Kirkwood E Personius1, Sara D Parker. 1. Program in Neuroscience, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA. kep7@buffalo.edu
Abstract
INTRODUCTION: Full-length tyrosine kinase B (TrkB.FL) and truncated TrkB (TrkB.t1) receptors are colocalized with acetylcholine receptors (AChRs) at the neuromuscular junction. We have recently shown that reduced TrkB expression leads to age-related alterations in AChR structure, neurotransmission failure, and muscle weakness. METHODS: We investigated whether TrkB expression is reduced in the soleus muscle during aging. RESULTS: TrkB protein expression was decreased in senescent (24-month-old) compared with 3-12-month-old mice. Loss of TrkB expression was concurrent with age-related changes in AChR morphology. Changes in mRNA levels did not correlate with protein expression, because TrkB.FL copy number was increased in the senescent soleus. No change was seen in TrkB.t1 levels. CONCLUSIONS: The results suggest that reduced TrkB expression during aging may result from reduced TrkB.FL mRNA translation or increased TrkB protein turnover. Thus, maintaining adequate TrkB signaling is a potential therapeutic tool to improve muscle function during senescence.
INTRODUCTION: Full-length tyrosine kinase B (TrkB.FL) and truncated TrkB (TrkB.t1) receptors are colocalized with acetylcholine receptors (AChRs) at the neuromuscular junction. We have recently shown that reduced TrkB expression leads to age-related alterations in AChR structure, neurotransmission failure, and muscle weakness. METHODS: We investigated whether TrkB expression is reduced in the soleus muscle during aging. RESULTS:TrkB protein expression was decreased in senescent (24-month-old) compared with 3-12-month-old mice. Loss of TrkB expression was concurrent with age-related changes in AChR morphology. Changes in mRNA levels did not correlate with protein expression, because TrkB.FL copy number was increased in the senescent soleus. No change was seen in TrkB.t1 levels. CONCLUSIONS: The results suggest that reduced TrkB expression during aging may result from reduced TrkB.FL mRNA translation or increased TrkB protein turnover. Thus, maintaining adequate TrkB signaling is a potential therapeutic tool to improve muscle function during senescence.
Authors: Sudhakar Aare; Sally Spendiff; Madhusudanarao Vuda; Daren Elkrief; Anna Perez; Qinghua Wu; Dominique Mayaki; Sabah N A Hussain; Stefan Hettwer; Russell T Hepple Journal: Skelet Muscle Date: 2016-09-01 Impact factor: 4.912
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