Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons

Abstract

Background Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. Methods To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for seven weeks of exercise intervention. Results Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. Conclusions These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region.

Cognitive impairment and gene expression alterations in a rodent model of binge eating disorder

“…A positive correlation between CA3 TrkB expression and percent time spent with the novel object suggests that CA3 TrkB may be one of the neuronal factors for BEP specific contextual learning deficit. Previous studies employing unrestricted HFD-fed rodents have found that spatial learning and memory impairments are associated with decreased hippocampal Bdnf expression [41, 42, 74, 75], which differs from the increased CA3 Bdnf expression and learning impairments found in the BEP rats in our study. The increased Bdnf expression may be a consequence of the downregulated TrkB expression in the CA3 region, or vice versa, which in part is supported by one study showing the contrasting regulation of Bdnf and its receptor, TrkB in the primary neuronal cultures [76].…”

“…Similar to the hippocampus, intact BDNF-TrkB expression in the prefrontal cortex (PFC) can regulate working memory, discrimination reversal learning as well as object recognition learning [36–40]. Furthermore, effects of high fat diet on disrupting both hippocampal and cortical bdnf and trkb expression has been reported in rodent models [38, 40–42]. Hippocampus and PFC interact to synchronize contextual, spatial learning and memory retrieval with working memory, decision-making, and executive functions [43, 44].…”

Lifelong brain health is a lifelong challenge: From evolutionary principles to empirical evidence

“…In addition, BDNF promotes the differentiation of neural stem cells into neurons, and the survival, growth and synapse formation of the newly generated neurons (Marosi and Mattson, 2014). Such effects of BDNF signaling likely play important roles in the processes by which exercise and intermittent fasting enhance cognitive function (Mattson, 2012; Noble et al, 2014). Interestingly, recent findings suggest that BDNF signaling in the brainstem enhances activation of cardiovagal (cholinergic) neurons resulting in a reduction in resting heart rate (Wan et al, 2014).…”

Stop signs in hippocampal insulin signaling: the role of insulin resistance in structural, functional and behavioral deficits

“…Similarly, the pro-cognitive effects of the incretin analogs may result at least in part from the ability of these compounds to cross the BBB and activate hippocampal incretin signaling to promote cognition in patients with metabolic disorders [78;79]. Increased physical activity [57;80;81] and weight loss approaches [82-84] also restore behavioral performance in rodent models of T2DM and obesity, thereby supporting data indicating that lifestyle interventions enhance cognitive performance in patients with metabolic disorders. This includes aerobic exercise [85;86] and weight loss achieved through bariatric surgical procedures [87•].…”