Post-translational modifications of α-synuclein contribute to neurodegeneration in the colon of elderly individuals.
Synucleinopathies and abnormalities in the nerves of the enteric nervous system are hypothesized to be involved in age-associated motility disorders. The aim of the present study was to investigate the expression of various antigens, including α‑synuclein (Syn) and its post‑translational modified forms, in the human colon at various ages. In addition, the study aimed to correlate the expression of Syn with neurodegeneration. Immunohistochemistry was used to detect the expression of neurofilament (NF), Syn, as well as its nitrated (N) form in the healthy colonic tissue of 12 young (34.08±5.12 years), 10 middle‑aged (51.80±3.52 years), and 11 elderly (75.82±7.70 years) individuals. To the best of our knowledge, the current study is the first to demonstrate the presence of N‑Syn in the colonic tissue. N‑Syn was identified in the upper layer of the mucosa and submucosa layer. Furthermore, Syn (wild‑type) was present in the mucosa and submucosa. The number of NF‑positive neurons in the submucosal layer declined significantly with age (P<0.01). In addition, Syn and N‑Syn significantly increased during aging (P<0.01). Furthermore, a negative correlation was identified between neuron number and synucleinopathies, indicating the abnormal accumulation of both wild-type Syn and N‑Syn in the mucosa, submucosa, muscle layer and myenteric plexus. The present study demonstrates that the Syn pathology may be linked to colic neuronal degeneration during normal aging, and this link may cause functional deficits.
Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Qi
Q
Xuan
Department of Internal Medicine, Beijing Moslem Hospital, Beijing 100054, P.R. China.
Yu-Xian
YX
Zhang
Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Dian-Gang
DG
Liu
Department of Neurobiology, Institute of Geriatrics of Beijing, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, P.R. China.
Piu
P
Chan
Department of Neurobiology, Institute of Geriatrics of Beijing, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, P.R. China.
Sheng-Li
SL
Xu
Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
Ye-Qing
YQ
Cui
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000294:innervation* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009197:Myenteric Plexus / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D013368:Submucous Plexus / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein