genetic knockdown of brain-derived neurotrophic factor in 3xtg-ad mice does not alter aβ or tau pathology脑源性神经营养因子的基因击倒在3 xtg-ad老鼠不改变aβ或τ病理学.pdfVIP

Genetic Knockdown of Brain-Derived Neurotrophic Factor in 3xTg-AD Mice Does Not Alter Ab or Tau Pathology Nicholas A. Castello1,2, Kim N. Green1,2, Frank M. LaFerla1,2* 1 Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America, 2 Department of Neurobiology and Behavior, University of California Irvine, Irvine, California, United States of America Abstract Brain-derived neurotrophic factor (BDNF) is a neurotrophin critically involved in cell survival, synaptic plasticity, and memory. BDNF has recently garnered significant attention as a potential therapeutic target for neurodegenerative diseases such as Alzheimer disease (AD), but emerging evidence suggests that BDNF may also be mechanistically involved in the pathogenesis of AD. AD patients have substantially reduced BDNF levels, which may be a result of Ab and tau pathology. Recent evidence, however, indicates reduced BDNF levels may also serve to drive pathology in neuronal cultures, although this has not yet been established in vivo. To further investigate the mechanistic role of BDNF in AD, we generated 3xTg-AD mice with a heterozygous BDNF knockout (BDNF+/ 2) and analyzed Ab and tau pathology. Aged 3xTg-AD/BDNF+/ 2 mice have significantly reduced levels of brain BDNF, but have comparable levels of Ab and tau pathology to 3xTg-AD/BDNF+/+ mice. These findings indicate that chronic reduction of BDNF does not exacerbate the development of Ab and tau pathology, and instead suggests the reduced BDNF levels found in AD patients are a consequence of these pathologies. Citation: Castello NA, Green KN, LaFerla FM (2012) Genetic Knockdown of Brain-Derived Neurotrophic Factor in 3xTg-AD Mice Does Not Alter Ab or Tau Pathology. PLoS ONE 7(8): e39566. doi:10.1371/journal.pone.0039566 Editor: Steph