Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional recovery after stroke

Exp Neurol. 2007 Oct;207(2):302-13. doi: 10.1016/j.expneurol.2007.06.024. Epub 2007 Jul 17.

Abstract

Galectin-1 (Gal-1) has recently been identified as a key molecule that plays important roles in the regulation of neural progenitor cell proliferation in two neurogenic regions: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. To test the hypothesis that Gal-1 contributes to adult neurogenesis after focal ischemia, we studied the temporal profile of endogenous Gal-1 expression and the effects of human recombinant Gal-1 on neurogenesis and neurological functions in an experimental focal ischemic model. In the normal brain, Gal-1 expression was observed only in the SVZ. In the ischemic brain, Gal-1 expression was markedly upregulated in the SVZ and the area of selective neuronal death around the infarct in the striatum. The temporal profile of Gal-1 expression was correlated with that of neural progenitor cell proliferation in the SVZ of the ischemic hemisphere. Double-labeling studies revealed that Gal-1 was localized predominantly in both reactive astrocytes and SVZ astrocytes. Administration of Gal-1, which is known to have carbohydrate-binding ability, into the lateral ventricle increased neurogenesis in the ipsilateral SVZ and improved sensorimotor dysfunction after focal ischemia. By contrast, blockade of Gal-1 in the SVZ by the administration of anti-Gal-1 neutralizing antibody strongly inhibited neurogenesis and diminished neurological function. These results suggest that Gal-1 is one of the principal regulators of adult SVZ neurogenesis through its carbohydrate-binding ability and provide evidence that Gal-1 protein has a role in the improvement of sensorimotor function after stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Behavior, Animal
  • Body Weight / drug effects
  • Brain Infarction / etiology
  • Brain Infarction / pathology
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Proliferation / drug effects*
  • Cerebral Ventricles / cytology*
  • Disease Models, Animal
  • Functional Laterality
  • Galectin 1 / administration & dosage*
  • Galectin 1 / immunology
  • Galectin 1 / metabolism
  • Gerbillinae
  • Male
  • Maze Learning / drug effects
  • Motor Activity / drug effects
  • Nerve Tissue Proteins / metabolism
  • Neurons
  • Psychomotor Performance / drug effects
  • Recovery of Function / drug effects*
  • Stroke / complications
  • Stroke / drug therapy*
  • Stroke / pathology

Substances

  • Antibodies
  • Galectin 1
  • Nerve Tissue Proteins
  • Bromodeoxyuridine