Doublecortin and IGF-1R protein levels are reduced in spite of unchanged DNA methylation in the hippocampus of aged rats
Autor: | Katja Zappe, Nasim Sanadgol, Gert Lubec, Georg Pretsch, Roman Smidak, Jana Lubec, Harald Höger, Margit Cichna‑Markl, Volker Korz |
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Rok vydání: | 2020 |
Předmět: |
Doublecortin Domain Proteins
Male 0301 basic medicine Aging medicine.medical_specialty Doublecortin Protein Receptor Metabotropic Glutamate 5 Clinical Biochemistry Hippocampus Protein degradation Hippocampal formation Biochemistry Receptor IGF Type 1 Rats Sprague-Dawley 03 medical and health sciences Cognition Internal medicine medicine Animals Promoter Regions Genetic Spatial Memory Messenger RNA 030102 biochemistry & molecular biology biology Dentate gyrus Neuropeptides Organic Chemistry Methylation DNA Methylation Rats Doublecortin 030104 developmental biology Endocrinology DNA methylation biology.protein Microtubule-Associated Proteins |
Zdroj: | Amino Acids. 52:543-553 |
ISSN: | 1438-2199 0939-4451 |
Popis: | The aim of the current study was to investigate whether doublecortin (DCX), insulin-like growth factor receptor 1 (IGF-1R) and metabotropic glutamate receptor 5 (mGluR5) levels are indeed modified in the aging rat hippocampal individual subareas (rather than total hippocampal tissue as in previous reports) at the protein and mRNA level and whether the methylation status contributes to these changes. Since the aging population is not homogeneous in terms of spatial memory performance, we examined whether changes in DCX, IGF-1R and mGluR5 are linked to cognitive aging. Aged (22 months) male Sprague Dawley rats were trained in the hole-board, a spatial memory task, and were subdivided according to performance to aged impaired and aged unimpaired groups. Age- and memory performance-dependent changes in mRNA steady-state levels, protein levels and DNA methylation status of DCX, IGF-1R and mGluR5 were evaluated by RT-PCR, immunoblotting and bisulfite pyrosequencing. Extending previous findings, we detected decreased DCX protein and mRNA levels in dentate gyrus (DG) of aged animals. IGF-1 signaling is a key event and herein we show that mRNA levels for IGF-1R were unchanged although reduced at the protein level. This finding may simply reflect that these protein levels are regulated at the level of protein synthesis as well as protein degradation. We provide evidence that promoter methylation is not involved in regulation of mRNA and protein levels of DCX, IGF-1R and mGluR5 during aging. Moreover, there was no significant difference between aged rats with impaired and aged rats with unimpaired memory at the protein and mRNA level. Findings propose that changes in the abovementioned protein levels may not be relevant for performance in the spatial memory task used in aged rats. |
Databáze: | OpenAIRE |
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