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Open AccessArticle

Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

1
Drug Discovery Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
2
Laboratory of Cell Migration and Invasion, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
3
Laboratory of Cancer Personalized Medicine and Diagnostic Genomics, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 1133; https://doi.org/10.3390/ijms21031133
Received: 19 January 2020 / Revised: 4 February 2020 / Accepted: 5 February 2020 / Published: 8 February 2020
(This article belongs to the Special Issue CNS Drug Action in Neurodegenerative Diseases)
Adult neurogenesis is a complex physiological process, which plays a central role in maintaining cognitive functions, and consists of progenitor cell proliferation, newborn cell migration, and cell maturation. Adult neurogenesis is susceptible to alterations under various physiological and pathological conditions. A substantial decay of neurogenesis has been documented in Alzheimer’s disease (AD) patients and animal AD models; however, several treatment strategies can halt any further decline and even induce neurogenesis. Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. To better evaluate this effect, we chronically administered an arginase inhibitor, norvaline, to triple-transgenic and wild-type mice, and applied an advanced immunohistochemistry approach with several biomarkers and bright-field microscopy. Remarkably, we evidenced a significant reduction in the density of neuronal progenitors, which demonstrate a different phenotype in the hippocampi of triple-transgenic mice as compared to wild-type animals. However, norvaline showed no significant effect upon the progenitor cell number and constitution. We demonstrated that norvaline treatment leads to an escalation of the polysialylated neuronal cell adhesion molecule immunopositivity, which suggests an improvement in the newborn neuron survival rate. Additionally, we identified a significant increase in the hippocampal microtubule-associated protein 2 stain intensity. We also explore the molecular mechanisms underlying the effects of norvaline on adult mice neurogenesis and provide insights into their machinery. View Full-Text
Keywords: Alzheimer’s disease; neurogenesis; norvaline; arginase; arginine; NO Alzheimer’s disease; neurogenesis; norvaline; arginase; arginine; NO
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Polis, B.; Srikanth, K.D.; Gurevich, V.; Bloch, N.; Gil-Henn, H.; Samson, A.O. Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice. Int. J. Mol. Sci. 2020, 21, 1133.

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