Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer\'s disease (Nat Med, 2009, doi:10.10398/nm.1912)

報告日期: 2009/05/08
報告時間: 17:10/18:00
報告學生: 陳建仲
講評老師: 郭余民
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980508-3.pdf

Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease

Nature Medicine15:331-337, 2009.

 

Speaker : Chien-Chung Chen( 陳建仲 )

Commentator : Yu-Min Kuo ( 郭余民 老師 )

Time : 17:00 ~ 18:00 May 08, 2009

Place : Room 602

 

Alzheimer’s disease (AD) is the most common neuronal dysfunction disease in aging brain. It includes neurodegeneration in entorhinal cortex which contributes to the early loss of short-term memory. So far AD cannot be cured efficiently and treatments for delaying or halting the progression of the disease are still not available. There are some evidences that Brain-derived neurotrophic factor (BDNF) protein levels were reported to be decreased in the entorhinal cortex of patients with AD. BDNF supports cholinergic, dopaminergic, 5-hydroxytryptamine, and neuropeptides containing neurons. BDNF also implicated in plasticity mechanisms hypothesized to underlie learning through supporting the survival of existing neurons and encourage the growth and differentiation of new neurons and synapses. Which raises the possibilities that overexpression of BDNF through AD entorhinal cortex may ameliorate entorhinal cortex and hippocampus degeneration in models related to Alzheimer’s disease? Here the authors showed a broad and profound neuroprotective effects of direct lentiviral overexpression of BDNF into entorhinal cortex in several animal models of AD, which may go through the therapeutic restoration of degenerated hippocampal neurons. In APP-transgenic mice, BDNF application had no effect on the level of Aβ accumulation however it significantly improved the behavior performance, synaptic molecules activation and gene expression levels when treatment initiated after the onset of disease. The dysregulated expression levels of Mfge8, Galk2 Stl3 related to the metabolism and clearance of Aβwhich found to be down regulated in AD were corrected after BDNF gene delivery. These restorative effects of BDNF are scalable to nonhuman privates, not only the cell number in the aged brain but also learning performance had an obvious advancement. These findings provided a possible way to cure and delay the progression of AD.

 

Reference:

Lucia Tapia-Arancibia, Esteban Aliaga, Michelle Silhol and Sandor Arancibia (2008) New insights into brain BDNF function in normal aging and Alzheimer disease, Brain Research Reviews 59:201-220.