An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer's disease

Murer, Mario Gustavo; Boissière, Florence; Qiao, Yan; Hunot, Stéphane; Villares, Joào; Faucheux, Baptiste; Agid, Yves; Hirsch, Étienne C.; Raisman‐Vozari, Rita

doi:10.1016/s0306-4522(98)00219-x

Cited by 168 publications

(98 citation statements)

References 86 publications

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“…Reduced BDNF levels 39,40 Increasing BDNF & NGF levels is beneficial in disease models [51][52][53][54] Increased p75 NTR levels and signalling 75,172 Decreased Trk receptor levels and signalling 75,172 Increased Gsk3ß activity 66,173 Altered ERK activity 174 Reduced velocity and efficiency of axonal transport of BDNF 65,66 Apoptotic pathways Increased caspase-6 activity 89,90 Caspase-6 cleavage of disease proteins [89][90][91][92] Preventing caspase cleavage of disease proteins is beneficial in mouse models 93,94 Posttranslational modifications Palmitoylation of disease proteins is linked to aggregate formation 118,119 Phosphorylation of disease proteins reduces their cleavage by caspases 105,106 HDAC inhibition is beneficial in disease models 69,126,127 Protein aggregation and clearance mechanisms Misfolding and aggregation of disease proteins 128 UPS impairment 144,145 Impaired autophagy 161 Upregulation of autophagy is beneficial in disease models 153,155,156,158,162,163,165,167,<...>…”

Section: Supplementary Materialsmentioning

confidence: 99%

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Ehrnhoefer

Wong

Hayden

2011

Nat Rev Drug Discov

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Neurodegenerative diseases exemplified by Alzheimer's and Huntington disease are characterized by the progressive neuropsychiatric dysfunction and loss of specific neuronal subtypes. Even though there are differences in the exact sites of pathology and clinical profiles only partially overlap, considerable similarities in disease mechanisms and pathogenic pathways can be observed. These shared mechanisms raise the possibility of common therapeutic targets for drug development. Huntington disease with a monogenic cause and the possibility to accurately identify pre-manifest mutation carriers could be exploited as a 'model' for Alzheimer's disease to test the efficacy of therapeutic interventions targeting shared pathogenic pathways.

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Section: Supplementary Materialsmentioning

confidence: 99%

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Ehrnhoefer

Wong

Hayden

2011

Nat Rev Drug Discov

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“…Could such events precipitate limbic seizures of pilocarpine-treated rats with sprouting? Furthermore, could BDNF contribute to seizures in temporal lobe epilepsy, given that human mossy fibers express BDNF (Murer et al, 1999), temporal lobe epileptics demonstrate mossy fiber sprouting (Sutula et al, 1989), and human granule cells express increased BDNF mRNA after seizures (Mathern et al, 1997)? Certainly these are tempting conclusions, but they would be premature.…”

Section: Implications For Understanding Spontaneous Seizures In Sproumentioning

confidence: 99%

Actions of Brain-Derived Neurotrophic Factor in Slices from Rats with Spontaneous Seizures and Mossy Fiber Sprouting in the Dentate Gyrus

1999

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This study examined the acute actions of brain-derived neurotrophic factor (BDNF) in the rat dentate gyrus after seizures, because previous studies have shown that BDNF has acute effects on dentate granule cell synaptic transmission, and other studies have demonstrated that BDNF expression increases in granule cells after seizures.Pilocarpine-treated rats were studied because they not only have seizures and increased BDNF expression in granule cells, but they also have reorganization of granule cell "mossy fiber" axons. This reorganization, referred to as "sprouting," involves collaterals that grow into novel areas, i.e., the inner molecular layer, where granule cell and interneuron dendrites are located. Thus, this animal model allowed us to address the effects of BDNF in the dentate gyrus after seizures, as well as the actions of BDNF on mossy fiber transmission after reorganization.In slices with sprouting, BDNF bath application enhanced responses recorded in the inner molecular layer to mossy fiber stimulation. Spontaneous bursts of granule cells occurred, and these were apparently generated at the site of the sprouted axon plexus. These effects were not accompanied by major changes in perforant path-evoked responses or paired-pulse inhibition, occurred only after prolonged (30-60 min) exposure to BDNF, and were blocked by K252a.The results suggest a preferential action of BDNF at mossy fiber synapses, even after substantial changes in the dentate gyrus network. Moreover, the results suggest that activation of trkB receptors could contribute to the hyperexcitability observed in animals with sprouting. Because human granule cells also express increased BDNF mRNA after seizures, and sprouting can occur in temporal lobe epileptics, the results may have implications for understanding temporal lobe epilepsy.Key words: neurotrophin; growth factor; hippocampus; epilepsy; glutamate; tyrosine kinase BDNF is widely recognized as a neurotrophin with an important role in normal development that has both trophic and protective effects (Hofer and Barde, 1988;Alderson et al., 1990;Knüsel et al., 1991;Spina et al., 1992;Yan et al., 1992;Lindholm et al., 1993;Morse et al., 1993;Beck et al., 1994;Cheng and Mattson et al., 1994;Ghosh et al., 1994;Kokaia et al., 1994;Acheson et al., 1995;McAllister et al., 1995;L owenstein and Arsenault, 1996). More recently it has become clear that BDN F also has acute, neuromodulatory effects on synaptic transmission. L ohof et al. (1993) first demonstrated that exposure of neuromuscular cultures to BDNF led to increased EPSC s, and this was followed by reports of related effects in other systems (Le␤man et al

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“…Overall decreases in BDNF mRNA and protein have been reported for the hippocampus and several cortical areas (Phillips et al, 1991;Murray et al, 1994;Connor et al, 1997;Holsinger et al, 2000). Additionally, some authors described an association of BDNF with amyloid plaques (Ferrer et al, 1999;Murer et al, 1999), whereas others published negative results (Soontornniyomkij et al, 1999). Because the detailed analysis of cellular and molecular events in human postmortem tissue is intricate and often impossible, data on BDNF in AD have not yet been sufficiently conclusive.…”

Section: Introductionmentioning

confidence: 99%

Induction of Brain-Derived Neurotrophic Factor in Plaque-Associated Glial Cells of Aged APP23 Transgenic Mice

Burbach¹,

Hellweg²,

Haas³

et al. 2004

J. Neurosci.

116

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Brain-derived neurotrophic factor (BDNF) is a versatile neurotrophic factor that has been implicated in cell survival, cell differentiation, axonal growth, and activity-dependent synaptic plasticity. Changes in BDNF expression have also been reported during the course of several neurological disorders, including Alzheimer's disease (AD). The role of BDNF in AD, however, has remained elusive. To learn more about this neurotrophic factor, we investigated BDNF expression in brain of amyloid precursor protein overexpressing mice (APP23 transgenic mice). In situ hybridization revealed BDNF mRNA signals associated with amyloid plaques. Laser microdissection in combination with quantitative RT-PCR demonstrated a sixfold increase of BDNF mRNA in the immediate plaque vicinity, a threefold increase in a tissue ring surrounding the plaque, and control levels in interplaque areas comparable with those measured in age-matched nontransgenic mice. Double immunofluorescence localized BDNF to microglial cells and astrocytes surrounding the plaque. Cortical BDNF protein levels were quantified by ELISA demonstrating a Ͼ10-fold increase compared with age-matched controls. This upregulation of BDNF protein significantly correlated with the ␤-amyloid load in the transgenic animals. Taken together, our data demonstrate a plaque-associated upregulation of BDNF in APP23 transgenic mice and implicate this neurotrophin in the regulation of inflammatory and axonal growth processes in the plaque vicinity.

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An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer's disease

Cited by 168 publications

References 86 publications

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development

Actions of Brain-Derived Neurotrophic Factor in Slices from Rats with Spontaneous Seizures and Mossy Fiber Sprouting in the Dentate Gyrus

Induction of Brain-Derived Neurotrophic Factor in Plaque-Associated Glial Cells of Aged APP23 Transgenic Mice

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