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Adult hippocampal neurogenesis plays an important role in health and disease. Regulating neurogenesis may be a key mechanism in the pathophysiology and treatment of several neurobehavioral disorders such as schizophrenia, depression, autism spectrum disorders and Alzheimer's disease. Cytokines are known to affect adult neurogenesis, but conflicting studies have been reported with regard to their actual role. Interleukine-17 (IL-17), a potent pro-inflammatory cytokine, has been shown to inhibit proliferation of neuroprogenitors and thus reduce hippocampal neurogenesis, while other studies suggested it can promote neurite outgrowth. In the present study we sought to explore the possible effect of a single dose administration of IL-17 on neurogenesis related behavior, i.e. spatial learning. Surprisingly, ICR mice injected with IL-17 (8 μg) had a significant slight improvement in spatial learning in the Morris water maze paradigm, without any changes in general locomotion compared with control mice. Indeed, the expression of neurogenesis related genes was down regulated following IL-17 treatment. However, we detected an upregulation in the expression of FGF-13, a gene promoting microtubule polymerization and neurite outgrowth, thus supporting neuronal maturation. We thus suggest that IL-17 has a complex role in regulating adult neurogenesis: inhibiting neuroprogenitors proliferation on one hand, while promoting maturation of already formed neuroblasts on the other hand. Our findings suggest that these roles can potentially affect neurogenesis related behavior. Its actual role in health and disease is yet to be determined.

In this study, we made use of dual-wavelength laser speckle imaging (DW-LSI) to assess cerebral blood flow (CBF) in the BTBR-genetic mouse model of autism spectrum disorder, as well as control (C57Bl/6J) mice. Since the deficits in social behavior demonstrated by BTBR mice are attributed to changes in neural tissue structure and function, we postulated that these changes can be detected optically using DW-LSI. BTBR mice demonstrated reductions in both CBF and cerebral oxygen metabolism (CMRO 2 ), as suggested by studies using conventional neuroimaging technologies to reflect impaired neuronal activation and cognitive function. To validate the monitoring of CBF by DW-LSI, measurements with laser Doppler flowmetry (LDF) were also performed which confirmed the lowered CBF in the autistic-like group. Furthermore, we found in vivo cortical CBF measurements to predict the rate of hippocampal neurogenesis, measured ex vivo by the number of neurons expressing doublecortin or the cellular proliferation marker Ki-67 in the dentate gyrus, with a strong positive correlation between CBF and neurogenesis markers (Pearson, r = 0.78; 0.9, respectively). These novel findings identifying cortical CBF as a predictive parameter of hippocampal neurogenesis highlight the power and flexibility of the DW-LSI and LDF setups for studying neurogenesis trends under normal and pathological conditions., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

Mesenchymal stem cells (MSCs) are known to enhance neurogenesis in the dentate gyrus, as well as to modulate immune cell activity and inflammation. Easily obtained and expanded from the bone marrow and other tissues, MSCs have been proposed as candidates for stem cell therapy in various neurodegenerartive diseases. In the present study, we sought to explore these therapeutic properties of MSC on Aß25-35-induced pathology when coadministered together. Apparently, coadministration of MSC prevented mild cognitive deficits observed following Aß administration alone, by promoting microglial activation and rapid clearance of injected Aß aggregates. Surprisingly, increased hippocampal neurogenesis was observed in the Aß-injected animals and was normal in MSC-coadministered animals just as in control animals. The observed increase in neurogenesis can be explained as a compensating mechanism responsible for the mild and temporary cognitive deficits observed in the Morris water maze assay in Aß-injected animals. Interestingly, MSC engrafted not only to the hippocampus but were also detected in the choroid plexus. We thus conclude that MSC may act in multiple pathways to protect the CNS from Aß pathology, while neurogenesis is a possible compensating mechanism; it is not always activated by MSC, which in turn may interact with local immune cells to regulate Aß accumulation.

Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10⁵ cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.