Docosahexaenoic Acid Reduces ER Stress and Abnormal Protein Accumulation and Improves Neuronal Function Following Traumatic Brain Injury
| Autor: | Gulnaz Begum, C. E. Dixon, Hong Q. Yan, L. Li, A. Singh, Dandan Sun |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Docosahexaenoic Acids Traumatic brain injury tau Proteins Rats Sprague-Dawley Amyloid beta-Protein Precursor chemistry.chemical_compound Ubiquitin Internal medicine medicine Amyloid precursor protein Animals Inositol Neurons biology Kinase General Neuroscience Endoplasmic reticulum Articles Endoplasmic Reticulum Stress medicine.disease Frontal Lobe Rats nervous system diseases Endocrinology nervous system chemistry Docosahexaenoic acid Brain Injuries Unfolded protein response biology.protein Neuroscience |
| Zdroj: | The Journal of Neuroscience. 34:3743-3755 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2872-13.2014 |
| Popis: | In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3–21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2α, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3–21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits. |
| Databáze: | OpenAIRE |
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