Abstract
Neurodevelopmental impairment can affect lifelong brain functions such as cognitive and social behaviour, and may contribute to aging-related changes of these functions. In the present study, we hypothesized that bone marrow-derived mesenchymal stem cells (MSC) administration may repair neurodevelopmental behavioural deficits by modulating adult hippocampal neurogenesis. Indeed, postnatal intracerebral transplantation of MSC has restored cognitive and social behaviour in mice prenatally exposed to valproic acid (VPA). MSC transplantation also restored post-developmental hippocampal neurogenesis, which was impaired in VPA-exposed mice displaying delayed differentiation and maturation of newly formed neurons in the granular cell layer of the dentate gyrus. Importantly, a statistically significant correlation was found between neuronal differentiation scores and behavioural scores, suggesting a mechanistic relation between the two. We thus conclude that post-developmental MSC administration can overcome prenatal neurodevelopmental deficits and restore cognitive and social behaviours via modulation of hippocampal adult neurogenesis.
Highlights
A growing body of evidence links neurodevelopmental changes, in neurogenesis in particular, with lifelong changes in cognition and behaviour [1, 2]
Transplantation of mesenchymal stem cells improves behavioural deficits caused by prenatal valproic acid (VPA) exposure
In the spatial learning assay (Morris Water Maze [MWM] test), the VPA-treated mice exhibited an impaired learning behaviour, as was evident by a longer escape latency durations on the third day onward of the trial compared with untreated mice (Figure 2A)
Summary
A growing body of evidence links neurodevelopmental changes, in neurogenesis in particular, with lifelong changes in cognition and behaviour [1, 2]. Neurodevelopmental impairment trajects on future neural functions but may share pathological mechanisms with age-related neurobehavioral disorders [3, 4]. Understanding these mechanisms and applying proper interventions may have implications for the neurodevelopmental disorders per se but for the maintenance of lifelong mental health as well. In attempt to correct the impaired neurogenesis and associated pathologies, the transplantation of mesenchymal stem cells (MSC) has been proposed and tested in several models [7]. We and others have shown that intracerebral transplantation of MSC can increase adult hippocampal neurogenesis and improve the related impaired behaviour such as cognitive, social and depressive-like behaviours [10,11,12,13,14,15]
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