Neural stem cells (NSCs) persist in defined brain niches, including the subventricular zone (SVZ), throughout adulthood and generate new neurons destined to support specific neurological functions. Whether brain diseases such as multiple sclerosis (MS) are associated with changes in adult NSCs and whether this might contribute to the development and/or persistence of neurological deficits remains poorly investigated. We examined SVZ function in mice in which we targeted an MS-like pathology to the forebrain. In these mice, which we refer to herein as targeted EAE (tEAE) mice, there was a reduction in the number of neuroblasts compared with control mice. Altered expression of the transcription factors Olig2 and Dlx2 in the tEAE SVZ niche was associated with amplification of pro-oligodendrogenic transit-amplifying cells and decreased neuroblast generation, which resulted in persistent reduction in olfactory bulb neurogenesis. Altered SVZ neurogenesis led to impaired long-term olfactory memory, mimicking the olfactory dysfunction observed in MS patients. Importantly, we also found that neurogenesis was reduced in the SVZ of MS patients compared with controls. Thus, our findings suggest that neuroinflammation induces functional alteration of adult NSCs that may contribute to olfactory dysfunction in MS patients.
Vanja Tepavčević, Françoise Lazarini, Clara Alfaro-Cervello, Christophe Kerninon, Kazuaki Yoshikawa, José Manuel Garcia-Verdugo, Pierre-Marie Lledo, Brahim Nait-Oumesmar, Anne Baron-Van Evercooren
Title and authors | Publication | Year |
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Activation of endogenous neural stem cells for multiple sclerosis therapy
I Michailidou, HE de Vries, EM Hol, ME van Strien |
Frontiers in neuroscience | 2015 |
Effects of inflammation on stem cells: together they strive?
C Kizil, N Kyritsis, M Brand |
EMBO reports | 2015 |
Alteration of synaptic connectivity of oligodendrocyte precursor cells following demyelination
A Sahel, FC Ortiz, C Kerninon, PP Maldonado, MC Angulo, B Nait-Oumesmar |
Frontiers in cellular neuroscience | 2015 |
Neurogenic niches in the brain: help and hindrance of the barrier systems
HB Stolp, Zà Molnár |
Frontiers in neuroscience | 2015 |
Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis: Gal-3 Role in the SVZ After TMEV
RE James, J Hillis, I Adorján, B Gration, MV Mundim, AJ Iqbal, MM Majumdar, RL Yates, MM Richards, GE Goings, GC DeLuca, DR Greaves, SD Miller, FG Szele |
Glia | 2015 |