Alleviation of Aβ-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model

Abstract

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 Ab-infused cognitive dysfunction mouse model. We demonstrated that HGF gene transfer significantly alleviated Ab-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-Ab therapy might be a new therapeutic option for the treatment of AD.

Plasma biomarkers of depressive symptoms in older adults

“…38, 39 Its expression continues in adulthood and it is induced by ischemic injury 40 and other disease processes, including AD. 41 HGF enhances long-term potentiation, 42 improves or attenuates ischemia-related memory deficits 43 and Aβ-induced behavioral impairment, 44 and has anxiolytic properties, 45 whereas its suppression increases anxiety and depressive behaviors in rodents. 46 To our knowledge, only two studies have investigated HGF in relation to depression in humans, one of which found significantly lower serum HGF levels among 26 people with major depression compared with 19 controls, 47 whereas the other study found no difference in HGF levels in 12 women with major depression and borderline personality disorder.…”

The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine

“…found that HGF gene transfer alleviated amyloid-β-induced cognitive impairment in mice, as evaluated by a behavioral test. 122) …”

Induction of Hepatocyte Growth Factor Production in Human Dermal Fibroblasts by Caffeic Acid Derivatives

“…[3][4][5][6][7] Moreover, it is suggested to regulate neuronal survival and seemed to be useful for AD treatment, considering the studies like showing gene transfer of HGF in a mouse model alleviate amyloid β induced cognitive impairment. 10) So, pharmacological approach including gene therapy to increase the HGF level in the brain is going on. Thus, HGF inducers may also be useful as therapeutic agent for AD treatment.…”

“…9) HGF is also thought to be useful for Alz heimer's disease (AD) therapy according to the recent study showing that gene transfer of HGF in a mouse model alleviate amyloid β induced cognitive impairment. 10) Thus, HGF may be useful for curing for intractable diseases including neurodegenerative diseases, and its inducers may also be useful as therapeutic agent. For example, interleukin-1, one of growth factors such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) are known to induce HGF production.…”

“…23) We also reported that CQAs and acteoside (2) possessed antiamyloidogenic effect. 24,25) With the raising interest studies these caffeic acid derivatives have a potential to promote production of HGF that is also suggested to regulate neuronal survival, 9,10) we performed HGF enzyme-linked immunosorbent assay (ELISA). Here, we describe caffeic acid derivatives like 4,5-di-O-caffeoylquinic acid (1) or acteoside (2) potently promoted HGF production in Neonatal Normal Human Dermal Fibroblasts (NHDF).…”