Physical Therapy

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

Physical activity—a lifestyle factor that is associated with immune function, neuroprotection, and energy metabolism—modulates the cellular and molecular processes in the brain that are vital for emotional and cognitive health, collective mechanisms that can go awry in depression. Physical activity optimizes the stress response, neurotransmitter level and function (e.g., serotonergic, noradrenergic, dopaminergic, and glutamatergic), myokine production (e.g., interleukin-6), transcription factor levels and correlates [e.g., peroxisome proliferator-activated receptor C coactivator-1α [PGC-1α], mitochondrial density, nitric oxide pathway activity, Ca2+ signaling, reactive oxygen specie production, and AMP-activated protein kinase [AMPK] activity], kynurenine metabolites, glucose regulation, astrocytic health, and growth factors (e.g., brain-derived neurotrophic factor). Dysregulation of these interrelated processes can effectuate depression, a chronic mental illness that affects millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility in understanding chronic depression, a need remains to better understand the interrelated mechanisms that contribute to immune dysfunction and the means by which various therapeutics mitigate them. Fortunately, convergent evidence suggests that physical activity improves emotional and cognitive function in persons with depression, particularly in those with comorbid inflammation. Accordingly, the aims of this review are to (1) underscore the link between inflammatory correlates and depression, (2) explicate immuno-neuroendocrine foundations, (3) elucidate evidence of neurotransmitter and cytokine crosstalk in depressive pathobiology, (4) determine the immunomodulatory effects of physical activity in depression, (5) examine protocols used to effectuate the positive effects of physical activity in depression, and (6) highlight implications for clinicians and scientists. It is our contention that a deeper understanding of the mechanisms by which inflammation contributes to the pathobiology of depression will translate to novel and more effective treatments, particularly by identifying relevant patient populations that can benefit from immune-based therapies within the context of personalized medicine.

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors—including physical activity, cognitive engagement, and diet—are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Mood disorders (MDs) are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA) has shown clear and consistent promise. Accordingly, the aims of this review are to (1) explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2) explore the putative mechanisms by which PA mitigates these features; (3) review protocols used to induce the positive effects of PA in MDs; and (4) highlight implications for clinicians and researchers.