Downregulation of the LAR protein tyrosine phosphatase receptor is associated with increased dentate gyrus neurogenesis and an increased number of granule cell layer neurons.
Mol Cell Neurosci
; 31(4): 723-38, 2006 Apr.
Article
en En
| MEDLINE
| ID: mdl-16488625
ABSTRACT
Growth factors stimulating neurogenesis act through protein tyrosine kinases which are counterbalanced by protein tyrosine phosphatases (PTPs); thus, downregulation of progenitor PTP function might provide a novel strategy for promoting neurogenesis. We tested the hypotheses that the leukocyte common antigen-related (LAR) PTP is present in adult dentate gyrus progenitors, and that its downregulation would promote neurogenesis. In adult mice, LAR immunostaining was present in Ki-67- and PCNA-positive subgranular zone cells. At 1 h post-BrdU administration, LAR-/- mice demonstrated an approximately 3-fold increase in BrdU- and PCNA-positive cells, indicating increased progenitor proliferation. At 1 day and 4 weeks following 6 days of BrdU administration, LAR-/- mice exhibited a significant increase in BrdU and NeuN colabeled cells consistent with increased neurogenesis. In association with increased neurogenesis in LAR-/- mice, stereological analysis revealed a significant 37% increase in the number of neurons present in the granule cell layer. In cultured progenitor clones derived from LAR+/+ mice, LAR immunostaining was present in PCNA- and BrdU-positive cells. Progenitor clones derived from adult LAR-/- hippocampus or LAR+/+ clones made LAR-deficient with LAR siRNA demonstrated increased proliferation and, under differentiation conditions, increased proportions of Tuj1- and MAP2-positive cells. These studies introduce LAR as the first PTP found to be expressed in dentate progenitors and point to inhibition of LAR as a potential strategy for promoting neurogenesis. These findings also provide a rare in vivo demonstration of an association between increased dentate neurogenesis and an expanded population of granule cell layer neurons.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Fosfatasas
/
Receptores de Superficie Celular
/
Giro Dentado
/
Hipocampo
/
Proteínas del Tejido Nervioso
/
Neuronas
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Neurosci
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos