Age-related changes in brain-derived neurotrophic factor and tyrosine kinase receptor isoforms in the hippocampus and hypothalamus in male rats.
A large amount of aging individuals show diminished cognitive and endocrine capabilities. The main brain areas involved in these changes are the hippocampus and hypothalamus, two regions possessing high plasticity and implicated in cognitive and endocrine functions, respectively. Among neurotrophins (considered as genuine molecular mediators of synaptic plasticity), brain-derived neurotrophic factor (BDNF) exhibits in adult rats, the highest concentrations in the hippocampus and hypothalamus. Most of neuronal effects of BDNF are mediated through high-affinity cell surface BDNF tyrosine kinase receptors (TrkB). Different TrkB isoforms are issued by alternative splicing of mRNA encoding for TrkB (trkB mRNA) generating at least three different TrkB receptors with different signaling capabilities. The goal of this study was to examine simultaneously the expression (mRNAs and proteins) of BDNF and its three specific receptors, in the hippocampus and hypothalamus throughout lifespan in rats. We observed that BDNF essentially increased during the first 2 postnatal weeks in the hippocampus and hypothalamus, with no close correlation to its mRNA levels. In these regions, mRNA encoding for BDNF full-length catalytic receptor (trkB.FL mRNA) showed no important changes throughout life but of the mRNA truncated forms of TrkB receptors (trkB.T1 mRNA and trkB.T2 mRNA) trkB.T1 mRNA strongly increased after birth, then remaining stable during aging. trkB.T2 mRNA gradually decreased from 1 postnatal week becoming undetectable in the hippocampus in old-rats. Proteins issued from these mRNAs showed substantial quantitative modifications with aging. From 2 months old, the BDNF full-length catalytic receptor (TrkB.FL) gradually and significantly decreased in the hippocampus and the hypothalamus. Of the truncated forms of TrkB receptors (TrkB.T1 and TrkB.T2) TrkB.T1, which is essentially localized in glial cells, significantly increased from the first postnatal week in the hippocampus and in the hypothalamus, remaining stable during aging but reduced in old rats. TrkB.T2 which similarly to TrkB.FL has a neuronal localization also gradually decreased in the hippocampus and in the hypothalamus throughout lifespan. These reductions were significant at 21 and 30 days old, respectively. All the changes reported here could contribute to the reduced plasticity of these regions observed in old rats.
Silhol
M
M
Laboratory of Cerebral Plasticity, FRE 2693 CNRS, University of Montpellier 2, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
Bonnichon
V
V
Rage
F
F
Tapia-Arancibia
L
L
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D020033:Protein Isoforms; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D020813:Receptor, trkB