Adult generation of glutamatergic olfactory bulb interneurons

Brill, Monika S.; Ninkovic, Jovica; Winpenny, Eleanor; Hodge, Rebecca D.; Ozen, Ilknur; Yang, Roderick; Lepier, Alexandra; Gascón, Sergio; Erdélyi, Ferenc; Szabó, Gábor; Parras, Carlos; Guillemot, François; Frotscher, Michael; Berninger, Benedikt; Hevner, Robert F.; Raineteau, Olivier; Götz, Magdalena

doi:10.1038/nn.2416

Cited by 315 publications

(364 citation statements)

References 50 publications

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“…Moreover, antibodies directed against BDNF and SCF blocked the NSI‐189‐mediated rescue of cell viability against OGD. Similar reports have demonstrated cross‐talk between secreted factors (e.g., apoptosis, inflammation, oxidative stress) (; Brill et al, 2009; Chapman et al, 2015; Lu, Jones, Snyder, & Tuszynski, 2003; Zhang et al, 2015) and neurogenesis following brain insults, including stroke (Kernie and Parent, 2010; Yamashita et al, 2006). We (Hara et al, 2007; Morimoto et al, 2011; Tajiri et al, 2013), and others, have shown the important contribution of neurogenic factors in stroke brain remodeling (Jablonska et al, 2016; Rosell et al, 2013; Seo et al, 2014; Venna, Xu, Doran, Patrizz, & McCullough, 2014).…”

Section: Discussionmentioning

confidence: 54%

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

Tajiri

Quach

Kaneko

et al. 2017

Journal Cellular Physiology

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Enhancing neurogenesis may be a powerful stroke therapy. Here, we tested in a rat model of ischemic stroke the beneficial effects of NSI‐189, an orally active, new molecular entity (mol. wt. 366) with enhanced neurogenic activity, and indicated as an anti‐depressant drug in a clinical trial (Fava et al., 2015, Molecular Psychiatry, DOI: 10.1038/mp.2015.178) and being tested in a Phase 2 efficacy trial (ClinicalTrials.gov, 2016, ClinicalTrials.gov Identifier: NCT02695472) for treatment of major depression. Oral administration of NSI‐189 in adult Sprague–Dawley rats starting at 6 hr after middle cerebral artery occlusion, and daily thereafter over the next 12 weeks resulted in significant amelioration of stroke‐induced motor and neurological deficits, which was maintained up to 24 weeks post‐stroke. Histopathological assessment of stroke brains from NSI‐189‐treated animals revealed significant increments in neurite outgrowth as evidenced by MAP2 immunoreactivity that was prominently detected in the hippocampus and partially in the cortex. These results suggest NSI‐189 actively stimulated remodeling of the stroke brain. Parallel in vitro studies further probed this remodeling process and demonstrated that oxygen glucose deprivation and reperfusion (OGD/R) initiated typical cell death processes, which were reversed by NSI‐189 treatment characterized by significant attenuation of OGD/R‐mediated hippocampal cell death and increased Ki67 and MAP2 expression, coupled with upregulation of neurogenic factors such as BDNF and SCF. These findings support the use of oral NSI‐189 as a therapeutic agent well beyond the initial 6‐hr time window to accelerate and enhance the overall functional improvement in the initial 6 months post stroke.

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Section: Discussionmentioning

confidence: 54%

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

Tajiri

Quach

Kaneko

et al. 2017

Journal Cellular Physiology

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“…Indeed, in the cerebellum, inhibitory principal Purkinje neurons exhibit radial migration, whereas excitatory modulatory granule neurons migrate tangentially as well as radially (23). A very small number of glutamatergic modulatory interneurons are also generated in the adult SVZ and migrate tangentially to the olfactory bulb (24). Motor neurons in the spinal cord possess both radial and tangential migration (25).…”

Section: Discussionmentioning

confidence: 99%

Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

Sun

Zhou

Stadel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

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In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial "wholemount" dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system.

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“…After transcardial perfusion with phosphate buffered saline (PBS) followed by 4% paraformaldehyde (PFA) in PBS, brains were removed, postfixed in 4% PFA for 4 h at 4°C and processed for immunostainings or in situ hybridization (ISH), as described previously (Brill et al, 2009; Sirko et al 2013). Nuclei were visualized with 4′,6′‐diamidino‐2‐phenylindole (DAPI; 0.1 µg/mL; Sigma Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Sirko

Irmler

Gascón

et al. 2015

Glia

Self Cite

107

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Astrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring stem cell properties in vitro. In order to identify novel regulators of this subset, we performed genomewide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the gray matter of adult mouse cerebral cortex. The expression pattern was compared with astrocytes from intact cortex and adult neural stem cells (NSCs) isolated from the subependymal zone (SEZ). These comparisons revealed a set of genes expressed at higher levels in both endogenous NSCs and reactive astrocytes, including two lectins—Galectins 1 and 3. These results and the pattern of Galectin expression in the lesioned brain led us to examine the functional significance of these lectins in brains of mice lacking Galectins 1 and 3. Following stab wound injury, astrocyte reactivity including glial fibrillary acidic protein expression, proliferation and neurosphere‐forming capacity were found significantly reduced in mutant animals. This phenotype could be recapitulated in vitro and was fully rescued by addition of Galectin 3, but not of Galectin 1. Thus, Galectins 1 and 3 play key roles in regulating the proliferative and NSC potential of a subset of reactive astrocytes. GLIA 2015;63:2340–2361

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Adult generation of glutamatergic olfactory bulb interneurons

Cited by 315 publications

References 50 publications

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

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