Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiology of Disease, 31, 316-326

Univ Montpellier 2, Montpellier, F-34095, France.
Neurobiology of Disease (Impact Factor: 5.2). 08/2008; 31(3):316-26. DOI: 10.1016/j.nbd.2008.05.012
Source: PubMed

ABSTRACT We examined the potential protective effect of BDNF against beta-amyloid-induced neurotoxicity in vitro and in vivo in rats. In neuronal cultures, BDNF had specific and dose-response protective effects on neuronal toxicity induced by Abeta(1-42) and Abeta(25-35). It completely reversed the toxic action induced by Abeta(1-42) and partially that induced by Abeta(25-35). These effects involved TrkB receptor activation since they were inhibited by K252a. Catalytic BDNF receptors (TrkB.FL) were localized in vitro in cortical neurons (mRNA and protein). In in vivo experiments, Abeta(25-35) was administered into the indusium griseum or the third ventricle and several parameters were measured 7 days later to evaluate potential Abeta(25-35)/BDNF interactions, i.e. local measurement of BDNF release, number of hippocampal hilar cells expressing SRIH mRNA and assessment of the corpus callosum damage (morphological examination, pyknotic nuclei counting and axon labeling with anti-MBP antibody). We conclude that BDNF possesses neuroprotective properties against toxic effects of Abeta peptides.

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    • "exhibit decreased BDNF levels in these regions ( Phillips et al . , 1991 ; Murray et al . , 1994 ; Amoureux et al . , 1997 ) , which is mirrored by reduced blood serum BDNF levels in AD patients ( Laske et al . , 2006 ) . In vitro experiments demonstrated that BDNF exerts several neuroprotective effects by reducing the cytotoxic effects of Aβ 42 ( Arancibia et al . , 2008 ) and by stimulating the non - amyloidogenic pathway , resulting in a reduction of toxic Aβ species ( Scheuner et al . , 1996 ; Fu et al . , 2002 ; Nishitomi et al . , 2006 ; Thornton et al . , 2006 ; Rohe et al . , 2009 ) . In rodent and primate models of AD it has been shown that acute application of BDNF protein can partially rescue "
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    ABSTRACT: There is increasing evidence that brain-derived neurotrophic factor (BDNF) plays a crucial role in AD pathology. A number of studies demonstrated that AD patients exhibit reduced BDNF levels in the brain and the blood serum, and in addition, several animal-based studies indicated a potential protective effect of BDNF against Aβ-induced neurotoxicity. In order to further investigate the role of BDNF in the etiology of AD, we created a novel mouse model by crossing a well-established AD mouse model (APP/PS1) with a mouse exhibiting a chronic BDNF deficiency (BDNF+/-). This new triple transgenic mouse model enabled us to further analyze the role of BDNF in AD in vivo. We reasoned that in case BDNF has a protective effect against AD pathology, an AD-like phenotype in our new mouse model should occur earlier and/or in more severity than in the APP/PS1-mice. Indeed, the behavioral analysis re-vealed that the APP/PS1-BDNF+/--mice show an earlier onset of learning impairments in a two-way active avoidance task in comparison to APP/PS1- and BDNF+/--mice. However in the Morris water maze test, we could not observe an overall aggrevated impairment in spatial learning and also short-term memory in an object recognition task remained intact in all tested mouse lines. In addition to the behavioral experiments, we analyzed the amyloid plaque pa-thology in the APP/PS1 and APP/PS1-BDNF+/--mice and observed a comparable plaque den-sity in the two genotypes. Moreover, our results revealed a higher plaque density in prefrontal cortical compared to hippocampal brain regions. Our data reveal that higher cognitive tasks requiring the recruitment of cortical networks appear to be more severely affected in our new mouse model than learning tasks requiring mainly sub-cortical networks. Furthermore, our observations of an accelerated impairment in active avoidance learning in APP/PS1-BDNF+/--mice further supports the hypothesis that BDNF deficiency amplifies AD-related cognitive dysfunctions.
    Frontiers in Behavioral Neuroscience 03/2015; 9:00058. DOI:10.3389/fnbeh.2015.00058 · 4.16 Impact Factor
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    • "Based on that, they stated that such phenomenon possibly occurs due to a compensatory mechanism that would happen in the initial stages of dementia. The increase in BDNF in vivo could represent an attempt to rescue neurons from damage and diminish the amyloid burden since it was able to reverse the toxic effect of Ab in vitro (Arancibia et al., 2008). Laske et al. (2006) proposed that peripheral levels of BDNF would increase in the early stages of dementia and decrease according to the severity of the neurodegeneration. "
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    • "BDNF mRNA and protein are decreased in post-mortem brain tissue from subjects with mild cognitive impairment (MCI) and AD (Connor et al., 1997; Ferrer et al., 1999; Garzon et al., 2002; Hock et al., 2000; Holsinger et al., 2000; Michalski and Fahnestock, 2003; Peng et al., 2005; Phillips et al., 1991), and the reduction in BDNF correlates with the degree of cognitive impairment (Peng et al., 2005). BDNF administration can rescue synaptic loss and cognitive dysfunction in animal models, implicating loss of BDNF as a contributing factor to AD (Arancibia et al., 2008; Blurton-Jones et al., 2009; Nagahara et al., 2009). Down-regulation of BDNF does not exacerbate Ab deposition or tau pathology in a 3X transgenic mouse model of Alzheimer's "
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