PMID- 23255148 OWN - NLM STAT- MEDLINE DCOM- 20140619 LR - 20240104 IS - 1574-4647 (Electronic) IS - 0161-9152 (Print) IS - 0161-9152 (Linking) VI - 35 IP - 6 DP - 2013 Dec TI - BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. PG - 2057-70 LID - 10.1007/s11357-012-9495-6 [doi] AB - Neurotrophins are established molecular mediators of neuronal plasticity in the adult brain. We analyzed the impact of aging on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein isoforms, their receptors, and on the expression patterns of multiple 5' exon-specific BDNF transcripts in the rat cortex and hippocampus throughout the life span of the rat (6, 12, 18, and 24 months of age). ProNGF was increased during aging in both structures. Mature NGF gradually decreased in the cortex, and, in 24-month-old animals, it was 30% lower than that in adult 6-month-old rats. The BDNF expression did not change during aging, while proBDNF accumulated in the hippocampus of aged rats. Hippocampal total BDNF mRNA was lower in 12-month-old animals, mostly as a result of a decrease of BDNF transcripts 1 and 2. In contrast to the region-specific regulation of specific exon-containing BDNF mRNAs in adult animals, the same BDNF RNA isoforms (containing exons III, IV, or VI) were present in both brain structures of aged animals. Deficits in neurotrophin signaling were supported by the observed decrease in Trk receptor expression which was accompanied by lower levels of the two main downstream effector kinases, pAkt and protein kinase C. The proteolytic processing of p75NTR observed in 12-month-old rats points to an additional regulatory mechanism in early aging. The changes described herein could contribute to reduced brain plasticity underlying the age-dependent decline in cognitive function. FAU - Perovic, Milka AU - Perovic M AD - Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060, Belgrade, Serbia. FAU - Tesic, Vesna AU - Tesic V FAU - Mladenovic Djordjevic, Aleksandra AU - Mladenovic Djordjevic A FAU - Smiljanic, Kosara AU - Smiljanic K FAU - Loncarevic-Vasiljkovic, Natasa AU - Loncarevic-Vasiljkovic N FAU - Ruzdijic, Sabera AU - Ruzdijic S FAU - Kanazir, Selma AU - Kanazir S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121221 PL - Netherlands TA - Age (Dordr) JT - Age (Dordrecht, Netherlands) JID - 101250497 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Protein Precursors) RN - 0 (RNA, Messenger) RN - 0 (brain-derived neurotrophic factor precursor) RN - 0 (pro-nerve growth factor, rat) SB - IM MH - Aging/*genetics/metabolism MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/biosynthesis/*genetics MH - Cerebral Cortex/*growth & development/metabolism MH - *Gene Expression Regulation, Developmental MH - Hippocampus/*growth & development/metabolism MH - Immunohistochemistry MH - Nerve Growth Factors/biosynthesis/*genetics MH - Protein Precursors/biosynthesis/*genetics MH - RNA, Messenger/genetics MH - Rats MH - Rats, Wistar MH - Real-Time Polymerase Chain Reaction MH - Transcription, Genetic PMC - PMC3824987 EDAT- 2012/12/21 06:00 MHDA- 2014/06/20 06:00 PMCR- 2014/12/01 CRDT- 2012/12/21 06:00 PHST- 2012/06/07 00:00 [received] PHST- 2012/12/05 00:00 [accepted] PHST- 2012/12/21 06:00 [entrez] PHST- 2012/12/21 06:00 [pubmed] PHST- 2014/06/20 06:00 [medline] PHST- 2014/12/01 00:00 [pmc-release] AID - 9495 [pii] AID - 10.1007/s11357-012-9495-6 [doi] PST - ppublish SO - Age (Dordr). 2013 Dec;35(6):2057-70. doi: 10.1007/s11357-012-9495-6. Epub 2012 Dec 21.