bims-empneu Biomed News
on Exercise and Molecular Pathways Involved in Neuroprotection
Issue of 2021–05–16
eleven papers selected by
Navabeh Zare-Kookandeh, Victoria University



  1. Cereb Cortex. 2021 May 13. pii: bhab093. [Epub ahead of print]
      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.
    Keywords:  adult hippocampal neurogenesis; high-intensity intermittent training; spatial memory
    DOI:  https://doi.org/10.1093/cercor/bhab093
  2. Neurosci Lett. 2021 May 08. pii: S0304-3940(21)00327-X. [Epub ahead of print]756 135949
      It has been suggested that gut microbiota dysbiosis can lead to Alzheimer's disease (AD), inducing the production of many AD-related pre-inflammatory cytokines. On the other hand, daily probiotic administration and regular exercise training are assumed to improve clinical AD-related symptoms. To take this line of research further, this study was aimed at investigating the impact of moderate-intensity interval training (MIIT) with a combined administration of Lactobacillus plantarum and Bifidobacterium bifidum (probiotic, BROB) on the passive avoidance test (Shuttle Box), choline acetyltransferase (ChAT) and the brain derived neurotrophic factor (BDNF) in the hippocampus of a rat model of AD. Forty male Wistar rats (280 ± 20 g) were divided into five groups (n = 8 in each) of control, amyloid beta peptide (Aβ), Aβ + MIIT (AD rats undergoing MIIT), Aβ + PROB (AD rats fed Lactobacillus plantarum and Bifidobacterium bifidum), and Aβ + MIIT + PROB (AD rats receiving both treatments). AD was induced by the intra-cerebroventricular injection of Aβ1-42 peptide. MIIT was performed on rodent treadmill for 8 weeks (5 days per week). The probiotic was also fed daily to the related groups for 8 weeks. BDNF and ChAT in the hippocampus were measured by real time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. Cresyl violet staining of brain tissue was performed to evaluate the dead cells. Results of tissue staining showed that the induction of the Alzheimer's led to the destruction of hippocampal cells and induced neurodegeneration (p = 0.001). Results of the shuttle box test showed that short-term memory was improved in the Aβ + MIIT + PROB group compared to the Aβ group, while death cells (dark cells) were decreased in all the other three groups (MIIT, BROB, and Aβ + MIIT + PROB). Levels of ChAT as well as the BDNF mRNA in the Aβ + MIIT + PROB group showed a significant increase compared to the Aβ group. In conclusion, it seems that the use of the combined administration of Lactobacillus plantarum and Bifidobacterium bifidum with interval aerobic exercise can have neuroprotective effects on AD.
    Keywords:  Alzheimer’s disease; BDNF gene; Bifidobacterium bifidum; Lactobacillus plantarum; Moderate-intensity interval training; Probiotics
    DOI:  https://doi.org/10.1016/j.neulet.2021.135949
  3. Front Hum Neurosci. 2021 ;15 620958
      Previous research has demonstrated that regular exercise modulates motor cortical plasticity and cognitive function, but the influence of short-term high-intensity interval training (HIIT) remains unclear. In the present study, the effect of short-term HIIT on neuroplasticity and executive function was assessed in 32 sedentary females. Half of the participants undertook 2 weeks of HIIT. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure motor cortical plasticity via short intracortical inhibition (SICI) and intracortical facilitation (ICF). We further adapted the Stroop task using functional near-infrared spectroscopy (fNIRS) to evaluate executive function in the participants. The results indicated that, compared with the control group, the HIIT group exhibited decreased ICF. In the Stroop task, the HIIT group displayed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left orbitofrontal cortex (OFC) even though no significant difference in task performance was observed. These findings indicate that short-term HIIT may modulate motor cortical plasticity and executive function at the neural level.
    Keywords:  executive function; high-intensity interval training; intracortical facilitation; sedentary females; short intracortical inhibition
    DOI:  https://doi.org/10.3389/fnhum.2021.620958
  4. J Clin Endocrinol Metab. 2021 May 13. pii: dgab333. [Epub ahead of print]
      The worlds' population is aging leading to increased rates of neurodegenerative disorders. Exercise has countless health benefits and has consistently been shown to improve brain health and cognitive function. The purpose of this review is to provide an overview of exercise-induced adaptations in the brain with a focus on crosstalk between peripheral tissues and the brain. We highlight recent studies into exercise-induced circulating factors, or exerkines, including irisin, cathepsin B, GPLD1, ketones, and the mechanisms mediating their effects in the brain.
    Keywords:  BDNF; BRAIN; EXERCISE; FGF21; GDF15; GPLD1; IRISIN
    DOI:  https://doi.org/10.1210/clinem/dgab333
  5. Brain Res Bull. 2021 May 05. pii: S0361-9230(21)00130-1. [Epub ahead of print]172 203-211
      Autophagy is a highly regulated intracellular process for the degradation of protein aggregates and damaged organelles. Recently, autophagy has been implicated in Alzheimer's disease (AD) and aging. Autophagy process is regulated by the recruitment and assembly of several autophagy-related genes (Atgs) such as, Atg7 and LC3, as the highly conserved and important markers involved in the regulation of autophagy. We recently reported the reduced LC3-II/LC3-I ratio, down-regulated ATG7, and increased p62 protein levels in hippocampal tissues of aging rats. MicroRNA-130a (miR-130a) plays a crucial role in physiological and pathological processes, but whether miR-130a affects the autophagy of brain is unknown. We aim to explore the regulatory role of miR-130a on the autophagy and cell senescence of SH-SY5Y, as well as LC3-II/LC3-I ratio, and the expression of p62, ATG7, Ac-p53 and p21 during exercise intervention of aging rats. In this study, miR-130a expression was markedly down-regulated in the hippocampal of aged rats companying with up-regulated expression of Ac-p53 and p21 when compared with young rats. In contrast, voluntary wheel running could up-regulate miR-130a expression; decrease the expression of Ac-p53 and p21 in aging rats. Interestingly, exercise reversed the impaired autophagy resulted from aging possibly by activating AMPK signaling. Moreover, overexpression of miR-130a in d-galactose (D-gal)-induced SH-SY5Y cell senescence model attenuated d-gal-induced impaired autophagy and cell senescence, demonstrated by decreased levels of LC3, Ac-p53, p21 and increased p62, suggesting that voluntary wheel running can alleviate brain aging in natural aging rats by up-regulating miR-130a-mediated autophagy.
    Keywords:  Autophagy; Brain aging; Voluntary wheel-running exercise; miR-130a
    DOI:  https://doi.org/10.1016/j.brainresbull.2021.04.027
  6. Exp Gerontol. 2021 May 06. pii: S0531-5565(21)00166-2. [Epub ahead of print]150 111384
       INTRODUCTION: Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. Exercise training, which is incorporated both goal-based training such as task-oriented training (TOT) and aerobic training (AT), has been suggested to induce neuroprotection. However, molecular mechanisms which may underlie exercise-induced neuroprotection are still largely unknown. Thus, the aim of the present study was to investigate the effects of TOT combined with AT (TOT-AT) on serum brain-derived neurotrophic factor (BDNF), glial cell-derived growth factor (GDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels in people with PD (PwPD).
    METHODS: Forty PwPD were randomized into 8-week of either exercise group (n = 20) or control group (n = 20). The exercise group received TOT-AT while the control group received only AT. Serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1β levels determined with ELISA were assessed at baseline and after training.
    RESULTS: A total of 29 PwPD completed this study. Our results showed no significant change in the serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1β levels in both groups. After the intervention period, no significant difference was observed between the groups regarding the serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1β levels.
    CONCLUSION: TOT-AT could not be an effective exercise method for changing serum concentrations of BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1β in the rehabilitation of PD.
    Keywords:  Exercise; Neurotrophic factors; Parkinson's disease; Proinflammatory cytokines
    DOI:  https://doi.org/10.1016/j.exger.2021.111384
  7. Mol Psychiatry. 2021 May 14.
      Adult hippocampal neurogenesis (AHN) represents a remarkable form of neuroplasticity that has increasingly been linked to the stress response in recent years. However, the hippocampus does not itself support the expression of the different dimensions of the stress response. Moreover, the main hippocampal functions are essentially preserved under AHN depletion and adult-born immature neurons (abGNs) have no extrahippocampal projections, which questions the mechanisms by which abGNs influence functions supported by brain areas far from the hippocampus. Within this framework, we propose that through its computational influences AHN is pivotal in shaping adaption to environmental demands, underlying its role in stress response. The hippocampus with its high input convergence and output divergence represents a computational hub, ideally positioned in the brain (1) to detect cues and contexts linked to past, current and predicted stressful experiences, and (2) to supervise the expression of the stress response at the cognitive, affective, behavioral, and physiological levels. AHN appears to bias hippocampal computations toward enhanced conjunctive encoding and pattern separation, promoting contextual discrimination and cognitive flexibility, reducing proactive interference and generalization of stressful experiences to safe contexts. These effects result in gating downstream brain areas with more accurate and contextualized information, enabling the different dimensions of the stress response to be more appropriately set with specific contexts. Here, we first provide an integrative perspective of the functional involvement of AHN in the hippocampus and a phenomenological overview of the stress response. We then examine the mechanistic underpinning of the role of AHN in the stress response and describe its potential implications in the different dimensions accompanying this response.
    DOI:  https://doi.org/10.1038/s41380-021-01136-8
  8. Adv Exp Med Biol. 2021 ;1269 295-300
      It has been reported that the cardiovascular response in the supine position is different from that in the sitting position. However, there are few reports on the effects of posture on cerebral oxygenation during exercise. Cycling exercises change oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) levels in motor-related areas. Therefore, this study compared O2Hb levels at motor-related areas during recumbent versus supine cycling. Eleven healthy young male performed a 30-min cycling exercise protocol at 50% of the maximal oxygen uptake (VO2 max) in the recumbent and supine positions. Near-infrared spectroscopy (NIRS) was used to measure exercise-induced O2Hb and HHb changes in the right (R-PMA) and left premotor areas (L-PMA), supplementary motor area (SMA), and primary motor cortex (M1). In R-PMA, L-PMA and SMA, the O2Hb obtained during supine cycling was significantly higher than that during recumbent cycling (R-PMA, 0.031 ± 0.01 vs. 0.693 ± 0.01; L-PMA, 0.027 ± 0.01 vs. 0.085 ± 0.013; SMA, 0.041 ± 0.011 vs. 0.076 ± 0.008 mM·cm, recumbent vs. supine position; p < 0.05). These results suggest that supine cycling exercise increases R-PMA, L-PMA, and SMA O2Hb levels in healthy young men.
    Keywords:  Near-infrared spectroscopy; Oxygenated hemoglobin; Premotor area; Primary motor cortex; Supplementary motor area
    DOI:  https://doi.org/10.1007/978-3-030-48238-1_47
  9. Mol Psychiatry. 2021 May 14.
      In addition to its role as a neuronal energy substrate and signaling molecule involved in synaptic plasticity and memory consolidation, recent evidence shows that lactate produces antidepressant effects in animal models. However, the mechanisms underpinning lactate's antidepressant actions remain largely unknown. In this study, we report that lactate reverses the effects of corticosterone on depressive-like behavior, as well as on the inhibition of both the survival and proliferation of new neurons in the adult hippocampus. Furthermore, the inhibition of adult hippocampal neurogenesis prevents the antidepressant-like effects of lactate. Pyruvate, the oxidized form of lactate, did not mimic the effects of lactate on adult hippocampal neurogenesis and depression-like behavior. Finally, our data suggest that conversion of lactate to pyruvate with the concomitant production of NADH is necessary for the neurogenic and antidepressant effects of lactate.
    DOI:  https://doi.org/10.1038/s41380-021-01122-0
  10. Comb Chem High Throughput Screen. 2021 May 06.
       AIM: The aim of this study was to investigate the effect, and molecular mechanism of Scutellaria Baicalensis Georgi stems and leaves flavonoids (SSF) in promoting neurogenesis and improving memory impairment induced by the PI3K-AKT-CREB signaling pathway.
    METHODS: Alzheimer's disease (AD) was induced in the male Wistar rats by intracerebroventricular injection of amyloid beta-peptide 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ). The Morris water maze was used to screen the successful establishment of the memory impairment model of rats. The screened successful model rats were randomly divided into a model group and three groups of three different doses of the drug (SSF). Rats in the drug group were treated with 35, 70, and 140 mg/kg of SSF for 43 days. The Eight-arm maze was used to measure the spatial learning and memory abilities of the rat, including working memory errors (WME) and reference memory errors (RME). Immunohistochemistry was used to detect the expression of BrdU, an indicator of neuronal proliferation, in the hippocampal gyrus of rats. The mRNA and protein expressions of TRKB, PI3K, AKT, P-AKT, and IGF2 in the PI3K-AKT-CREB signaling pathway in the hippocampus and cerebral cortex of the rats were determined by quantitative real-time PCR (qPCR) and Western blotting methods.
    RESULTS: Compared to the sham group, the spatial memory ability of rats with composited Aβ was decreased, the number of WME and RME (P < 0.01) was increased, the expression of BrdU protein (P < 0.01) in the hippocampal gyrus was reduced, the mRNA and protein expression levels of TRKB, AKT, and IGF2 (P < 0.01, P < 0.05) in the hippocampus and cerebral cortex were lowered, and the mRNA expression level of PI3K (P < 0.01) in the cerebral cortex and the protein expression level of PI3K (P < 0.01) in the hippocampus were augmented. However, compared to the model group, the three-doses of SSF improved memory disorder induced by composited Aβ, reduced the number of WME and RME, increased the expression of BrdU protein in the hippocampal gyrus, and differently regulated the mRNA and protein expressions in composited Aβ rats.
    CONCLUSION: SSF improved memory impairment and neurogenesis disorder induced by composited Aβ in rats by activating the PI3K-AKT-CREB signaling pathway and up-regulating the mRNA and protein expressions of TRKB, PI3K, AKT, CREB, and IGF2.
    DOI:  https://doi.org/10.2174/1386207324666210506152320