Journal of Exercise & Organ Cross Talk

Abstract Multiple sclerosis (MS) is a chronic neurological disease associated with neurodegeneration and impaired neurotrophic support. Neuromuscular training, through integrated activation of the nervous and muscular systems, may positively influence these neurotrophic factors. Therefore, this study investigated the effect of combined training on serum BDNF and GDNF levels in individuals with multiple sclerosis. Thirty women with multiple sclerosis (mean age: 36.2±5.8 years; BMI: 22.1±4.2 kg/m²) were purposively selected and randomly assigned to an experimental group (n=15) or a control group (n=15). The experimental group completed an eight-week combined training program (three sessions per week), consisting of core stability, resistance, balance, and agility exercises with progressive overload, while exercise intensity was controlled using the Borg perceived exertion scale., while the control group continued their usual daily activities. Blood samples were collected 24 hours before and 48 hours after the final training session, and the obtained serum was used to measure BDNF and GDNF levels. Data were analyzed using repeated-measures analysis of variance with a significance level of 0.05, employing SPSS software (version 27). The results demonstrated that neuromuscular training induced significant increases in serum BDNF (p=0.001, η²=0.80) and GDNF (p=0.001, η²=0.79) levels in the experimental group compared with the control group. Overall, the results of this study demonstrate that eight weeks of neuromuscular training elicit significant increases in serum BDNF and GDNF levels in women with multiple sclerosis. These findings indicate an enhanced neurotrophic environment that may support neural plasticity and neuroprotective mechanisms. Accordingly, neuromuscular training appears to be a safe and effective non-pharmacological strategy for improving neural health and potentially attenuating neurological dysfunctions associated with multiple sclerosis.

Abstract Unmanaged Type 2 Diabetes (DM2) is a known risk factor for cognitive decline, dementia, and Alzheimer's disease (DM3). This study explores the combined effects of high-intensity interval training (HIIT) and thyme honey on the expression of genes involved in memory-related signaling pathways (BDNF-TrkB-CREB), which are compromised in both DM2 and DM3. This experimental study involved 36 young male Wistar rats, divided into four groups: control (C), HIIT (T), thyme honey (H), and HIIT-thyme honey (TH). The T and TH groups underwent 40 training sessions over two months, with progressively increasing intervals (from 2 to 8) and intensity (from 80% to 95% of maximum running speed). Concurrently, the H and TH groups were administered 3 g/kg of thyme honey 5 days a week. Changes in BDNF, TrkB, and CREB gene expression were assessed using RT-PCR. The data were analyzed through one-way ANOVA, Bonferroni post hoc test, and Univariate analysis using SPSS-22 software. A significant increase in BDNF and CREB expression in the interactive intervention group and the expression of the TrkB gene in honey intervention groups were observed compared to diabetic control (P≥0.001). The interactive intervention with HIIT exercises and thyme honey has a synergistic effect on increasing gene expression in memory-related pathways. The highest effect size was observed for HIIT training on BDNF (EF=0.667) and CREB (EF=0.540), while the honey intervention showed a significant effect size on TrkB (EF=0.666).

Abstract Dear Editor-in-Chief
 
Based on recent studies, it is now clear that there is a muscle–brain endocrine loop that can be partly mediated by myokine signaling. There are also other metabolites as mediators which can affect circulating compounds (Rai & Demontis, 2016) and these include noncoding RNAs (Makarova et al., 2014), hormone-associated responses, as well as, muscular enzymes (Pedersen, 2019). Brain-Derived Neurotrophic Factor (BDNF) is considered to be a key role in helping to mediate the impacts of exercise on the hippocampus (Loprinzi & Frith, 2019). Studies conducted on laboratory rats showed an increase in BDNF mRNA and BDNF protein in the hippocampus of these animals when wheel running exercise was performed for 1 to 8 weeks (Adlard, Perreau, & Cotman, 2005; Farmer et al., 2004; Liu & Nusslock, 2018; Neeper, Góauctemez-Pinilla, Choi, & Cotman, 1995; Oliff, Berchtold, Isackson, & Cotman, 1998; Van Hoomissen, Chambliss, Holmes, & Dishman, 2003). In terms of cognitive functions, i.e. memory and learning, BDNF has also been demonstrated to be effective in the improvement of such functions (Vaynman, Ying, & Gomez‐Pinilla, 2004; Vaynman, Ying, & Gómez‐Pinilla, 2004).
Research on humans indicates that their brains can release BDNF while cycling (Rasmussen et al., 2009; Seifert et al., 2010), also in another study in healthy people as well as people with schizophrenia who had been training in aerobic exercise for three months, the level of BDNF increased in their hippocampus by 12% and 16%, respectively (Pajonk et al., 2010). As a growth factor for the hippocampus, BDNF plays a significant role in learning and improving cell survival (Wrann et al., 2013). Interestingly enough, research findings show that BDNF can also be expressed in skeletal muscle tissues during exercise in humans; nonetheless, it is not clear whether muscle-derived BDNF can get into the bloodstream from the muscle to create a direct interaction between muscle and brain (Matthews et al., 2009).
Some fascinating studies indicate that irisin and myokines cathepsin-B might cross the (BBB) blood-brain barrier, and consequently, BDNF levels may increase. In recent a study conducted by Moon et al. (Moon et al., 2016) a novel myokine, cathepsin B (CTSB) was identified. Other work also demonstrated that exercise can increase CTSB systemic level, therefore, BDNF expression will be promoted in the hippocampus and lead to the formation of nerve tissue as well. Running on a treadmill for four months increased CTSB plasma levels, as well as CTSB gene expression in humans, mice, and rhesus monkeys. In addition, it was indicated that CTSB could cross BBB in mice. In studies by Moon et al. (2016) on CTSB knockout mice, it was made clear that mice without CTSB refused to do voluntary exercise regarding hippocampal growth and cognitive development. It is not clear whether myokine CTSB can lead to cognitive function development in humans regarding exercise training or not (Moon et al., 2016; Suzuki, 2016).
The PGC-1α-dependent myokine irisin, which is famous for its browning impacts (Boström et al., 2012), can play a role in the intervention of the brain’s physical activity (Wrann et al., 2013). An excessive expression of irisin in the primary cortical neurons can cause a higher BDNF expression, while FNDC5 knockdown mediated by RNAi can cause a lower BDNF expression. Furthermore, irisin delivery to the mice’s liver by adenoviral vectors will raise the systemic irisin level, consequently resulting in a higher level of BDNF in the hippocampus. Whether doing exercise can increase irisin plasma concentration in humans (Albrecht et al., 2015; Wrann, 2015), and whether irisin is affected by a muscle–brain endocrine loop is a disputable issue.

Abstract The purpose of this research was to conduct a systematic review and meta-analysis on the effect of exercise training on neurotrophin levels in obese and overweight individuals. The research evaluated the effect of exercise training on neurotrophins in the databases of PubMed, Science Direct, Scopus, and Google Scholar with identified keywords among papers published from 2000 onwards. After preliminary screening, full-text studies as well as critical evaluation of the papers meeting the inclusion criteria were analyzed. Finally, 12 studies entered systematic research, and 6 studies entered meta-analysis research. The results show that exercise training has an addictive effect on neurotrophin levels in obese individuals, but this addictive effect is not significant. The present meta-analyze shows that the brain -Derived Neurotrophic Factor (BDNF) response to exercise in obese individuals is increasing, but the increase is not significant (Difference in means = -0.42 pg/ml, P = 0.460). On the other hand, the Nerve Growth Factor (NGF) response to exercise is also increasing which is significant (Z = 2.12, P = 0.034).  Thus, it can be concluded that exercise cannot increase neurotrophins in obese and overweight individuals; although, further studies are needed in this area.

Abstract Dear Editor-in-Chief
The world has recently experienced one of the hardest pandemics, COVID-19. Clinical signs of this disease include fever, dry cough, and diarrhea, or different symptoms that lead to acute respiratory distress syndrome with a further increase in the severity of the disease. Although the first observations of this disease are the involvement of symptoms and respiratory and heart injuries, various studies have also shown the nerve damage caused by this disease. Common neurological symptoms include headache, dizziness, anosmia, seizures, or paralysis. The elderly and critically ill are in the high-risk group and have shown severe neurological symptoms after COVID-19. Apart from COVID-19-induced cellular and neurological damage, this disease has a profound effect on the mental health of people around the world. Increasing the duration of this disease and staying at home causes social and economic problems and as a result mental health problems (Verma et al., 2020). Neurological and mental illnesses are very common all over the world.
Psychological resilience was an important issue during COVID-19 epidemic. In other words, during an epidemic, mental health of people should be consider and cheeked, and entertainment programs should be prevented from causing psychological damage. Research during the COVID-19 epidemic found that because of the psychological pressures to increase psychological resilience, people tended to be more exposed to the outdoors, exercise more, receive more social support from family, friends and important people, sleep better, and pray more, that these factors were effective in mitigating psychological trauma. In most studies, spiritual health affects mental health, because repeated prayers and worships have been more independently associated with psychological resilience (Killgore et al., 2020). In other words, those who actively participate in these spiritual activities and strengthen their relationship with God are found to have the most psychological resilience to the mental health challenges imposed by COVID-19. In addition, the effects of exercise at the cellular level can help improve memory and psyche and be effective in improving psychological resilience. To date, no studies have been performed on secretions due to muscle contraction and its effect on the brain and psychological function, and psychological resilience especially to control the psychological damage caused by an epidemic.
Exercise has many beneficial effects on brain health and helps reduce the risks of dementia, depression, and stress, and is involved in restoring and maintaining cognitive function and metabolic control. The fact that exercise is sensed by the brain suggests that environmental factors induced by the muscle allow a direct link between muscle function and the brain. Muscles secrete myokines that help regulate hippocampal function. Evidence is accumulating that myokine cathepsin B crosses the blood-brain barrier to increase brain-derived neurotrophic factor production, resulting in neurogenesis, memory, and learning. In addition, the muscle tissue itself can affect the central nervous system, memory, and psyche in form of endocrine by increasing BDNF expression. Exercise also increases the expression of the neurogenic gene FNDC5 (which encodes myogenic FNDC5-dependent PGC1α), which in turn can help increase levels of brain-derived neurotrophic factor (Pedersen, 2019).
Serum levels of myokine, IL-6, increase with exercise and may have beneficial effects on the central nervous system. Exercise also increases PGC1α-dependent muscle expression and the enzymes kynurenine aminotransferase, which beneficially alters the balance between the neurotoxic kynurenine and the neuroprotective Kynurenic acid, thereby reducing depressive symptoms. Signaling myokine and other muscle factors and exercise-induced hepatokines and adipokines play a role in the beneficial effects of exercise on neurogenesis, cognitive function, appetite, and metabolism, thus supporting the existence of a muscle-brain endocrine axis. Also, it can affect psychological resilience which needs more studies.