Neural Stem Cells Improve Memory in an Inducible Mouse Model of Neuronal Loss

Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 11/2007; 27(44):11925-33. DOI: 10.1523/JNEUROSCI.1627-07.2007
Source: PubMed


Neuronal loss is a major pathological outcome of many common neurological disorders, including ischemia, traumatic brain injury, and Alzheimer disease. Stem cell-based approaches have received considerable attention as a potential means of treatment, although it remains to be determined whether stem cells can ameliorate memory dysfunction, a devastating component of these disorders. We generated a transgenic mouse model in which the tetracycline-off system is used to regulate expression of diphtheria toxin A chain. After induction, we find progressive neuronal loss primarily within the hippocampus, leading to specific impairments in memory. We find that neural stem cells transplanted into the brain after neuronal ablation survive, migrate, differentiate and, most significantly, improve memory. These results show that stem cells may have therapeutic value in diseases and conditions that result in memory loss.

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Available from: Mathew Blurton-Jones, Nov 26, 2015
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    • "No examples of fully matured GFP/NeuN double-labeled neurons were detected (Figure S1). Taken together, these findings are consistent with previous reports that murine NSCs predominantly acquire gliogenic phenotypes when transplanted into non-neurogenic regions and with other studies that utilized these postnatal day 1-derived cells (Herrera et al., 1999; Yamasaki et al., 2007; Blurton-Jones et al., 2009). Interestingly, no significant differences in NSC differentiation were detected between ASO and WT transplanted mice (Figure 1I), and each cell type migrated with similar distribution and distance from the injection site (Figure S1A). "
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    • "Also transplantation of glial-restricted progenitor cells & olfactory ensheathing stem cells (OESCs) shows positive effects in the survival of the ALS disease[65,66]. Loss of neurotrophic factors & growth factors (including GDNF, BDNF, VEGF, and IGF-1) has been implicated in the pathogenesis of ALS[67]. These factors play a neuroprotective role for motor neurons also physical exercise appeared to be beneficial in animal experiments68697071. "
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    • "To study the adaptive response of the hippocampus following neuronal loss, we used the innovative CaM/Tet-DTA mouse model that induces hippocampal neuronal loss [32], [33]. This double transgene system consists of a transactivator driven by a constitutively active CaM-KII-alpha promoter, which in turns drive expression of a diphtheria toxin. "
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