Objective: This study aimed to determine whether repetitive mild traumatic brain injury exacerbates Parkinsonian neurodegeneration and promotes alpha synuclein pathology in an experimental model.
Background: Traumatic brain injury is increasingly recognized as a significant risk factor for Parkinson’s disease. Repetitive mild brain injury may initiate progressive neurodegenerative processes, yet the mechanisms linking trauma to dopaminergic neuronal loss and alpha synuclein pathology remain poorly understood. Elucidating these interactions is critical for understanding trauma-associated Parkinsonism.
Method: Adult mice were subjected to repetitive mild traumatic brain injury followed by MPTP administration to establish a trauma-associated Parkinsonian model. Motor coordination and neuromuscular strength were evaluated using validated behavioral assays. Dopaminergic neuronal integrity and alpha synuclein pathology were assessed through histological and biochemical analyses. In addition, markers related to intracellular protein clearance pathways were examined to evaluate alterations in proteostasis. Data were analyzed using appropriate statistical methods.
Results: Animals exposed to combined injury demonstrated significantly greater motor impairment compared with single-insult groups. This functional decline was accompanied by pronounced dopaminergic neuronal loss within the substantia nigra pars compacta. Notably, enhanced alpha synuclein accumulation together with alterations in its cellular processing suggested trauma-associated dysregulation of synuclein homeostasis. Changes in markers of intracellular protein clearance pathways further indicated impaired proteostasis and reduced aggregate handling capacity in the combined injury condition.
Conclusion: Repetitive traumatic brain injury accelerates Parkinsonian neurodegeneration by disrupting alpha synuclein homeostasis and proteostasis mechanisms. These findings support the concept of trauma-primed Parkinsonism, in which prior brain injury increases vulnerability to progressive synucleinopathy and dopaminergic degeneration.
To cite this abstract in AMA style:
A. Singh, R. Gupta, S. Singh, N. Gupta. Traumatic Brain Injury Exacerbates Parkinsonian Neurodegeneration Through Alpha Synuclein Dysregulation [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/traumatic-brain-injury-exacerbates-parkinsonian-neurodegeneration-through-alpha-synuclein-dysregulation/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/traumatic-brain-injury-exacerbates-parkinsonian-neurodegeneration-through-alpha-synuclein-dysregulation/