Alleviation of Abeta-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model.
A new therapeutic approach to treat Alzheimer's disease (AD) is needed, and the use of growth factors is considered to be a candidate. Hepatocyte growth factor (HGF) is a unique multifunctional growth factor, which has the potential effect to exert neurotrophic action and induce angiogenesis. In this study, we examined the effects of overexpression of human HGF plasmid DNA using ultrasound-mediated gene transfer into the brain in an Abeta-infused cognitive dysfunction mouse model. We demonstrated that HGF gene transfer significantly alleviated Abeta-induced cognitive impairment in mice in behavioral tests. These beneficial effects of HGF might be due to (1) significant recovery of the vessel density in the dentate gyrus of the hippocampus, (2) upregulation of BDNF, (3) a significant decrease in oxidative stress and (4) synaptic enhancement. A pharmacological approach including gene therapy to increase the HGF level in combination with anti-Abeta therapy might be a new therapeutic option for the treatment of AD.
Takeuchi
D
D
Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Japan.
Sato
N
N
Shimamura
M
M
Kurinami
H
H
Takeda
S
S
Shinohara
M
M
Suzuki
S
S
Kojima
M
M
Ogihara
T
T
Morishita
R
R
D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000235:genetics*; D006624:Hippocampus / Q000098:blood supply; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D015612:Phonophoresis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor