Nestin‐expressing cell types in the temporal lobe and hippocampus: Morphology, differentiation, and proliferative capacity

Abstract

Nestin is expressed in immature neuroepithelial and progenitor cell types and transiently upregulated in proliferative neuroglial cells responding to acute brain injury, including following seizures. In 36 temporal lobe (TLobe) specimens from patients with TLobe epilepsy (age range 8–60 years) we studied the number, distribution and morphology of nestin‐expressing cells (NEC) in the pes, hippocampus body, parahippocampal gyrus, amygdala, temporal cortex and pole compared with post mortem control tissues from 26 cases (age range 12 gestational weeks to 76 years). The proliferative fraction of NEC was evaluated in selected regions, including recognized niches, using MCM2. Their differentiation was explored with neuronal (DCX, mushashi, βIII tubulin, NeuN) and glial (GFAP, GFAPdelta, glutamine synthetase, aquaporin4, EAAT1) markers, both in sections or following culture. Findings were correlated with clinical parameters. A stereotypical pattern in the distribution and morphologies of NEC was observed, reminiscent of patterns in the developing brain, with increased densities in epilepsy than adult controls (p < .001). Findings included MCM2‐positive radial glial‐like cells in the periventricular white matter and rows of NEC in the hippocampal fimbria and sulcus. Nestin cells represented 29% of the hippocampal proliferative fraction in epilepsy cases; 20% co‐expressed βIII tubulin in culture compared with 28% with GFAP. Significant correlations were noted between age at surgery, memory deficits and nestin populations. TLobe NEC with ongoing proliferative capacity likely represent vestiges of developmental migratory streams and resident reactive cell populations of potential relevance to hippocampal epileptogenesis, TLobe pathology, and co‐morbidities, including memory decline.

Granule Cell Dispersion in Human Temporal Lobe Epilepsy: Proteomics Investigation of Neurodevelopmental Migratory Pathways

“…markers (Myelin Basic Protein, MBP) were also detected in all samples, consistent with immunohistochemical findings (Figure 1E). The expression of GFAP was comparable between basal and dispersed samples and was slightly higher in younger than older samples; of interest, the expression of vimentin, expressed in immature astrocytes, was predominantly observed in basal and younger samples ( Figure 2D) in keeping with our previous studies (Liu et al, 2018). The expression of connexion 43, a gap junction protein expressed in astrocytes, was similar to the expression of GFAP.…”

Spatiotemporal dynamics of PDGFRβ expression in pericytes and glial scar formation in penetrating brain injuries in adults

“…The morphology of Olig2/MCM2 + remained ‘oligo‐like’ with no definite evidence of glial/pericyte maturation; however, no double labelling of Olig2 with nestin or PDGFRβ was performed in the present study. We have also recently identified nestin + radial glial cell types in adult temporal lobe with regenerative capacity, glial maturation in vitro and focal co‐localization with PDGFRβ . Heterogeneous populations of regenerative parenchymal cells could therefore potentially contribute to astroglial scar formation following injury.…”

Nestin in immature embryonic neurons regulates axon growth cone morphology and Semaphorin3a sensitivity

“…We conclude that nestin protein is indeed expressed in immature neurons in culture. Close reading of the literature revealed that nestin protein has been detected in neurons in human and mouse, both in early differentiating neurons (Walker et al 2007;Yan et al 2001;Cattaneo & McKay 1990;Crews et al 2011;Messam et al 2002;Messam et al 1999), and in subpopulations of adult neurons (Gu et al 2002;Hendrickson et al 2011;Decimo et al 2011;Guo et al 2014;Liu et al 2018). Recent advances in single cell western blotting have revealed persistent nestin expression in βIII tubulin positive differentiated neural stem cells (Hughes et al 2014).…”