Alpha-synuclein as a pathological link between chronic traumatic brain injury and Parkinson's disease.

Abstract

The long-term consequences of traumatic brain injury (TBI) are closely associated with the development of histopathological deficits. Notably, TBI may predispose long-term survivors to age-related neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by a gradual degeneration of the nigrostriatal dopaminergic neurons. However, preclinical studies on the pathophysiological changes in substantia nigra (SN) after chronic TBI are lacking. In the present in vivo study, we examined the pathological link between PD-associated dopaminergic neuronal loss and chronic TBI. Sixty days post-TBI, rats were euthanized and brain tissues harvested. Immunostaining was performed using tyrosine hydroxylase (TH), an enzyme required for the synthesis of dopamine in neurons, α-synuclein, a presynaptic protein that plays a role in synaptic vesicle recycling, and major histocompatibility complex II (MHCII), a protein found in antigen presenting cells such as inflammatory microglia cells, all key players in PD pathology. Unbiased stereology analyses revealed significant decrease of TH-positive expression in the surviving dopaminergic neurons of the SN pars compacta (SNpc) relative to sham control. In parallel, increased α-synuclein accumulation was detected in the ipsilateral SN compared to the contralateral SN in TBI animals or sham control. In addition, exacerbation of MHCII+ cells was recognized in the SN and cerebral peduncle ipsilateral to injury relative to contralateral side and sham control. These results suggest α-synuclein as a pathological link between chronic effects of TBI and PD symptoms as evidenced by significant overexpression and abnormal accumulation of α-synuclein in inflammation-infiltrated SN of rats exposed to chronic TBI.

• Authors: Sandra A Acosta, Naoki Tajiri, Ike de la Pena, Marina Bastawrous, Paul R Sanberg, Yuji Kaneko, Cesar V Borlongan
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 230 Issue 5 Pg. 1024-32 (May 2015) ISSN: 1097-4652 [Electronic] United States
• PMID: 25251017 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Chemical References

• Histocompatibility Antigens Class II
• alpha-Synuclein
• Tyrosine 3-Monooxygenase

Topics

• Animals
• Brain Injuries (metabolism, pathology)
• Cerebral Peduncle (metabolism, pathology)
• Chronic Disease
• Dopaminergic Neurons (metabolism, pathology)
• Down-Regulation
• Histocompatibility Antigens Class II (metabolism)
• Microglia (metabolism, pathology)
• Models, Biological
• Parkinson Disease (metabolism, pathology)
• Pars Compacta (metabolism, pathology)
• Rats, Sprague-Dawley
• Tyrosine 3-Monooxygenase (metabolism)
• Up-Regulation
• alpha-Synuclein (metabolism)