Neurobiology of Disease

Univ Montpellier 2, Montpellier, F-34095, France.
Neurobiology of Disease (Impact Factor: 5.08). 08/2008; 31(3):316-26. DOI: 10.1016/j.nbd.2008.05.012
Source: PubMed


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 · 3.27 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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    ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Neurotrophic factors and inflammatory markers may play considerable roles in AD. In this study we measured, through Enzyme-Linked Immunosorbent Assay, the plasma levels of brain derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and neuronal growth factor (NGF), as well as tumor necrosis factor-alpha soluble receptors, sTNFR1 and sTNFR2, and soluble intercellular adhesion molecule 1 (sICAM-1), in 50 AD patients, 37 patients with mild cognitive impairment (MCI) and 56 healthy elderly controls. BDNF levels, expressed as median and interquartile range, were higher for AD patients (2545.3, 1497.4-4153.4 pg/ml) compared to controls (1503.8, 802.3-2378.4 pg/ml), P < 0.001. sICAM-1 was also higher in AD patients. sTNFR1 levels were increased in AD when compared to controls and also to MCI. GDNF, NGF and sTNFR2 levels showed no significant differences among the studied groups. The increase in BDNF might reflect a compensatory mechanism against early neurodegeneration and seems to be related to inflammation. sTNFR1 appears to mark not only the inflammatory state but also differentiates between MCI and AD, which may be an additional tool for differentiating degrees of cognitive impairment.
    Journal of Psychiatric Research 02/2014; 53(1). DOI:10.1016/j.jpsychires.2014.01.019 · 3.96 Impact Factor
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    • "Even if there have been conflicting results regarding the expression of BDNF in AD patients [32], most of the results indicate that BDNF is severely decreased in the hippocampus and some cortical areas [7,33]. Meanwhile, BDNF could reduce cellular damage caused by Aβ1-42 [34]. Our results showed that EA treatment significantly increased the expression of BDNF in both the hippocampus and cortex; this suggests that the increase in BDNF may be involved in the therapeutic effect of EA for AD. "
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    ABSTRACT: Alzheimer's disease (AD) is a severe neurodegenerative disease for which there is currently no effective treatment. The purpose of this study was to investigate whether repeated electroacupuncture (EA) stimulation would improve cognitive function and the pathological features of AD in amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice. Cognitive function of APP/PS1 double transgenic mice was assessed using the Morris water maze test before and after EA treatment. Levels of amyloid beta-peptide (Abeta) deposits in the hippocampus and cortex were evaluated by immunofluorescence, western blot and enzyme-linked immunosorbent assay. Expression of brain-derived neurotrophic factor (BDNF) was also examined by immunofluorescence and western blot. The neurogenesis was labeled by the DNA marker bromodeoxyuridine. EA stimulation significantly ameliorated the learning and memory deficits of AD mice by shortening escape latency and increasing the time spent in the target zone during the probe test. Additionally, decreased Abeta deposits and increased BDNF expression and neurogenesis in the hippocampus and cortex of EA-treated AD mice were detected. The same change was detected in wild-type mice after EA treatment compared with wild-type mice without EA treatment. Repeated EA stimulation may improve cognitive function, attenuate Abeta deposits, up-regulate the expression of BDNF and promote neurogenesis in the APP/PS1 double transgenic mice. This suggests that EA may be a promising treatment for AD.
    BMC Complementary and Alternative Medicine 01/2014; 14(1):37. DOI:10.1186/1472-6882-14-37 · 2.02 Impact Factor
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