Environmental enrichment rescues memory in mice deficient for the polysialytransferase ST8SiaIV

Abstract

The neural cell adhesion molecule NCAM and its association with the polysialic acid (PSA) are believed to contribute to brain structural plasticity that underlies memory formation. Indeed, the attachment of long chains of PSA to the glycoprotein NCAM down-regulates its adhesive properties by altering cell-cell interactions. In the brain, the biosynthesis of PSA is catalyzed by two polysialyltransferases, which are differentially regulated during lifespan. One of them, ST8SiaIV (PST), is predominantly expressed during adulthood whereas the other one, ST8SiaII (STX), dominates during embryonic and post-natal development. To understand the role played by ST8SiaIV during learning and memory and its underlying hippocampal plasticity, we used knockout mice deleted for the enzyme ST8SiaIV (PST-ko mice). At adult age, PST-ko mice show a drastic reduction of PSA-NCAM expression in the hippocampus and intact hippocampal adult neurogenesis. We found that these mice display impaired long-term but not short-term memory in both, spatial and non-spatial behavioral tasks. Remarkably, memory deficits of PST-ko mice were abolished by exposure to environmental enrichment that was also associated with an increased number of PSA-NCAM expressing new neurons in the dentate gyrus of these mice. Whether the presence of a larger pool of immature, likely plastic, new neurons favored the rescue of long-term memory in PST-ko mice remains to be determined. Our findings add new evidence to the role played by PSA in memory consolidation. They also suggest that PSA synthesized by PST critically controls the tempo of new neurons maturation in the adult hippocampus.

Dose‐dependent neurocognitive deficits following postnatal day 10 HIV‐1 viral protein exposure: Relationship to hippocampal anatomy parameters

“…Thus, the results from both studies suggest that spatial learning and/or memory deficits following HIV‐1 viral protein exposure may be due to increased gliosis and/or neuronal loss in the DGH. Previous work has found associations between the DGH and spatial learning and/or memory in multiple disease models, (Zhang et al, 2011; Martinez‐Canabal et al, 2013; Cahill et al, 2014; Piazza et al, 2014; Taylor et al, 2015; Zerwas et al, 2015), supporting the findings of the present study.…”

News and Views on Polysialic Acid: From Tumor Progression and Brain Development to Psychiatric Disorders, Neurodegeneration, Myelin Repair and Immunomodulation

“…A related finding is the increase of DCX-positive progenitors in the SGZ of St8sia4 -deficient mice ( Nacher et al, 2010 ). More recently, it could be demonstrated that memory deficits of St8sia4 knockout mice in a novel object recognition task could be overcome by environmental enrichment ( Zerwas et al, 2016 ). St8sia4 deficiency had no effect on neurogenesis per se, but environmental enrichment was associated with an increased number of polySia-positive cells in the SGZ, i.e., of early progenitors with an ST8SIA2-dependent polySia production.…”