Recombinant human NGF-loaded microspheres promote survival of basal forebrain cholinergic neurons and improve memory impairments of spatial learning in the rat model of Alzheimer's disease with fimbria-fornix lesion.
Neurotrophic factors are used for the experimental treatment of neurological disorders, such as Alzheimer's disease. However, delivery of the neurotrophic factors into the brain remains a big challenge. Recombinant human nerve growth factor (NGF)-loaded microspheres were fabricated and characterized in vitro and in vivo in our previous study. The present study was to assess the therapeutic benefit of rhNGF-loaded microspheres in treating the rat model of Alzheimer's disease with fimbria-fornix lesion. Recombinant human NGF-loaded microspheres were implanted into the basal forebrain of the rats with fimbria-fornix lesion. Four weeks after implantation in the basal forebrain, immunohistochemical analysis showed that rhNGF-loaded microspheres had a significant effect on the survival of axotomized cholinergic neurons in the medial septum (MS) and vertical diagonal branch (VDB) (p<0.05). Y-maze tests showed rhNGF-loaded microspheres can significantly improve the ability of spatial learning and memory of the rats with fimbria-fornix lesion (p<0.05). These results indicate that rhNGF-loaded microspheres are an effective means for the treatment of Alzheimer's disease.
Department of Histology and Embryology, Guangzhou Medical College, No. 195 Dongfeng Xilu, Guangzhou 510182, China. haigangg@hotmail.com
Haigang
H
Gu
Dahong
D
Long
Cunxian
C
Song
Xiaobin
X
Li
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D020712:Fornix, Brain / Q000473:pathology*; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008863:Microspheres; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D011994:Recombinant Proteins; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase