2012;Threlkeld et al, 2009;Tschuluun et al, 2005;Zhou et al, 2011;Zhou and Roper, 2012).…”