Absence of Glia Maturation Factor Protects from Axonal Injury and Motor Behavioral Impairments after Traumatic Brain Injury
| Autor: | Ramasamy Thangavel, Duraisamy Kempuraj, Asher Khan, Klaudia Kukulka, Sudhanshu P. Raikwar, Kieran Bazley, Govindhasamy Pushpavathi Selvakumar, Donald James, Casey Burton, Shankar S. Iyer, Bret Bussinger, Smita Zaheer, Mohammad Ejaz Ahmed, Kristopher Wu, Asgar Zaheer |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Traumatic brain injury Glia maturation factor 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Neuroinflammation Neurotrophic factors Internal medicine Motor behavior medicine Cognitive decline Tyrosine hydroxylase biology business.industry Dopaminergic medicine.disease 030104 developmental biology Endocrinology nervous system biology.protein Parkinson’s disease Original Article Neurology (clinical) business 030217 neurology & neurosurgery Neurotrophin |
| Zdroj: | Experimental Neurobiology |
| ISSN: | 2093-8144 1226-2560 |
| Popis: | Traumatic brain injury (TBI) causes disability and death, accelerating the progression towards Alzheimer's disease and Parkinson's disease (PD). TBI causes serious motor and cognitive impairments, as seen in PD that arise during the period of the initial insult. However, this has been understudied relative to TBI induced neuroinflammation, motor and cognitive decline that progress towards PD. Neuronal ubiquitin-C-terminal hydrolase- L1 (UCHL1) is a thiol protease that breaks down ubiquitinated proteins and its level represents the severity of TBI. Previously, we demonstrated the molecular action of glia maturation factor (GMF); a proinflammatory protein in mediating neuroinflammation and neuronal loss. Here, we show that the weight drop method induced TBI neuropathology using behavioral tests, western blotting, and immunofluorescence techniques on sections from wild type (WT) and GMF-deficient (GMF-KO) mice. Results reveal a significant improvement in substantia nigral tyrosine hydroxylase and dopamine transporter expression with motor behavioral performance in GMF-KO mice following TBI. In addition, a significant reduction in neuroinflammation was manifested, as shown by activation of nuclear factor-kB, reduced levels of inducible nitric oxide synthase, and cyclooxygenase- 2 expressions. Likewise, neurotrophins including brain-derived neurotrophic factor and glial-derived neurotrophic factor were significantly improved in GMF-KO mice than WT 72 h post-TBI. Consistently, we found that TBI enhances GFAP and UCHL-1 expression and reduces the number of dopaminergic TH-positive neurons in WT compared to GMF-KO mice 72 h post-TBI. Interestingly, we observed a reduction of THpositive tanycytes in the median eminence of WT than GMF-KO mice. Overall, we found that absence of GMF significantly reversed these neuropathological events and improved behavioral outcome. This study provides evidence that PD-associated pathology progression can be initiated upon induction of TBI. |
| Databáze: | OpenAIRE |
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