Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional recovery after stroke.
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.
Ishibashi
Satoru
S
Department of Neurology and Neurological Science, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Kuroiwa
Toshihiko
T
Sakaguchi
Masanori
M
Sun
Liyuan
L
Kadoya
Toshihiko
T
Okano
Hideyuki
H
Mizusawa
Hidehiro
H
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000166:cytology*; D004195:Disease Models, Animal; D007839:Functional Laterality; D037483:Galectin 1 / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D005849:Gerbillinae; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons; D011597:Psychomotor Performance / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects*; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D000906:Antibodies; D037483:Galectin 1; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine