bims-empneu 2021-04-18 papers

bims-empneu

Biomed News

on Exercise and Molecular Pathways Involved in Neuroprotection

Issue of 2021–04–18
ten papers selected by
Navabeh Zare-Kookandeh, Victoria University

Hippocampal PGC-1α-mediated positive effects on parvalbumin interneurons are required for the antidepressant effects of running exercise.
Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases.
Neuroplasticity and the role of exercise and diet on cognition.
Associations between physical activity, blood-based biomarkers of neurodegeneration, and cognition in healthy older adults: The MAPT study.
Molecular mechanisms of physical exercise on depression in the elderly: a systematic review.
Acute exercise and cognition: A review with testable questions for future research into cognitive enhancement with blood flow restriction.
Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats.
Association between hippocampal structure and serum brain-derived neurotrophic factor (BDNF) in healthy adults: A registered report.
The Effect of Physical Activity Interventions on Executive Function Among People with Neurodevelopmental Disorders: A Meta-Analysis.
Genistein enhances expression of extracellular regulated kinases (ERK) 1/2, and learning and memory of mouse.

Transl Psychiatry. 2021 Apr 15. 11(1): 222

Hippocampal PGC-1α-mediated positive effects on parvalbumin interneurons are required for the antidepressant effects of running exercise.

Jin Wang, Jing Tang, Xin Liang, Yanmin Luo, Peilin Zhu, Yue Li, Kai Xiao, Lin Jiang, Hao Yang, Yuhan Xie, Lei Zhang, Yuhui Deng, Jing Li, Yong Tang.

Running exercise was shown to have a positive effect on depressive-like symptoms in many studies, but the underlying mechanism of running exercise in the treatment of depression has not been determined. Parvalbumin-positive interneurons (PV+ interneurons), a main subtype of GABA neurons, were shown to be decreased in the brain during the depression. PGC-1α, a molecule that is strongly related to running exercise, was shown to regulate PV+ interneurons. In the present study, we found that running exercise increased the expression of PGC-1α in the hippocampus of depressed mice. Adult male mice with PGC-1α gene silencing in the hippocampus ran on a treadmill for 4 weeks. Then, depression-like behavior was evaluated by the behavioral tests, and the PV+ interneurons in the hippocampus were investigated. We found that running exercise could not improve depressive-like symptoms or increase the gene expression of PV because of the lack of PGC-1α in the hippocampus. Moreover, a lack of PGC-1α in the hippocampus decreased the number and activity of PV+ interneurons in the CA3 subfield of the hippocampus, and running exercise could not reverse the pathological changes because of the lack of PGC-1α. The present study demonstrated that running exercise regulates PV+ interneurons through PGC-1α in the hippocampus of mice to reverse depressive-like behaviors. These data indicated that hippocampal PGC-1α-mediated positive effects on parvalbumin interneurons are required for the antidepressant actions of running exercise. Our results will help elucidate the antidepressant mechanism of running exercise and identify new targets for antidepressant treatment.

DOI: https://doi.org/10.1038/s41398-021-01339-1
Neural Plast. 2021 ;2021 8834645

Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases.

Wojciech Kozubski, Kevin Ong, Wioletta Waleszczyk, Matthew Zabel, Jolanta Dorszewska.

Neural plasticity-the ability to alter a neuronal response to environmental stimuli-is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer's disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates in vivo including β-amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of α-synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians' diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.

DOI: https://doi.org/10.1155/2021/8834645
Am J Clin Nutr. 2021 Apr 13. pii: nqab083. [Epub ahead of print]

Neuroplasticity and the role of exercise and diet on cognition.

Nicolaas P Pronk.

DOI: https://doi.org/10.1093/ajcn/nqab083
J Gerontol A Biol Sci Med Sci. 2021 Apr 17. pii: glab094. [Epub ahead of print]

Associations between physical activity, blood-based biomarkers of neurodegeneration, and cognition in healthy older adults: The MAPT study.

MAPT/DSA Group

  Physical activity (PA) demonstrated benefits on brain health but its relationship with blood biomarkers of neurodegeneration remains poorly investigated. We explored the cross-sectional associations of physical activity with blood concentrations of neurofilament light chain (NFL) and beta amyloid (Aβ)42/40. We further examined whether the interaction between PA and these biomarkers was longitudinally related with cognition. Four-hundred and sixty-five non-demented older adults engaged in an interventional study and who had concomitant assessment of PA levels and blood measurements of NFL (pg/ml) and Aβ42/40 were analysed. A composite Z score combining 4 cognitive tests was used for cognitive assessment up to a 4-year follow-up. Multiple linear regressions demonstrated that people achieving 500-999 and 2000 + MET-min/week of PA had lower (ln)NFL concentrations than their inactive peers. Logistic regressions revealed that achieving at least 90 MET-min/week of PA was associated with lower probability of having high NFL concentrations (i.e ≥ 91.961 pg/ml (3 rd quartile)). PA was not associated with (Aβ)42/40. Mixed-model linear regressions demonstrated that the reverse relationship between PA and cognitive decline tended to be more pronounced as Aβ42/40 increased, while it was dampened with increasing levels of (ln)NFL concentrations. This study demonstrates that PA is associated with blood NFL but not with Aβ42/40. Further, it suggests that PA may attenuate the negative association between amyloid load and cognition, while having high NFL levels mitigates the favourable relationship between PA and cognition. More investigations on older adults not involved any interventional study are required for further validation of the present findings.

Keywords:  Physical exercise; aging; neurofilament light chain; plasma amyloid

DOI:  https://doi.org/10.1093/gerona/glab094
Mol Biol Rep. 2021 Apr 17.

Molecular mechanisms of physical exercise on depression in the elderly: a systematic review.

Ricardo Augusto Leoni De Sousa, Isabella Rocha-Dias, Lucas Renan Sena de Oliveira, Alex Cleber Improta-Caria, Renato Sobral Monteiro-Junior, Ricardo Cardoso Cassilhas.

  Depressive disorders are common among the elderly. Major depressive disorder will be one of the highest healthcare costs in middle and higher income countries by 2030. It is known that physical inactivity leads to negative effects on mental health in the elderly.The purpose of this review was to explore investigate the consequences of physical exercise (aerobic and resistance exercise) on major depressive disorder among elderly, and presenting its potential biological mechanisms. This study was designed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials or randomized clinical trials or cohort studies participated of the study design. Ten studies were evaluated and the main outcomes of each were reported. Aerobic and resistance training revealed to be effective in fighting the symptoms of depression. The most common physical exercise protocol adopted to reduce the consequences of major depressive disorder in humans was the prescription of aerobic exercise at moderate-intensity lasting 60 min per session, 3 times per week, for 24 weeks. Physical exercise enhances IGF-I and activates PGC-1α/FNDC5/Irisin pathway. Physical exercise also increases expression of BDNF and its receptor, TrkB, in the hippocampus and prefrontal cortex leading to upstream of ERK and inhibiting depressive-like behavior. Physical exercise brings mental health benefits and plays a crucial role in avoiding the development of major depressive disorder.

Keywords:  Lifestyle; Mood disorder; Older; Physical activity

DOI:  https://doi.org/10.1007/s11033-021-06330-z
Med Hypotheses. 2021 Apr 01. pii: S0306-9877(21)00104-3. [Epub ahead of print]151 110586

Acute exercise and cognition: A review with testable questions for future research into cognitive enhancement with blood flow restriction.

Yujiro Yamada, Emily M Frith, Vickie Wong, Robert W Spitz, Zachary W Bell, Raksha N Chatakondi, Takashi Abe, Jeremy P Loenneke.

  Blood flow restriction, in combination with low load/intensity exercise, has consistently been shown to increase both muscle size and strength. In contrast, the effects of blood flow restricted exercise on cognition have not been well studied. Therefore, the purpose of this paper is 1) to review the currently available literature investigating the impact of blood flow restricted exercise on cognition and 2) to provide some hypotheses for how blood flow restriction might provide an additive stimulus for augmenting specific cognitive domains above exercise alone. Given the lack of research in this area, the effects of blood flow restricted exercise on cognition are still unclear. We hypothesize that blood flow restricted exercise could potentially enhance several cognitive domains (such as attention, executive functioning, and memory) through increases in lactate production, catecholamine concentration, and PGC-1α expression. We review work that suggests that blood flow restriction is not only a beneficial strategy to improve musculoskeletal function but could also be a favorable method for enhancing multiple domains of cognition. Nonetheless, it must be emphasized this is a hypothesis that currently has only minimal experimental support, and further investigations in the future are necessary to test the hypothesis.

Keywords:  Attention; Brain-derived neurotrophic factor; Executive function; Lactate; Memory

DOI:  https://doi.org/10.1016/j.mehy.2021.110586
Biomed Pharmacother. 2021 Apr 08. pii: S0753-3322(21)00362-0. [Epub ahead of print]139 111577

Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats.

Masoud Rahmati, Maryam Keshvari, Rahim Mirnasouri, Farzaneh Chehelcheraghi.

   INTRODUCTION: Diabetes mellitus is related to cognitive impairments and molecular abnormalities of the hippocampus. A growing body of evidence suggests that Urtica dioica (Ud) and exercise training (ET) have potential therapeutic effects on diabetes and its related complications. Therefore, we hypothesized that the combined effect of exercise training (ET) and Ud might play an important role in insulin signaling pathway, oxidative stress, neuroinflammation, and cognitive impairment in diabetic rats.
METHODS: Forty animals were divided into five groups (N = 8): healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-exercise training (D-ET), diabetes-Urtica dioica (D-Ud), diabetes-exercise training-Urtica dioica (D-ET-Ud). Streptozotocin (STZ) (Single dosage; 45 mg/kg, i.p.) was used to induce diabetes. Then, ET (moderate intensity/5day/week) and Ud extract (50 mg/kg, oral/daily) were administered for six weeks. We also investigated the effects of ET and Ud on cognitive performance (assessed through Morris Water Maze tests), antioxidant capacity, and lipid peroxidation markers in hippocampus. Furthermore, we measured levels of insulin sensitivity and signaling factors (insulin-Ins, insulin receptor-IR and insulin-like growth factor-1 receptor-IGF-1R), and neuroinflammatory markers (IL-1 β, TNF-α). This was followed by TUNEL assessment of the apoptosis rate in all regions of the hippocampus.
RESULTS: D-sed rats compared to H-sed animals showed significant impairments (P < 0.001) in hippocampal insulin sensitivity and signaling, oxidative stress, neuroinflammation, and apoptosis, which resulted in cognitive dysfunction. Ud extract and ET treatment effectively improved these impairments in D-ET (P < 0.001), D-Ud (P < 0.05), and D-ET-Ud (P < 0.001) groups compared to D-sed rats. Moreover, diabetes mediated hippocampal oxidative stress, neuroinflammation, insulin signaling deficits, apoptosis, and cognitive dysfunction was further reversed by chronic Ud+ET administration in D-ET-Ud rats (P < 0.001) compared to D-sed animals.
CONCLUSIONS: Ud extract and ET ameliorate cognitive dysfunction via improvement in hippocampal oxidative stress, neuroinflammation, insulin signaling pathway, and apoptosis in STZ-induced diabetic rats. The results of this study provide new experimental evidence for using Ud+ET in the treatment of hippocampal complications and cognitive dysfunction caused by diabetes.

Keywords:  Apoptosis; Cognitive performance; Diabetes; Exercise; Hippocampus; Urtica dioica

DOI:  https://doi.org/10.1016/j.biopha.2021.111577
Neuroimage. 2021 Apr 11. pii: S1053-8119(21)00288-3. [Epub ahead of print] 118011

Association between hippocampal structure and serum brain-derived neurotrophic factor (BDNF) in healthy adults: A registered report.

L M C Puhlmann, R Linz, S L Valk, P Vrticka, R Vos de Wael, A Bernasconi, N Bernasconi, B Caldairou, I Papassotiriou, G P Chrousos, B C Bernhardt, T Singer, V Engert.

  The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce, and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus, and is implicated in adult neurogenesis in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 301, 174 f) with a broad age range (20-55 years, mean 40.7) recruited in the context of the ReSource project. We related HCV to basal sBDNF and, in a subsample (n = 113, 65 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null-results provide a first reference point on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.

Keywords:  Hippocampal volume; brain-derived neurotrophic factor (BDNF); dentate gyrus; hippocampal subfields; neurotrophins; stress-reactive BDNF

DOI:  https://doi.org/10.1016/j.neuroimage.2021.118011
J Autism Dev Disord. 2021 Apr 15.

The Effect of Physical Activity Interventions on Executive Function Among People with Neurodevelopmental Disorders: A Meta-Analysis.

Ming-Chih Sung, Byungmo Ku, Willie Leung, Megan MacDonald.

  The current meta-analysis comprehensively examined the effects of physical activity interventions on executive function among people with neurodevelopmental disorders. The meta-analysis included 34 studies with 1058 participants aged 5-33 years. Results indicated an overall significant medium effect of physical activity interventions on improving executive function in people with neurodevelopmental disorders under the random-effect model (Hedges' g = 0.56, p < .001). Significant moderators of the effects of physical activity intervention on executive function included age, intervention length and session time, executive function subdomains, and intervention dose (total minutes in the intervention). This meta-analysis provides support for the effectiveness of physical activity interventions on executive function among people with neurodevelopmental disorders. Future studies and limitations are discussed.

Keywords:  ADHD; ASD; Cognition; Disability; Exercise intervention

DOI:  https://doi.org/10.1007/s10803-021-05009-5
IBRO Neurosci Rep. 2021 Jun;10 90-95

Genistein enhances expression of extracellular regulated kinases (ERK) 1/2, and learning and memory of mouse.

Kurrey Khuleshwari, Paramanik Vijay.

  Genistein (GEN) is a well known phytoestrogen. It acts through estrogen receptor (ER) and performs plethora of functions in the brain. ERK1/2 is an activated kinase which involves in neuron differentiation, adult neurogenesis and several brain functions including learning and memory. However, GEN dependent expression of ERK1/2 and its effect in learning and memory of mice are unknown. In this study, Swiss albino male mice of 25weeks weighing 30 g were used for the experiments. Mice were placed in two groups- control (C) and genistein treated (GEN). Treated group received GEN dissolved in sesame oil (1 mg/kg/day) whereas the control group received sesame oil only. To study the effects of GEN on learning and memory, open-field (OF) test and novel object recognition (NOR) test were performed. Moreover, immunoblotting (IB) was performed to check the expression of ERK1/2 in the mouse brain of both groups. In the OF test, no significant change was observed in motor activity and anxiety in GEN treated mice as compared to control. Moreover, NOR test suggested that entry towards the dissimilar object was higher in case of GEN treated mice as compared to control. These findings suggest higher learning and memory of GEN treated mice than of control. IB showed that the expression of ERK1/2 was significantly high in GEN treated mouse brain as compared to control. Such study may be helpful to understand GEN mediated learning and memory involving ERK1/2.

Keywords:  Brain; ERK1/2; Genistein; Immunoblotting; Learning and memory; Novel Object Recognition; Open field

DOI:  https://doi.org/10.1016/j.ibneur.2021.01.005