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BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat

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Abstract

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.

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Acknowledgments

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, grant. no. ON 173056. We wish to express our gratitude to Dr. Olivera Nesic–Taylor from the University of Texas Medical Branch, Galveston, TX, for her generous gift of antibodies.

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Authors and Affiliations

  1. Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060, Belgrade, Serbia

    Milka Perovic, Vesna Tesic, Aleksandra Mladenovic Djordjevic, Kosara Smiljanic, Natasa Loncarevic-Vasiljkovic, Sabera Ruzdijic & Selma Kanazir

  2. Laboratory of Molecular Neurobiology, Department of Neurobiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 11060, Belgrade, Serbia

    Selma Kanazir

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  1. Milka Perovic
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  2. Vesna Tesic
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Correspondence to Selma Kanazir.

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ESM 1

Online Resource 1 Expression of exon I-, II-, III-, IV- and VI-containing BDNF transcripts, total BDNF and total NGF during aging. Semiquantitive RT-PCR analysis was used to determine the levels of specific mRNAs in cortex and hippocampus of 6-, 12-, 18- and 24-month-old rats. All RT-PCR reactions were performed in triplicate and at least two independent RT reactions. PCR products were resolved in a 2 % agarose gel and visualized by staining with ethidium bromide. Multi-Analyst/PC Software Image Analysis System (Bio-Rad Gel Doc 1000) was used for densitometry analysis (JPEG 21 kb)

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ESM 2

Online Resource 2 Aging did not induce neurodegeneration even when pAkt was decreased in the hippocampus. Representative photomicrographs of the cingulate/retrosplenial cortex (A) and dorsal hippocampus (B) in 24-month-old rats following Fluoro-Jade B staining of brain sections. Scattered FJB-positive neurons with smaller cell bodies and short processes are present in the same brain areas of (+)MK-801-treated animals which served as a positive control (C,D). Scale bar =50 μm (JPEG 68 kb)

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Perovic, M., Tesic, V., Mladenovic Djordjevic, A. et al. BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. AGE 35, 2057–2070 (2013). https://doi.org/10.1007/s11357-012-9495-6

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