Exercise improves cognition and hippocampal plasticity in <i>APOE</i> ɛ4 mice

Nichol, Kathryn; Deeny, Sean P.; Seif, Joseph B.; Camaclang, Kevin; Cotman, Carl W.

doi:10.1016/j.jalz.2009.02.006

Cited by 183 publications

(129 citation statements)

References 45 publications

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“…Many studies have supported the long-term benefits of exercise in humans, even in Alzheimer's and Parkinson's patients Xu et al 2010;Erickson et al 2012;Mayeux and Stern 2012;Fisher et al 2013;Intlekofer and Cotman 2013;Winchester et al 2013). Animal studies have also shown convincingly that exercise is protective in experimental models of neurodegeneration (for some examples, see Adlard et al 2005;Nichol et al 2009;Pothakos et al 2009;Zigmond et al 2009;Gerecke et al 2010;Vuckovic et al 2010;Intlekofer and Cotman 2013;Souza et al 2013). The studies on the benefits of long term exercise, dietary phytochemicals such as nicotine and caffeine, and moderate alcohol consumption all suggest that chronic adaptation to stress may be achievable in humans.…”

Section: Adaptation and Sensitization To Proteotoxic Stressmentioning

confidence: 99%

Adaptation and Sensitization to Proteotoxic Stress

Leak

2013

Dose-Response

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ᮀ Although severe stress can elicit toxicity, mild stress often elicits adaptations. Here we review the literature on stress-induced adaptations versus stress sensitization in models of neurodegenerative diseases. We also describe our recent findings that chronic proteotoxic stress can elicit adaptations if the dose is low but that high-dose proteotoxic stress sensitizes cells to subsequent challenges. In these experiments, long-term, low-dose proteasome inhibition elicited protection in a superoxide dismutase-dependent manner. In contrast, acute, high-dose proteotoxic stress sensitized cells to subsequent proteotoxic challenges by eliciting catastrophic loss of glutathione. However, even in the latter model of synergistic toxicity, several defensive proteins were upregulated by severe proteotoxicity. This led us to wonder whether high-dose proteotoxic stress can elicit protection against subsequent challenges in astrocytes, a cell type well known for their resilience. In support of this new hypothesis, we found that the astrocytes that survived severe proteotoxicity became harder to kill. The adaptive mechanism was glutathione dependent. If these findings can be generalized to the human brain, similar endogenous adaptations may help explain why neurodegenerative diseases are so delayed in appearance and so slow to progress. In contrast, sensitization to severe stress may explain why defenses eventually collapse in vulnerable neurons.

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Section: Adaptation and Sensitization To Proteotoxic Stressmentioning

confidence: 99%

Adaptation and Sensitization to Proteotoxic Stress

Leak

2013

Dose-Response

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“…BDNF and TrkB are highly expressed in the hippocampus. Many studies have reported that exercise increases hippocampal BDNF expression (47, 95,227) and that these increases are associated with enhanced cognition (26,143,195). Exactly what role, if any, hippocampal BDNF plays in energy metabolism is still unclear.…”

Section: Bdnf and The Central Regulation Of Energy Metabolismmentioning

confidence: 99%

The lighter side of BDNF

Noble

Billington

Kotz³

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

226

168

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Brain-derived neurotrophic factor (BDNF) mediates energy metabolism and feeding behavior. As a neurotrophin, BDNF promotes neuronal differentiation, survival during early development, adult neurogenesis, and neural plasticity; thus, there is the potential that BDNF could modify circuits important to eating behavior and energy expenditure. The possibility that "faulty" circuits could be remodeled by BDNF is an exciting concept for new therapies for obesity and eating disorders. In the hypothalamus, BDNF and its receptor, tropomyosin-related kinase B (TrkB), are extensively expressed in areas associated with feeding and metabolism. Hypothalamic BDNF and TrkB appear to inhibit food intake and increase energy expenditure, leading to negative energy balance. In the hippocampus, the involvement of BDNF in neural plasticity and neurogenesis is important to learning and memory, but less is known about how BDNF participates in energy homeostasis. We review current research about BDNF in specific brain locations related to energy balance, environmental, and behavioral influences on BDNF expression and the possibility that BDNF may influence energy homeostasis via its role in neurogenesis and neural plasticity. food intake; body weight; ventromedial hypothalamus; paraventricular nucleus; brain-derived neurotrophic factor BRAIN-DERIVED NEUROTROPHIC factor (BDNF) is a member of the neurotrophin family of growth factors (151), along with nerve growth factor (152), and neurotrophin (NT) 3 (67, 163), NT 4/5 (28), and NT 6 (88). Neurotrophins are synthesized as 32-35-kDa pro-isoforms, which are later cleaved to mature forms that dimerize after translation and then act as receptor ligands (136). Whereas the precursor forms of other neurotrophins are constitutively secreted, the 32-kDa pro-BDNF is packaged into vesicles of a regulated pathway and is secreted in an activitydependent manner (87). Pro-BDNF may be secreted as is (48), cleaved by the extracellular protease plasmin (202), or interact with the pan-neurotrophin receptor p75 NTR and other receptors that cause an independent biological effect (244). Alternatively, pro-BDNF is processed to the mature form intracellularly by furin or proconvertases, where it forms C-terminal dimers (212, 226).Mature BDNF is considered the biologically active form, which has a high affinity for the tropomyosin-related kinase B (TrkB) receptor (130). Both BDNF and TrkB are present in presynaptic axon terminals and postsynaptic dendritic compartments of neurons, and they are capable of bidirectional release and activity [for review, see Tyler et al. (259)]. Typical of the neurotrophic factors, BDNF stimulates the development and differentiation of new neurons (3, 131) and promotes long-term potentiation (LTP) (139,140,205), and neuron survival (97,105,116). BDNF is abundantly expressed throughout the developing and mature CNS and in many peripheral tissues, including muscle, liver, and adipose (42,159,182,261). Regional differences between BDNF mRNA levels and protein concentrations in the CNS a...

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“…Studies using voluntary wheel-running also reported positive effects on the BDNF tyrosine kinase B (trkB) signal transduction receptor [47,57,59,62,63]. Three studies specifically reported a positive correlation between distance run and BDNF mRNA or protein levels [60,61,65].…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

Relating motor and cognitive interventions in animals and humans

Carruthers¹,

Zampieri²,

Damiano³

2014

Translational Neuroscience

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Cognition and motor performance are essential components of human functioning. Recent research has provided evidence that these two domains are more interrelated than previously thought. This is a potentially important area of research with many questions that warrant further exploration and have practical implications to the field of neurological rehabilitation. In this review of literature we included animals and humans in healthy conditions as well as pathological conditions affecting the central nervous system. Our primary goal was to comprehensively review the relevant basic science and clinical literature on the e ects of motor interventions on cognitive function and vice versa. We found more evidence supporting positive effects of exercise on cognition than effects of cognitive training on motor function. In addition, we examined the extent to which findings from animal literature have been or can be translated to humans. We found that, with the exception of one study in monkeys, most animal studies which investigate rodents are somewhat challenging to translate to human studies, independent of the intervention employed. It is difficult to find a human parallel to exercise in rodents, because both the voluntary and forced exercise paradigms used in rodents happen in a di erent context than humans. In addition it is difficult to find an animal parallel to cognitive training in humans, because the environmental enrichment intervention cannot be considered "purely" cognitive stimulation as it also involves sensory, motor and social components. We conclude the review by suggesting avenues for future research and intervention strategies.

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Exercise improves cognition and hippocampal plasticity in APOE ɛ4 mice

Cited by 183 publications

References 45 publications

Adaptation and Sensitization to Proteotoxic Stress

Adaptation and Sensitization to Proteotoxic Stress

The lighter side of BDNF

Relating motor and cognitive interventions in animals and humans

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