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Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats

Bibliographic

Year of Publication:
2008
Contact PI Name:
Sandor Arancibia
Contact PI Affiliation:
INSERM Unité 710, Université de Montpellier II, Montpellier, France
Co-Authors:
M. Silhol, F. Moulière, J. Meffre, I. Höllinger, T. Maurice, L. Tapia-Arancibia
Primary Reference (PubMED ID):
Funding Source:
Region Languedoc-Roussillon Montpellier France
ECOS-Sud Action
Study Goal and Principal Findings:

We examined the potential protective effect of BDNF against β-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 Aβ1–42 and Aβ25–35. It completely reversed the toxic action induced by Aβ1–42 and partially that induced by Aβ25–35. 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, Aβ25–35 was administered into the indusium griseum or the third ventricle and several parameters were measured 7 days later to evaluate potential Aβ25–35/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 Aβ peptides.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Protein
Therapeutic Agent:
Brain-Derived Neurotrophic Factor (BDNF)
Therapeutic Target:
Tyrosine Receptor Kinase B (TrkB)
Therapeutic Notes:
Tyrosine Receptor Kinase B (TrkB) has been nominated as a potential target for AD. Nominated targets are obtained from several sources, including the National Institute on Aging's Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) consortium. Targets have been identified using computational analyses of high-dimensional genomic, proteomic and/or metabolomic data derived from human samples. See Agora link for more information.

Animal Model

Model Information:
Species:
Rat
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
Not Applicable

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest
Experiment Notes

Study Balanced for Sex: It is unclear whether in vivo studies were balanced for sex. Female rats were likely used to provide fetuses to generate neuronal cultures, while male rats were likely used in the in vivo studies.
Age of Animal: In studies using rats, typically the rat weight is reported rather than age. A male Sprague Dawley rat weighing 230-250g is between 6-8 weeks old. A female Sprague Dawley rat weighing 230-250g is between 9-11 weeks old.

Outcomes

Outcome Measured
Outcome Parameters
Histopathology
Cortical and Hippocampal Tissue Loss
Neuronal Loss
Pyknotic/Fragmented Nuclei
Biochemical
Somatostatin (SST) mRNA
Tyrosine Receptor Kinase B (TrkB) mRNA
Immunochemistry
Brain-Derived Neurotrophic Factor (BDNF)
Myelin Basic Protein
Somatostatin (SST)
Tyrosine Receptor Kinase B (TrkB)
Microscopy
Stereology
Neuronal Cell Number
Neuronal Morphology
Neuronal Loss
Cell Biology
Cell Viability
Neuroprotection-Amyloid Neurotoxicity
Pharmacokinetics
BDNF Concentration-Brain