Exercise as an antidepressant: exploring its therapeutic potential.

The COVID-19 pandemic has increased the prevalence of depressive disorders worldwide, requiring alternative treatments beyond medication and psychotherapy. Exercise has positive effects on the brain; therefore, it has emerged as a promising therapeutic option for individuals with depression. Considerable research involving humans and animals offers compelling evidence to support the mental health benefits of physical activity or exercise mediated by the regulation of complex theoretical paradigms. However, challenges such as conducting long-term follow-up assessments and considering individual characteristics remain in human studies despite extensive efforts. While animal studies provide valuable insights into the potential benefits of exercise and its impact on outcomes related to depression and anxiety in rodents exposed to different stress paradigms, translating the findings to humans requires careful evaluation. More research is needed to establish precise exercise prescription guidelines and to better understand the complex relationship between exercise and depressive disorders. Therefore, this concise review explores the evidence supporting exercise intervention as an antidepressant treatment and its underlying mechanisms.

Effectiveness of Pilates Training on Body Composition and Isokinetic Muscular Strength in Adolescent Baseball Players.

Body composition and muscular strength are important for baseball skills and successful performance. Conditioning training programs have the potential to enhance athletic performance via physiological changes. In this single-group interventional study, we investigated the effect of 8 weeks of Pilates training (PT) on contralateral and regional body composition, and isokinetic muscular strength in knee and trunk flexion/extension in adolescent baseball players. In our results, PT increased both right- and left-sided lean mass in the trunk. Following PT, work per repetition and average power showed significant increases in the flexion and extension of the left knee only. PT significantly decreased the peak torque of the trunk flexor and increased the average power of the trunk extensor. In addition, the ratio of the trunk flexion/extension strength of peak torque showed a decreasing trend, whereas that of work and average power did not change significantly following PT. In conclusion, PT evenly improved lean mass on both the right and left sides of the body. Knee and trunk strength increased after PT. Our findings suggest that PT may be a useful strategy for enhancing athletic performance in regard to the muscular strength of adolescent baseball players.

Real-time visualization of mRNA synthesis during memory formation in live mice.

Memories are thought to be encoded in populations of neurons called memory trace or engram cells. However, little is known about the dynamics of these cells because of the difficulty in real-time monitoring of them over long periods of time in vivo. To overcome this limitation, we present a genetically encoded RNA indicator (GERI) mouse for intravital chronic imaging of endogenous Arc messenger RNA (mRNA)-a popular marker for memory trace cells. We used our GERI to identify Arc-positive neurons in real time without the delay associated with reporter protein expression in conventional approaches. We found that the Arc-positive neuronal populations rapidly turned over within 2 d in the hippocampal CA1 region, whereas ∼4% of neurons in the retrosplenial cortex consistently expressed Arc following contextual fear conditioning and repeated memory retrievals. Dual imaging of GERI and a calcium indicator in CA1 of mice navigating a virtual reality environment revealed that only the population of neurons expressing Arc during both encoding and retrieval exhibited relatively high calcium activity in a context-specific manner. This in vivo RNA-imaging approach opens the possibility of unraveling the dynamics of the neuronal population underlying various learning and memory processes.

Breathing Exercises for Improving Cognitive Function in Patients with Stroke.

Patients with stroke may experience a certain degree of cognitive decline during the period of recovery, and a considerable number of such patients have been reported to show permanent cognitive damage. Therefore, the period of recovery and rehabilitation following stroke is critical for rapid cognitive functional improvements. As dysfunctional breathing has been reported as one of the factors affecting the quality of life post stroke, a number of studies have focused on the need for improving the breathing function in these patients. Numerous breathing exercises have been reported to enhance the respiratory, pulmonary, cognitive, and psychological functions. However, scientific evidence on the underlying mechanisms by which these exercises improve cognitive function is scattered at best. Therefore, it has been difficult to establish a protocol of breathing exercises for patients with stroke. In this review, we summarize the psychological, vascular, sleep-related, and biochemical factors influencing cognition in patients and highlight the need for breathing exercises based on existing studies. Breathing exercises are expected to contribute to improvements in cognitive function in stroke based on a diverse array of supporting evidence. With relevant follow-up studies, a protocol of breathing exercises can be developed for improving the cognitive function in patients with stroke.

Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus.

The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in individuals with Parkinson's disease. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, the input circuit and cellular profile in the STN remain largely unclear. Using neuroanatomical techniques, we construct a comprehensive connectivity map of the indirect and hyperdirect pathways in the mouse STN. Our circuit- and cellular-level connectivities reveal a topographically graded organization with three types of indirect and hyperdirect pathways (external globus pallidus only, STN only, and collateral). We confirm consistent pathways into the human STN by 7 T MRI-based tractography. We identify two functional types of topographically distinct glutamatergic STN neurons (parvalbumin [PV+/-]) with synaptic connectivity from indirect and hyperdirect pathways. Glutamatergic PV+ STN neurons contribute to burst firing. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.

The Relationship between Body Composition and Physical Fitness and the Effect of Exercise According to the Level of Childhood Obesity Using the MGPA Model.

Childhood obesity can lead to adulthood obesity with adverse effects. Since body composition and physical fitness differ depending on the obesity degree, a systemic analysis could help classify that degree. We used three study designs based on the obesity degree (body mass index [BMI] as a reference) for our objectives. First, we identified the relationship between body composition and physical fitness. Second, we determined the effects of exercise on body composition and physical fitness. Third, we performed a path analysis of the impact of exercise on body composition and physical fitness, and verified those effects among the groups. In study 1, 164 10-year-old subjects were divided into four groups: 33 in the normal weight (NO), 34 in overweight (OV), 54 in obesity (OB), and 43 in the severe obesity (SOB) group. In study 2, 101 participants from study 1 who wished to participate in the exercise program were divided into four groups (same criteria). The exercise program (three times a week for 60 min, for 16 weeks) consisted of sports and reinforcement exercises of increasing intensity. Body composition was measured by body weight, percentage of body fat (%BF), muscle mass, skeletal muscle mass (SMM), and body mass index (BMI). In contrast, physical fitness was measured by muscular strength, flexibility, muscular endurance, agility, and balance. As a result, all body composition variables were higher in the SOB group than in the other groups. Physical fitness, muscular strength and balance, and agility were highest in the SOB, NO, and OV groups, respectively. Pearson's correlation revealed that muscular strength was associated with height and body weight across all groups. Agility showed a negative correlation with %BF in the NO, OB, and SOB groups. SMM was positively correlated in the OB and SOB groups. After the exercise intervention, BMI and the %BF of the SOB group were significantly reduced (p < 0.01, and p < 0.001, respectively), while SMM presented a significant increase (p < 0.001). Height also showed a significant increase in all groups (p < 0.001). Among physical fitness variables, muscular strength, flexibility, muscular endurance, and balance showed a significant increase in all groups, while a significant increase in power was observed in only the OB and SOB groups. As for the effects of the body composition on physical fitness after exercise intervention, the greatest impact was observed for balance, muscular strength and agility, and muscular endurance in NO, OV, and OB groups, respectively. In conclusion, the body composition, physical fitness relationship, and the effects of exercise intervention on them differed depending on the obesity degree. Furthermore, the results varied according to the obesity degree. Thus, our study highlights the importance of creating particular exercise programs for the effective prevention and treatment of childhood obesity considering the obesity degree.

Exercise-Induced Adrenocorticotropic Hormone Response Is Cooperatively Regulated by Hypothalamic Arginine Vasopressin and Corticotrophin-Releasing Hormone.

INTRODUCTION: Exercise becomes a stress when performed at an intensity above the lactate threshold (LT) because at that point the plasma adrenocorticotropic hormone (ACTH), a marker of stress response, increases. It is possible that the exercise-induced ACTH response is regulated at least by arginine vasopressin (AVP) and possibly by corticotropin-releasing hormone (CRH), but this remains unclear. To clarify the involvement of these factors, it is useful to intervene pharmacologically in the regulatory mechanisms, with a physiologically acceptable exercise model. METHODS: We used a special stress model of treadmill running (aerobic exercise) for male Wistar rats, which mimic the human physiological response, where plasma ACTH levels increase at just above the LT for 30 min. Animals were administered the AVP V1b receptor antagonist SSR149415 (SSR) and/or the CRH type 1 receptor antagonist CP154526 (CP) intraperitoneally before the exercise, which allowed the monitoring of exercise-induced ACTH response. Immunohistochemical evaluation of activated AVP and CRH neurons with exercise was performed for the animals' hypothalami. RESULTS: A single injection of either antagonist, SSR or CP, resulted in inhibited ACTH levels after exercise stress. Moreover, the combined injection of SSR and CP strongly suppressed ACTH secretion during treadmill running to a greater extent than each alone. The running-exercise-induced activation of both AVP and CRH neurons in the hypothalamus was also confirmed. CONCLUSION: These results lead us to hypothesize that AVP and CRH are cooperatively involved in exercise-induced ACTH response just above the LT. This may also reflect the stress response with moderate-intensity exercise in humans.

Convergence Circuit Mapping: Genetic Approaches From Structure to Function.

Understanding the complex neural circuits that underpin brain function and behavior has been a long-standing goal of neuroscience. Yet this is no small feat considering the interconnectedness of neurons and other cell types, both within and across brain regions. In this review, we describe recent advances in mouse molecular genetic engineering that can be used to integrate information on brain activity and structure at regional, cellular, and subcellular levels. The convergence of structural inputs can be mapped throughout the brain in a cell type-specific manner by antero- and retrograde viral systems expressing various fluorescent proteins and genetic switches. Furthermore, neural activity can be manipulated using opto- and chemo-genetic tools to interrogate the functional significance of this input convergence. Monitoring neuronal activity is obtained with precise spatiotemporal resolution using genetically encoded sensors for calcium changes and specific neurotransmitters. Combining these genetically engineered mapping tools is a compelling approach for unraveling the structural and functional brain architecture of complex behaviors and malfunctioned states of neurological disorders.

High-intensity Intermittent Training Enhances Spatial Memory and Hippocampal Neurogenesis Associated with BDNF Signaling in Rats.

High-intensity intermittent (or interval) training (HIIT) has started to gain popularity as a time-effective approach to providing beneficial effects to the brain and to peripheral organs. However, it still remains uncertain whether HIIT enhances hippocampal functions in terms of neurogenesis and spatial memory due to unconsidered HIIT protocol for rodents. Here, we established the HIIT regimen for rats with reference to human study. Adult male Wistar rats were assigned randomly to Control, moderate-intensity continuous training (MICT; 20 m/min, 30 min/day, 5 times/week), and HIIT (60 m/min, 10 30-s bouts of exercise, interspaced with 2.5 min of recovery, 5 times/week) groups. The ratios of exercise time and volume between MICT and HIIT were set as 6:1 and 2:1-4:1, respectively. After 4 weeks of training, all-out time in the incremental exercise test was prolonged for exercise training. In skeletal muscle, the plantaris citrate synthase activity significantly increased only in the HIIT group. Simultaneously, both HIIT and MICT led to enhanced spatial memory and adult hippocampal neurogenesis (AHN) as well as enhanced protein levels of hippocampal brain-derived neurotrophic factor (BDNF) signaling. Collectively, we suggest that HIIT could be a time-efficient exercise protocol that enhances hippocampal memory and neurogenesis in rats and is associated with hippocampal BDNF signaling.

Exercise training and burdock root (Arctium lappa L.) extract independently improve abdominal obesity and sex hormones in elderly women with metabolic syndrome.

The prevalence of metabolic syndrome (MS) is increasing among the elderly, and new lifestyle-based treatment strategies are warranted. We conducted a randomized, double-blind controlled trial of the effects of aquatic exercise (AE) and/or consumption of burdock root extract (BE) on body composition and serum sex hormones, i.e., testosterone, estradiol, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone-sulfate (DHEA-S) in elderly women with MS. The percentage of abdominal fat was decreased in the AE group. Waist circumference was increased in the control (CON) group, but not in the other groups. SHBG and estradiol levels were enhanced by both AE and BE and correlated with changes in fat-related body composition. DHEA-S levels only increased in the BE group, which was consistent with changes in lean body mass. Testosterone levels decreased in the CON group, which correlated with changes in lean body mass, skeletal muscle mass, body fat, and waist circumference. Our findings suggested that the combined AE/BE intervention exerted no synergistic and/or additive effects on any sex-related outcome measures in elderly women with MS.

Neuroprotective Benefits of Exercise and MitoQ on Memory Function, Mitochondrial Dynamics, Oxidative Stress, and Neuroinflammation in D-Galactose-Induced Aging Rats.

Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.

Preventive role of regular low-intensity exercise during adolescence in schizophrenia model mice with abnormal behaviors.

Schizophrenia is probably ascribed to perinatal neurodevelopmental deficits, and its onset might be affected by environmental factors. Hypofrontality with glutamatergic and dopaminergic neuronal dysfunction are known factors, but a way to mitigate abnormalities remains unfound. An early enriched environment such as a wheel running in rodents may contribute to the prevention, but its clinical applicability is very limited. From our studies, low-intensity exercise training (LET) based on physiological indices, such as lactate threshold, easily translates to humans and positively affects the brains. Hence, LET during adolescence may ameliorate abnormalities in neurodevelopment and prevent the development of schizophrenia. In the current study, LET prevented sensitization to phencyclidine (PCP) treatment, impairment of cognition, and affective behavioral abnormalities in an animal model of schizophrenia induced by prenatal PCP treatment. Further, LET increased dopamine turnover and attenuated the impairment of phosphorylation of ERK1/2 after exposure to a novel object in the prenatal PCP-treated mice. These results suggest that LET during adolescence completely improves schizophrenia-like abnormal behaviors associated with improved glutamate uptake and the dopamine-induced ERK1/2 signaling pathway in the PFC.

Possible adaptogenic effects of Momordica charantia on high-intensity training-induced alteration in the hypothalamic-pituitary-adrenal axis.

This study investigated the effects of a drink supplement containing Momordica charantia extract from bitter melon on physical fitness and levels of stress hormones during a four-week exercise training program in a hot environment. Ten male tennis players were orally administrated in a four-week (100 ml, 6 times a day), and the pre- and post-supplementation levels of different physical fitness variables and cortisol, and adrenocorticotropic hormone in plasma were measured at four time-points-before (baseline), during, and after the exercise, and on the next day of the supplementation. The findings showed that the supplementation has significant positive effects on enhancement of physical fitness parameters especially balance (d = 22.10, p = 0.013), flexibility (d = 4.83, p = 0.015), and cardiorespiratory fitness (d = 10.00, p = 0.030). Moreover, the adrenocorticotropic hormone levels were reduced during the exercise, and the cortisol levels showed the decreasing trend during and after the exercise, which was correlated with the change of cardiorespiratory fitness (r = 0.65, p<0.05). These results indicated the possible adaptogenic effects of Momordica charantia extract intake. Based on the findings, we suggest that Momordica charantia could be used as a source of adaptogenic supplement to alleviate the exercise- and environment-induced stress.

Potential Biomarkers of Peripheral and Central Fatigue in High-Intensity Trained Athletes at High-Temperature: A Pilot Study with Momordica charantia (Bitter Melon).

Among potent dietary supplements, Momordica charantia, commonly called bitter melon, has various biological effects, such as antioxidant and anti-inflammatory effects, and improves energy metabolism and fatigue recovery. However, it is unknown whether Momordica charantia extract (MCE) induces antifatigue effects during exercise training in high-temperature environments. This study aimed at investigating the efficacy of MCE by examining 10 male tennis players consuming 100 mL MCE/dose (6 times a day over 4 weeks) during the summer training season. Peripheral (ammonia and uric acid) and central (serotonin, dopamine, and prolactin) fatigue parameters were measured before and after MCE consumption; before, during, and after exercise; and the next morning. After consuming MCE supplements, ammonia levels were higher during and after exercise and recovered the next morning, whereas uric acid levels did not change at any time point. Serotonin levels were lower during exercise. Dopamine levels were higher, especially during exercise. Prolactin levels were lower at all time points, especially during and after exercise. Although high-intensity training in a hot environment causes accumulation of fatigue-related metabolites, our results indicate that 4 weeks of MCE intake positively influenced fatigue parameters, suggesting that MCE can efficiently combat fatigue.

Potential role of phytochemicals in brain plasticity: Focus on polyunsaturated fatty acids.

PURPOSE: Functional foods are thought to strongly influence the structure and function of the brain. Previous studies have reported that brain-boosting diets may enhance neuroprotective functions. Certain foods are particularly rich in nutrients like phytochemicals that are known to support brain plasticity; such foods are commonly referred to as brain foods. METHODS: In this review, we briefly explore the scientific evidence supporting the neuroprotective activity of a number of phytochemicals with a focus on phenols and polyunsaturated fatty acids such as flavonoid, olive oil, and omega-3 fatty acid. RESULTS: The aim of this study was to systematically examine the primary issues related to phytochemicals in the brain. These include (a) the brain-gut-microbiome axis; (b) the effects of phytochemicals on gut microbiome and their potential role in brain plasticity; (c) the role of polyunsaturated fatty acids in brain health; and (d) the effects of nutrition and exercise on brain function. CONCLUSION: This review provides evidence supporting the view that phytochemicals from medicinal plants play a vital role in maintaining brain plasticity by influencing the brain-gut-microbiome axis. The consumption of brain foods may have neuroprotective effects, thus protecting against neurodegenerative disorders and promoting brain health.

Interactive Improvements of Visual and Auditory Function for Enhancing Performance in Youth Soccer Players.

We analyzed the effects of a regular training program on the health- and skill-related physical fitness (PF) of talented soccer players aged < 12 years; visual reaction time (VRT) and auditory reaction time (ART) were also assessed. In this single-group interventional study, 78 talented male youth soccer players (mean age, 9.54 years) were critically selected by the Korean Educational Development Institute and underwent a 22-week training program consisting of 16 weeks of PF and basic skill training (90 min/week) and 6 weeks of intensive training (3, 150-min sessions/week). We assessed the pre- and post-training body composition, cardiovascular endurance, muscle strength and endurance, and flexibility. We also measured power, agility, coordination and speed, passing ability, VRT, and ART. All variables improved after training. Post-training VRT correlated with ART, muscle mass, power, cardiovascular endurance, 10-m dribble time, 10-m ball touch count, and 10-m successful pass count. ART only correlated with muscle mass. ART and 10-m ball-touch count influenced VRT, and VRT influenced ART. In conclusion, the training program enhanced the PF and visual- and auditory-related reactions in talented youth soccer players. This study suggests the importance of the assessed relationships, indicating that a training program that improves these parameters enhances the players' performance.

Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory.

Regular exercise and dietary supplements with antioxidants each have the potential to improve cognitive function and attenuate cognitive decline, and, in some cases, they enhance each other. Our current results reveal that low-intensity exercise (mild exercise, ME) and the natural antioxidant carotenoid astaxanthin (AX) each have equivalent beneficial effects on hippocampal neurogenesis and memory function. We found that the enhancement by ME combined with AX in potentiating hippocampus-based plasticity and cognition is mediated by leptin (LEP) made and acting in the hippocampus. In assessing the combined effects upon wild-type (WT) mice undergoing ME with or without an AX diet for four weeks, we found that, when administrated alone, ME and AX separately enhanced neurogenesis and spatial memory, and when combined they were at least additive in their effects. DNA microarray and bioinformatics analyses revealed not only the up-regulation of an antioxidant gene, ABHD3, but also that the up-regulation of LEP gene expression in the hippocampus of WT mice with ME alone is further enhanced by AX. Together, they also increased hippocampal LEP (h-LEP) protein levels and enhanced spatial memory mediated through AKT/STAT3 signaling. AX treatment also has direct action on human neuroblastoma cell lines to increase cell viability associated with increased LEP expression. In LEP-deficient mice (ob/ob), chronic infusion of LEP into the lateral ventricles restored the synergy. Collectively, our findings suggest that not only h-LEP but also exogenous LEP mediates effects of ME on neural functions underlying memory, which is further enhanced by the antioxidant AX.

Treadmill exercise ameliorates the regulation of energy metabolism in skeletal muscle of NSE/PS2mtransgenic mice with Alzheimer's disease.

PURPOSE: Alzheimer's disease (AD) is classified as a progressive neurological disorder, which not only causes cognitive impairment but also abnormal weight loss, with a reduction of muscle mass related to the accumulation of amyloid-ß (Aß) in skeletal muscle. Thus, we investigated the effect of treadmill exercise on Aß deposition, and p-AMPK, p-ACC, BDNF, and GLUT4 protein levels the regulation of muscle energy metabolism using an AD mouse. METHODS: At 13 months of age, NSE/PS2m mice (Tg) and control mice (non-Tg) were assigned to non-exercise control (Con) and exercise groups (Exe). The four groups were as follows: non-Tg Con, non-Tg Exe, Tg Con, and Tg Exe. The treadmill exercise was carried out for 12 weeks. RESULTS: The highest levels of Aß expression in the skeletal muscle were in the Tg Con group. Aß expression was significantly reduced in the Tg Exe group, compared to the Tg Con group. Congo red staining showed remarkable diffuse red amyloid deposition in the Tg Con group, while Aß-deposition in the skeletal was reduced with muscle exercise in the Tg Exe group. Exercise also increased AMPK and ACC phosphorylation and BDNF and GLUT4 expression in the skeletal muscle of non-Tg and Tg mice. CONCLUSION: Treadmill exercise reduces Aß-deposition in the skeletal muscle and improves the regulation of energy metabolism. Thus, collectively, these results suggest that exercise could be a positive therapeutic strategy for skeletal muscle dysfunction in AD patients.

DNA microarray-based experimental strategy for trustworthy expression profiling of the hippocampal genes by astaxanthin supplementation in adult mouse.

Naturally occurring astaxantin (ASX) is one of the noticeable carotenoid and dietary supplement, which has strong antioxidant and anti-inflammatory properties, and neuroprotective effects in the brain through crossing the blood-brain barrier. Specially, we are interested in the role of ASX as a brain food. Although ASX has been suggested to have potential benefit to the brain function, the underlying molecular mechanisms and events mediating such effect remain unknown. Here we examined molecular factors in the hippocampus of adult mouse fed ASX diets (0.1% and 0.5% doses) using DNA microarray (Agilent 4 × 44 K whole mouse genome chip) analysis. In this study, we described in detail our experimental workflow and protocol, and validated quality controls with the housekeeping gene expression (Gapdh and Beta-actin) on the dye-swap based approach to advocate our microarray data, which have been uploaded to Gene Expression Omnibus (accession number GSE62197) as a gene resource for the scientific community. This data will also form an important basis for further detailed experiments and bioinformatics analysis with an aim to unravel the potential molecular pathways or mechanisms underlying the positive effects of ASX supplementation on the brain, in particular the hippocampus.

Astaxanthin supplementation enhances adult hippocampal neurogenesis and spatial memory in mice.

SCOPE: There is a growing necessity for efficacious natural supplements with antioxidant effects on the brain, in particular, hippocampal function. One such compound, which also has a neuroprotective effect, is the carotenoid astaxanthin (ASX). Despite ASX's potential benefit to the brain, very little is known about its effect on hippocampal plasticity and cognition. Thus, we investigated the effect of ASX on adult hippocampal neurogenesis (AHN) and spatial memory using a mouse model. METHODS AND RESULTS: Dose-response was examined in mice fed ASX-supplemented diets (0, 0.02, 0.1, and 0.5%) to define the effect of ASX on AHN. In conjunction with AHN results, hippocampus-dependent cognitive function was assessed. We delineated molecular mechanisms associated with ASX-enhanced AHN using DNA microarray analysis. Results revealed that ASX enhanced cell proliferation and survival at 0.1% and 0.5% doses. Newborn mature neurons were higher only with 0.5% ASX, which also enhanced spatial memory. Transcriptomic profiling revealed potential AHN-associated molecules (Prl, Itga4, and Il4) that were ASX induced. Their downstream factors, identified through Ingenuity Pathway Analysis, were positively correlated with ASX-induced increases in spatial memory. CONCLUSION: ASX supplementation enhanced AHN and spatial memory, and a DNA microarray approach provided, for the first time, novel molecular insights into ASX action.