Brain Pathology

＜Laboratory of Neuronal Regeneration＞

＜Naoko Kaneko, M.D., Ph.D.＞

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After the end of embryonic development in mammals, neurons are not produced in most of the areas of the central nervous system. Neurons degenerated by insults cannot be replaced by new ones in the adult brain. However, in the ventricular-subventricular zone (V-SVZ) located at the lateral walls of the lateral ventricles, neurons are continuously generated even in the adult brain. We are focusing on the behavior of the young immature neurons under physiological and pathological conditions.

The V-SVZ-derived new neurons migrate for a long distance in mature brain tissues containing many glial cells and neuronal fibers to modify neuronal circuit. In addition, in response to brain insults such as ischemic stroke, neurodegenerative diseases and traumatic injury, neuroblasts migrate toward the damaged area to regenerate neurons. Thus, the V-SVZ can be an endogenous source of new neurons that contribute to the regeneration of neuronal circuitry. However, this spontaneous process does not produce adequate neurological restoration. We aim to understand the mechanisms that regulate migration and differentiation of the new neurons and their roles in brain plasticity and regeneration in the adult brain. We further investigate efficient interventions that manipulate these endogenous processes to cause functional recovery.

Research topics

1. Mechanisms regulating behavior of the V-SVZ-derived new neurons and their roles in the adult brain
2. Behaviors and roles of the adult-born new neurons in neuronal regeneration after brain injury
3. Interventions promoting neuronal regeneration

Selected publications

1. Kaneko N, Nakamura S, Sawamoto K. Effects of interferon-alpha on hippocampal neurogenesis and behavior in common marmosets. Molecular Brain 13: Article number: 98 (2020)
2. Akter M, Kaneko N, Herranz-Pérez V, Nakamura S, Oishi H, García-Verdugo JM, Sawamoto K. Dynamic changes in the neurogenic potential in the ventricular-subventricular zone of common marmoset during postnatal brain development. Cerebral Cortex 30, 4092-4109 (2020)
3. Kaneko N, Herranz-Pérez V, Otsuka T, Sano H, Ohno N, Omata T, Nguyen HB, Thai TQ, Nambu A, Kawaguchi Y, García-Verdugo JM, Sawamoto K. New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration. Science Advances 4, eaav0618 (2018)
4. Jinnou H, Sawada M, Kawase K, Kaneko N, Herranz-Pérez V, Miyamoto T, Kawaue T, Miyata T, Tabata Y, Akaike T, García-Verdugo JM, Ajioka I, Saitoh S, Sawamoto K. Radial glial fibers support neuronal migration and regeneration after neonatal brain injury. Cell Stem Cell 22, 128-137 (2018)
5. Fujioka T, Kaneko N, Ajioka I, Nakaguchi K, Omata T, Ohba H, Fässler R, García-Verdugo JM, Sekiguchi K, Matsukawa N, Sawamoto K. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain. EBioMedicine 16, 195-203 (2017)
6. Zheng LS, Kaneko N, Sawamoto K. Minocycline treatment ameliorates interferon-alpha- induced neurogenic defects and depression-like behaviors in mice. Frontiers in Cellular Neuroscience 9, 5 (2015)
7. Zheng LS, Hitoshi S, Kaneko N, Takao K, Miyakawa T, Tanaka Y, Xia H, Kalinke U, Kudo K, Kanba S, Ikenaka K, Sawamoto K. Mechanisms for Interferon-α-Induced Depression and Neural Stem Cell Dysfunction. Stem Cell Reports 3, 73–84 (2014)
8. Kako E, Kaneko N, Aoyama M, Hida H, Takebayashi H, Ikenaka K, Asai K, Togari H, Sobue K, Sawamoto K. Subventricular zone-derived oligodendrogenesis in injured neonatal white matter in mice enhanced by a nonerythropoietic erythropoietin derivative. Stem Cells 30, 2234-2247 (2012)
9. Sawada M, Kaneko N, Inada H, Wake H, Kato Y, Yanagawa Y, Kobayashi K, Nemoto T, Nabekura J, Sawamoto K. Sensory input regulates spatial and subtype-specific patterns of neuronal turnover in the adult olfactory bulb. Journal of Neuroscience 31, 11587-96 (2011)
10. Kaneko N, Marín O, Koike M, Hirota Y, Uchiyama Y, Wu J, Lu Q, Tessier-Lavigne M, Alvarez-Buylla A, Okano H, Rubenstein J, Sawamoto K. New neurons clear the path of astrocytic processes for their rapid migration in the adult brain. Neuron 67, 213-23 (2010)

Members

Naoko Kaneko M.D., Ph.D. (Principal investigator, Professor)
Mieko Morishima, Ph.D. (Research associate professor)
Yuriko Sobu, Ph.D. (Research assistant professor)

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