Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus.
ABSTRACT Physical activity induces adult hippocampal neurogenesis. We here show that the acute up-regulating effect of voluntary wheel running on precursor cell proliferation decreases with continued exercise, but that continued exercise reduces the age-dependent decline in adult neurogenesis. Cell proliferation peaked at 3 days of running. After 32 days of exercise this response returned to baseline. Running-induced proliferation of transiently amplifying progenitor cells led to a consecutive increase in the number of more mature cells. Increasing age reduced adult neurogenesis at 9 months to 50% of the value at 6 weeks and to 17% at the age of 2 years. At both 1 and 2 years, precursor cell divisions remained inducible by physical activity. Exercise from 3 to 9 months of age significantly reduced the age-dependent decline in cell proliferation but (presumably in the absence of additional stimuli) did not maintain net neurogenesis at levels corresponding to a younger age. We propose that physical activity might contribute to successful aging by increasing the potential for neurogenesis represented by the pool of proliferating precursor cells.
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ABSTRACT: Treatment resistance, along with its sibling partial response, remains a common phenomenon in schizophrenia, complicating the disability burden inherent in the disease. Antipsychotic medications are the mainstay of treatment, and treatment resistance has mainly been defined in terms of poor response to antipsychotic medication. At the same time, clozapine, the most effective antipsychotic, remains underutilized at the expense of exposing patients to polypharmacy. We review known causes of disability in schizophrenia, how they impact various areas of everyday functioning, and discuss potential treatment options including but not limited to pharmacological approaches aimed at maximizing treatment response and reducing treatment resistance.CNS spectrums 11/2014; 19:1-12. DOI:10.1017/S1092852914000571 · 1.30 Impact Factor
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ABSTRACT: Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low-intensity walking activity, which may be related to leisure-time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher-intensity walking activity. Segmentation of hippocampal volumes was performed using FMRIB's Software Library (FSL) and daily walking activity was assessed using a step activity monitor (SAM) on 92, non-demented, older adult participants. After controlling for age, education, body mass index (BMI), cardiovascular disease risk factors, and the Mini Mental State Exam (MMSE), we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not men. These relationships were specific to hippocampal volume, compared to the thalamus, used as a control brain region, and remained significant for low-intensity walking activity, independent of moderate- to vigorous-intensity activity and self-reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult sample. Findings suggest the importance of better understanding whether increasing non-exercise, lifestyle physical activities may produce measurable cognitive benefits and effect hippocampal volume through molecular pathways unique to those related to moderate-intensity exercise. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc.Hippocampus 12/2014; DOI:10.1002/hipo.22397 · 4.30 Impact Factor