4Cellular and Molecular Neuroscience Section, Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland 21224, and 5Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Exercise and IER/fasting exert complex integrated adaptive responses in the brain and peripheral tissues involved in energy metabolism. As described in the text, both exercise and IER enhance neuroplasticity and resistance of the brain to injury and disease. Some of the effects of exercise and IER on peripheral organs are mediated by the brain, including increased parasympathetic regulation of heart rate and increased insulin sensitivity of liver and muscle cells. In turn, peripheral tissues may respond to exercise and IER by producing factors that bolster neuronal bioenergetics and brain function. Examples include the following: mobilization of fatty acids in adipose cells and production of ketone bodies in the liver; production of muscle-derived neuroactive factors, such as irisin; and production of as yet unidentified neuroprotective “preconditioning factors” (Dezfulian et al., 2013). Suppression of local inflammation in tissues throughout the body and the nervous system likely contributes to prevention and reversal of many different chronic disease processes.
Running enhances adult hippocampal neurogenesis and the ability of a mouse to discriminate between two adjacent identical stimuli, enabling pattern separation. Coronal section through the mouse DG was immunofluorescent double-labeled for BrdU (green) and the neuronal marker NeuN (red).
Working model of the 5HT neural circuit responsible for the emotional (social aversive and exaggerated fear) and cognitive (shuttle box escape deficit) impact of uncontrollable stress in rats. Regular, moderate physical activity (6 weeks wheel running) produces adaptations in the circuit that include upregulation of 5HT1A inhibitory autoreceptors on DRN cell bodies and a downregulation in 5HT2C receptors in DRN projection sites, amygdala (AMG) and dorsal striatum (DS). Together, these changes constrain the 5HT response to uncontrollable stress and prevent neural sensitization and the expression of learned helplessness behaviors.
Alternate day fasting (ADF) increases activity levels and reduces body temperature in rats. Young adult male Sprague Dawley rats were implanted with transmitters to enable continuous recording of activity and body temperature in the home cage. After recording activity and temperature on the usual ad libitum diet (baseline), the rats were maintained on an ADF diet for 2 months. Examples of 24 h recordings of activity (A) and body temperature (B) from one rat are shown at baseline, on a feeding day and on a fasting day; food was either removed or supplied at 16:00 h, which was 2 h before the start of the dark period. Overall activity is greater in both the dark and light periods when the rats are on the ADF diet compared with baseline, and that during the fasting day there is a robust increase in activity beginning ∼2 h before feeding time. Values are mean ± SEM (n = 6 rats).