Exendin-4 induced glucagon-like peptide-1 receptor activation reverses behavioral impairments of mild traumatic brain injury in mice
| العنوان: | Exendin-4 induced glucagon-like peptide-1 receptor activation reverses behavioral impairments of mild traumatic brain injury in mice |
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| المؤلفون: | Barry J. Hoffer, Nigel H. Greig, Lital Rachmany, Yazhou Li, Chaim G. Pick, Jonathan P. Miller, Vardit Rubovitch, David Tweedie, Harold W. Holloway |
| المصدر: | AGE. 35:1621-1636 |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Aging, medicine.medical_specialty, Elevated plus maze, Traumatic brain injury, Excitotoxicity, Incretin, medicine.disease_cause, Bioinformatics, Incretins, Neuroprotection, Glucagon-Like Peptide-1 Receptor, Article, Cell Line, Rats, Sprague-Dawley, Mice, Alzheimer Disease, Glucagon-Like Peptide 1, Memory, Internal medicine, Receptors, Glucagon, medicine, Animals, Humans, Stroke, Trauma Severity Indices, Behavior, Animal, Venoms, business.industry, Glutamate receptor, Brain, Recognition, Psychology, General Medicine, medicine.disease, Rats, Disease Models, Animal, Oxidative Stress, Neuroprotective Agents, Endocrinology, Brain Injuries, Exenatide, Geriatrics and Gerontology, Alzheimer's disease, Peptides, business |
| الوصف: | Mild traumatic brain injury (mTBI) represents a major and increasing public health concern and is both the most frequent cause of mortality and disability in young adults and a chief cause of morbidity in the elderly. Albeit mTBI patients do not show clear structural brain defects and, generally, do not require hospitalization, they frequently suffer from long-lasting cognitive, behavioral, and emotional problems. No effective pharmaceutical therapy is available, and existing treatment chiefly involves intensive care management after injury. The diffuse neural cell death evident after mTBI is considered mediated by oxidative stress and glutamate-induced excitotoxicity. Prior studies of the long-acting GLP-1 receptor agonist, exendin-4 (Ex-4), an incretin mimetic approved for type 2 diabetes mellitus treatment, demonstrated its neurotrophic/protective activity in cellular and animal models of stroke, Alzheimer’s and Parkinson’s diseases, and, consequent to commonalities in mechanisms underpinning these disorders, Ex-4 was assessed in a mouse mTBI model. In neuronal cultures in this study, Ex-4 ameliorated H2O2-induced oxidative stress and glutamate toxicity. To evaluate in vivo translation, we administered steady-state Ex-4 (3.5 pM/kg/min) or saline to control and mTBI mice over 7 days starting 48 h prior to or 1 h post-sham or mTBI (30 g weight drop under anesthesia). Ex-4 proved well-tolerated and fully ameliorated mTBI-induced deficits in novel object recognition 7 and 30 days post-trauma. Less mTBI-induced impairment was evident in Y-maze, elevated plus maze, and passive avoidance paradigms, but when impairment was apparent Ex-4 induced amelioration. Together, these results suggest that Ex-4 may act as a neurotrophic/neuroprotective drug to minimize mTBI impairment. |
| تدمد: | 1574-4647 0161-9152 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77d418dffa967e38025e0652f4c6c010Test https://doi.org/10.1007/s11357-012-9464-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....77d418dffa967e38025e0652f4c6c010 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15744647 01619152 |
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