Conjugated linoleic acid prevents age-dependent neurodegeneration in a mouse model of neuropsychiatric lupus via the activation of an adaptive response
| Autor: | Floriana Boscaino, Ennio Cocca, Luisa Cigliano, Maria Stefania Spagnuolo, Francesco Maurano, Ida Ferrandino, Paolo Bergamo, Antonio Monaco, Diomira Luongo, Mauro Rossi |
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| Přispěvatelé: | Monaco, Antonio, Ferrandino, Ida, Boscaino, Floriana, Cocca, Ennio, Cigliano, Luisa, Maurano, Francesco, Luongo, Diomira, Spagnuolo, Maria Stefania, Rossi, Mauro, Bergamo, Paolo |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine autophagy medicine.medical_specialty Conjugated linoleic acid Administration Oral QD415-436 urologic and male genital diseases medicine.disease_cause Biochemistry Neuroprotection Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology immune system diseases Internal medicine medicine Animals Lupus Erythematosus Systemic Linoleic Acids Conjugated skin and connective tissue diseases Research Articles Mice Inbred BALB C Systemic lupus erythematosus Hyperactivation business.industry Neurodegeneration Autophagy Age Factors Nrf2 pathway astrogliosi Cell Biology medicine.disease Astrogliosis Disease Models Animal Oxidative Stress 030104 developmental biology chemistry astrogliosis Nerve Degeneration Immunology Female neuroprotection business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Journal of Lipid Research, Vol 59, Iss 1, Pp 48-57 (2018) |
| ISSN: | 0022-2275 |
| Popis: | Oxidative stress is a key mediator of autoimmune/neurodegenerative disorders. The antioxidant/anti-inflammatory effect of a synthetic conjugated linoleic acid (CLA) mixture in MRL/MpJ-Fas lpr mice (MRL/lpr), an animal model of neuropsychiatric lupus, was previously associated with the improvement of nuclear factor-E2-related factor 2 (Nrf2) defenses in the spleen and liver. However, little is known about the neuroprotective ability of a CLA mixture. This study investigated the age-dependent progression of oxidative stress and the hyperactivation of redox-sensitive compensatory pathways (macroautophagy, Nrf2) in old/diseased MRL/lpr mice brains and examines the effect produced by dietary CLA supplementation. Disrupted redox homeostasis was evidenced in the blood, liver, and brain of 21- to 22-week-old MRL/lpr (Old) mice compared with 8- to 10-week-old MRL/lpr (Young) animals. This alteration was associated with significant hyperactivation of compensatory mechanisms (macroautophagy, Nrf2, and astrocyte activation) in the brains of Old mice. Five-week daily supplementation with CLA (650 mg/kg-1 body weight) of 16-week-old (CLA+Old) mice diminished all the pathological hallmarks at a level comparable to Young mice or healthy controls (BALB/c). Such data demonstrated that MRL/lpr mice can serve as a valuable model for the evaluation of the effectiveness of neuroprotective drugs. Notably, the preventive effect provided by CLA supplementation against age-associated neuronal damage and hyperactivation of compensatory mechanisms suggests that the activation of an adaptive response is at least in part accountable for its neuroprotective ability. |
| Databáze: | OpenAIRE |
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