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BACKGROUND: The effects of collagen-induced arthritis (CIA), a model of systemic inflammation, on brain regional molecular markers associated with neurological disorders are uncertain. OBJECTIVE: This study investigated the brain regional molecular changes in markers associated with inflammation and neuronal dysfunction in a CIA model. METHODS: Fourteen male Sprague Dawley rats were divided into control (n = 5) or CIA (n = 9) groups. 10 weeks after CIA induction, brain tissue was collected. Brain regional mRNA expression of inflammatory markers (IL-1ß and IL-6), apoptotic markers (BAX and Bcl2) and neurotrophic factors (BDNF, CREB and TrkB) was determined. Monoamine distribution and abundance in different brain regions were determine by mass spectrometry imaging (MSI). RESULTS: Neuroinflammation was confirmed in the CIA group by increased IL-ß mRNA expression, concurrent with an increased BAX/Bcl2 ratio. The mRNA expression of CREB was increased in the midbrain and hippocampus while BDNF was increased and TrkB was decreased across all brain regions in CIA compared to control animals. Serotonin was decreased in the midbrain and hippocampus while dopamine was decreased in the striatum of CIA rats, compared to controls. CONCLUSION: CIA resulted in neuroinflammation concurrent with an apoptotic state and aberrant expression of neurotrophic factors and monoamines in the brain, suggestive of neurodegeneration.
RESUMEN
OBJECTIVE: Estrogen deficiency is associated with left ventricular (LV) dysfunction in postmenopausal women and ovariectomized rats. Whether the relationship between estrogen deficiency and LV dysfunction is independent of cardiovascular disease (CVD) risk factors remains uncertain. This study assessed the effects of short-term and long-term estrogen deficiency on cardiac structure and function using conventional and speckle tracking echocardiography, independent of traditional CVD risk factors. METHODS: Female Sprague-Dawley rats were divided into short-term (6 wks) ovariectomized (nâ=â9), short-term sham-operated (nâ=â10), long-term (6 mo) ovariectomized (nâ=â8), and long-term sham-operated (nâ=â9) groups. Cardiac geometry, systolic and diastolic function, and myocardial deformation and motion were measured using echocardiography. RESULTS: Ovariectomy had no effect on conventional echocardiography measures of cardiac structure or function. Compared with short-term, long-term groups had reduced LV internal diameter (false discovery rate [FDR] adjusted Pâ=â0.05) and impaired relaxation (e'; FDR adjusted Pâ=â0.0005) independent of body mass and blood pressure (BP). Global longitudinal strain was impaired in ovariectomized compared with sham-operated rats (FDR adjusted Pâ=â0.05), but not after adjusting for body mass and BP (FDR adjusted Pâ=â0.16). Global longitudinal strain (FDR adjusted Pâ=â0.05), strain rate (FDR adjusted Pâ=â0.002), and velocity (FDR adjusted Pâ=â0.04) were impaired in long-term compared with short-term groups. Global longitudinal strain rate remained impaired after adjustments for body mass and BP (FDR adjusted Pâ=â0.02). CONCLUSIONS: Estrogen deficiency does not independently cause cardiac remodeling, LV dysfunction, or impaired myocardial deformation. Traditional CVD risk factors accompanying estrogen deficiency may account for cardiac remodeling and dysfunction observed in postmenopausal women.