Browsing by Subject "Cognitive deficits"
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Item Effect of Short-Term Alpha Lipoic Acid Supplementation on Age Related Cognitive and Motor Deficits(2001-08-01) Shetty, Ritu A.; Forster, Michael J.; Dillon, Glenn H.; Das, HridayRitu A. Shetty. Effect of short-term antioxidant supplementation on age related cognitive and motor deficits. Master of Science (Biomedical Sciences), August, 2001, 24 pp, 2 tables, 11 figures, 30 references. During aging there is an increase in oxidative damage and loss of brain function that may reflect and increased level of oxidative stress. Studies have suggested that the increased oxidative damage in old rodents can be reversed, relatively rapidly, by experimental interventions like caloric restrictions and antioxidants capable of lowering oxidative stress (Forster et.al., Joseph et.al., 1995). Based on those findings, it was hypothesized that age-related declines in cognitive and/or psychomotor function are the result of molecular damage associated with oxidative stress. The current study addressed the possibility a decreasing oxidative damage could be produced with the antioxidant alpha lipoic acid, in aged mice, leading to a reversal of age-related impairments of psychomotor and cognitive functions. C57BL/6 mice aged 6 or 23 months were gavaged daily with 100mg/kg alpha-lipoic acid or the vehicle (0.9% saline; 2% methylcellulose). After 3 weeks of treatment, the animals were subjected to a battery of behavioral tests for motor and cognitive functions. Following the behavioral tests the animals were sacrificed brains were dissected and frozen for analysis of carbonyl concentration. The results showed significant age-related deficits in spatial learning, accuracy for spatial memory, recent memory, and psychomotor performance. None of these age-related deficits was reversed following the treatment with alpha lipoic acid. There was no reduction in carbonyl concentration with alpha lipoic acid supplementation. Thus we concluded that alpha lipoic acid supplementation had neither beneficial nor detrimental effects in reducing oxidative damage in brain or in reversal the age-related decline in function.Item THE EFFECT OF LS-1-137, A NOVEL PHENYLACETAMIDE SIGMA 1 RECEPTOR SELECTIVE AGONIST ON SCOPOLAMINE-DEPENDENT COGNITIVE DEFICIT IN C57BL/6J MICE.(2014-03) Malik, Maninder; Rangel-Barajas, Claudia; Griffin, Suzy; Sumien, Nathalie; Singh, Meharvan; Maurice, Tangui; Mach, Robert; Luedtke, Robert R.Cognitive deficits are observed in aged population and in patients with Alzheimer’s Disease, Parkinson’s Disease, traumatic brain injury and stroke. Cognitive deficits often involve alterations in brain signaling. Currently available therapeutic drugs provide only symptomatic relief and generally become ineffective as disease progresses. Therefore, novel therapeutic agents are needed to retard and/or arrest the progressive loss of memory forming cells. Scopolamine-induced memory impairment model provides a relatively rapid and reversible screening paradigm for cognition enhancement drug discovery. In this study, mice were administered scopolamine and were used to evaluate the ability of LS-1-137, a novel drug, to improve the cognitive deficits. Our study results indicate that LS-1-137 may represent a novel therapeutic agent for the treatment of age and disease related cognitive deficits. Purpose (a): Cognitive deficits are observed in patients with Alzheimer’s Disease, Parkinson’s Disease, traumatic brain injury and stroke. These deficits often involve alterations in cholinergic signaling. Currently available therapeutic drugs provide only symptomatic relief and generally become ineffective as a neurodegenerative disorder progresses. Therefore, novel therapeutic agents are needed to retard and/or arrest the progressive loss of memory forming cells. Methods (b): A filtration-binding assay was used to characterize the binding properties of a novel sigma compound at D2-like dopamine receptors, muscarinic receptors and at sigma receptors. Co-immunoprecipitation assay was used for the quantification of Sigma 1 receptor-binding immunoglobulin protein (BiP) complex formation. LS-1-137 mediated brain-derived neurotrophic factor (BDNF) release was analyzed using enzyme-linked immunosorbent assay (ELISA). In this study, male C57BL/6J mice injected with scopolamine were used as experimental model to evaluate the in vivo cognitive properties of the test drug. The neuroprotective properties were evaluated using water maze and active avoidance test. Results (c): LS-1-137 binds with high affinity (Ki = 3.2 nM) at sigma 1 receptors and is 80-fold selective for sigma 1 compared to sigma 2 receptor. LS-1-137 binds with low affinity at D2-like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1-137 was found to partially reverse the learning and memory deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS-1-137 treatment modulates sigma 1 receptor- BiP complex formation and also triggers the release of BDNF from rat astrocytes. Conclusions (d): LS-1-137 may represent a novel candidate cognitive enhancer for the treatment of cholinergic muscarinic-dependent cognitive deficits.