The Impact of Normobaric Hypoxia and Intermittent Hypoxic Training on Cardiac Biomarkers in Endurance Athletes: A Pilot Study.

This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium's response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes.

Hepcidin and erythroferrone response to 3 weeks of exposure to normobaric hypoxia at rest in trained cyclists.

Purpose: The effectiveness of altitude training on haematological adaptations is largely dependent on iron metabolism. Hepcidin and erythroferrone (ERFE) are key iron-regulating hormones, yet their response to altitude training is poorly understood. The aim of this study was to analyze changes in hepcidin and ERFE under the influence of 3 weeks of the Live High-Train Low (LH-TL) method. Methods: Twenty male trained cyclists completed a 3-week training program under normoxic conditions (NORM) or with passive exposure to normobaric hypoxia (LH-TL; FiO2 = 16.5%, ∼2000 m; 11-12 h/day). Hepcidin, ERFE, hypoxia inducible factor-2 (HIF-2), ferroportin (Fpn), erythropoietin (EPO), serum iron (Fe) and hematological variables were assessed at baseline (S1), then immediately after (S2) and 3 days after (S3) intervention. Results: In the LH-TL group, hepcidin decreased by 13.0% (p < 0.001) in S2 and remained at a reduced level in S3. ERFE decreased by 28.7% (p < 0.05) in S2 and returned to baseline in S3. HIF-2α decreased gradually, being lower by 25.3% (p < 0.05) in S3. Fpn decreased between S1 and S2 by 18.9% (p < 0.01) and remained lower during S3 (p < 0.01). In the NORM group, in turn, hepcidin levels increased gradually, being higher by 73.9% (p < 0.05) in S3 compared to S1. No statistically significant differences in EPO were observed in both groups. Conclusion: Three weeks of LH-TL suppresses resting hepcidin and ERFE levels in endurance athletes. We found no association between hepcidin and ERFE after LH-TL. Probably, ERFE is not the only factor that suppresses hepcidin expression in response to moderate hypoxia, especially in later stages of hepcidin downregulation. With the cessation of hypoxia, favorable conditions for increasing the availability of iron cease.

Slowing of EEG waves correlates with striatal [18 F]fluorodopa PET/CT uptake and executive dysfunction in Parkinson's disease.

Parkinson's disease (PD) research on specific neuroimaging and neurophysiological biomarkers revealing executive dysfunction mechanisms is limited, necessitating validation. Thus, our study aimed to assess associations between electroencephalographic power spectral density (PSD-EEG), striatal [18 F]Fluorodopa uptake and neuropsychological executive function (EF) testing parameters in PD, while also estimating their diagnostic accuracy. We compared resting PSD-EEG, striatal [18 F]Fluorodopa uptake ratios based on positron emission computed tomography ([18 F]FDOPA PET/CT) and neuropsychological EF tests outcomes [Trail Making Test (TMT) and Stroop Test (ST)] between PD patients and healthy controls (HCO) and then calculated correlations among these measures separately for each group. Additionally, we estimated PD diagnostic accuracy of the PSD-EEG and [18 F]FDOPA PET/CT parameters. In PD patients, we observed the following: (i) slower EEG waves, reflected in increased power of the EEG theta and lower-alpha bands in frontal lobe areas; (ii) reduced [18 F]FDOPA PET/CT uptake in the putaminal and caudate nuclei, along with a decreased putamen-to-caudate ratio ([18 F]FDOPA PET/CT PCR); and (iii) longer performance times evident in nearly all EF tests' parameters. Slower EEG waves correlated negatively with [18 F]FDOPA PET/CT PCR and positively with most of the EF test parameters. Furthermore, we found negative correlations between [18 F]FDOPA PET/CT PCR and certain EF measures related to ST. [18 F]FDOPA PET/CT ratios and several PSD-EEG parameters, particularly those from the prefrontal cortex, demonstrated clinically reasonable diagnostic accuracy for PD. In conclusion, EEG waves slowing in the frontal lobe were correlated with striatal dopaminergic deficiency and impaired executive function in mild PD patients and showed promise as a biomarker of PD-related executive dysfunction.

The Impact of Acute Mild Normobaric Hypoxia and a Single Bout of Exercise to Volitional Exhaustion on Cognitive Performance in Endurance and Strength-Trained Athletes: The role of BDNF, EP-1, Catecholamines and Lactate.

The aim of the study was to examine whether a single bout of exercise to volitional exhaustion, performed under moderate normobaric hypoxia (H), would affect psychomotor performance (PP) in differently trained athletes. For this purpose, ten strength-trained (S) athletes, ten endurance-trained (E) athletes and ten healthy men leading a sedentary lifestyle as a control (C) group performed voluntarily two graded exercise tests until volitional exhaustion (EVE) under normoxia (N) and H (FiO2 = 14.7%). We measured the peripheral level of the brain derived neurotrophic factor (BDNF), choice reaction time (CRT) and the number of correct reactions (NCR) as indices of PP. Psychomotor tests were performed at rest, immediately after the EVE and 3 minutes after the EVE. Venous blood samples were collected at rest, immediately after cessation of each EVE, and 1 h after each EVE. The results showed that the EVE significantly (p < 0.05) impaired CRT under N and H, and NCR under H only in the E group. The higher WRmax in the E compared to the S and C groups was associated with a significant (p < 0.005) increase in adrenaline (A) and noradrenaline (NA). There were no significant differences between conditions (N vs. H) in the BDNF at rest and after exercise. The EVE impaired cognitive function only in the E group; higher involvement of the sympathetic nervous system, A and NA may also play a role in this phenomenon. Therefore, it can be concluded that exposure to H did not have a negative impact on CRT or NCR. Moreover, BDNF did not improve cognitive function.

Myofascial Trigger Points therapy decreases myotonometric tone and stiffness of trapezius muscle, benefits headaches and muscle pain in migraine.

BACKGROUND: Migraine is a primary headache disorder. Studies have shown that 93% of people with migraine have an increased number of active Ischemic Compression Myofascial Trigger Points (IC-MTrPs) therapy. OBJECTIVE: To examine the effects of the IC-MTrPs therapy on: (1) mechanical properties of the upper trapezius muscle (UTM), (2) shoulder girdle and neck (SGN) muscles pain and (3) headaches characteristics in episodic migraine patients without aura. METHODS: Thirty-one adult, female, migraine patients without aura underwent seven IC-MTrPs therapy sessions and were tested during maximally five measurement sessions (pre- and post-1'st, post-4'th, post-7'th therapy and 1-month follow-up). Myotonometric measurements of the UTM's tone, stiffness and elasticity, subjective SGN muscles pain, as well as headache's level, frequency and duration were analyzed. RESULTS: Myotonometric tone and stiffness of the UTM significantly decreased in post-1'st, post-4'th therapy and in 1-month follow-up measurements versus pre-1'st therapy testing session. The scores for the SGN muscles' pain significantly decreased: (i) in post-4'th and post-7'th therapy versus post-1'st therapy session, and (ii) in post-7'th versus post-4'th therapy measurements. Headache's level, frequency and duration significantly decreased in post-7'th therapy versus pre-1'st therapy measurement session. CONCLUSION: IC-MTrPs therapy resulted in a decrease of upper trapezius muscle tone and stiffness, with simultaneous alleviation of shoulder girdle and neck muscle pain and the headaches characteristics in episodic migraine patients without aura.

High-intensity interval training modulates inflammatory response in Parkinson's disease.

BACKGROUND: Recent discoveries show that high-intensity interval training (HIIT) can bring many positive effects such as decreases in fat tissue, lower blood sugar levels, improved learning and memory, and lower risk of cardiac disease. Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of the dopaminergic neurons, accompanied by chronic inflammation and neuroinflammation. Previous research shows that interval training can bring a beneficial effect on the inflammation and neuroplasticity in PD. OBJECTIVES: The objective of this study was to investigate the effect of 12 weeks of HIIT on the inflammation levels and antioxidant capacity in the serum of PD patients. METHODS: Twenty-eight people diagnosed with PD were enrolled in this study. Fifteen PD patients performed 12 weeks of HIIT on a cycloergometer. Thirteen non-exercised PD patients constitute the control group. Concentrations of inflammation markers and antioxidants' capacity in the serum were measured at 3 sampling points (a week before, a week after, and 3 months after the HIIT). RESULTS: Twelve weeks of HIIT decreases the level of TNF-α (p = 0.034) and increases the level of IL-10 (p = 0.024). Those changes were accompanied by a decreased level of neutrophils (p = 0.03), neutrophil/lymphocyte ratio (p = 0.048) and neutrophil/monocyte ratio (p = 0.0049) with increases in superoxide dismutase levels (p = 0.04). CONCLUSIONS: Twelve weeks of HIIT can decrease systemic inflammation in PD patients and improve the antioxidant capacity in their serum, which can slow down the progression of the disease.

Serum metabolic profiles and metal levels of patients with multiple sclerosis and patients with neuromyelitis optica spectrum disorders - NMR spectroscopy and ICP-MS studies.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a disease misdiagnosed with multiple sclerosis (MS). We hypothesized that the serum metabolic profile could be helpful in the differentiation of both diseases in an early stage. METHODS: We included controls, patients with MS diagnosed according to the McDonald criteria of 2010, and patients with NMOSD diagnosed according to the criteria from 2015. Blood samples were collected on clots from all participants after overnight overfasting. We obtained metabolic profiles using proton magnetic resonance spectroscopy (1HNMR) of serum hydrophilic and hydrophobic compounds. Serum metal levels were measured using isotope-specific detection mass spectrometry (ICP-MS). For statistical analyzes, we used ANOVA tests and multivariate analysis (MVA) - orthogonal partial least square discriminant analysis (OPLS-DA). RESULTS: We analyzed metabolite levels in patient groups compared to controls. We observed significantly different levels of ten metabolite signals in patients with MS vs controls and eighteen metabolite signals in patients with NMSOD vs controls. We observed significantly different levels of five signals in patients with MS vs NMOSD. In the MVA analysis of patient groups, we indicated compounds that most differentiated the groups. All of these compounds are involved in cycles connected to the inflammation process and/or oxidative stress. The results of metallomics studies confirmed metal participation in these processes. DISCUSSION: It is possible to distinguish patients with MS and NMOSD from controls using ANOVA and MVA tests. The chosen metabolite profile analyzes might possibly be helpful in distinguishing the two diseases from each other in some seronegative and radiologically negative cases.

Effects of Short-Term Phosphate Loading on Aerobic Capacity under Acute Hypoxia in Cyclists: A Randomized, Placebo-Controlled, Crossover Study.

The aim of this study was to evaluate the effects of sodium phosphate (SP) supplementation on aerobic capacity in hypoxia. Twenty-four trained male cyclists received SP (50 mg·kg-1 of FFM/day) or placebo for six days in a randomized, crossover study, with a three-week washout period between supplementation phases. Before and after each supplementation phase, the subjects performed an incremental exercise test to exhaustion in hypoxia (FiO2 = 16%). Additionally, the levels of 2,3-diphosphoglycerate (2,3-DPG), hypoxia-inducible factor 1 alpha (HIF-1α), inorganic phosphate (Pi), calcium (Ca), parathyroid hormone (PTH) and acid-base balance were determined. The results showed that phosphate loading significantly increased the Pi level by 9.0%, whereas 2,3-DPG levels, hemoglobin oxygen affinity, buffering capacity and myocardial efficiency remained unchanged. The aerobic capacity in hypoxia was not improved following SP. Additionally, our data revealed high inter-individual variability in response to SP. Therefore, the participants were grouped as Responders and Non-Responders. In the Responders, a significant increase in aerobic performance in the range of 3-5% was observed. In conclusion, SP supplementation is not an ergogenic aid for aerobic capacity in hypoxia. However, in certain individuals, some benefits can be expected, but mainly in athletes with less training-induced central and/or peripheral adaptation.

Post-translational and post-transcriptional mechanisms of activity regulation of tyrosine hydroxylase in the central nervous system ­ the effect of physical exercise / Post-translacyjne i post-transkrypcyjne mechanizmy regulacji aktywnosci hydroksylazy tyrozynowej w osrodkowym ukladzie nerwowym-wplyw wysilku fizycznego.

Numerous studies indicate that dopamine (DA) is an important regulator of motor, psychological and cognitive functions. Maintaining the appropriate concentration of DA is a condition for the proper functioning of these functions. Tyrosine hydroxylase is involved in the control of DA synthesis. The aim of this study is to discuss the regulation of TH activity with the participation of three main mechanisms: 1) post-translational immediate regulation by phosphorylation of various sites in the enzyme molecule and 2) post-transcriptional with the participation of transcription factors and specific miRNAs, and 3) a DA mediated feedback mechanism. Important factors which are directly or indirectly involved in these regulations of TH activity and DA concentration are BDNF, testosterone, alpha-synuclein and protein kinases. A drastic reduction in DA levels in the extrapyramidal system causes drastic impairment of motor, psychological and cognitive functions. On the other hand, increased physical activity, in particular prolonged repetitive physical exercises by increasing the level of testosterone and BDNF in the blood, may activate signaling pathways dependent on them, increasing the activity of tyrosine hydroxylase, and thus increase the level of dopamine in the extrapyramidal system.

Red Blood Cell 2,3-Diphosphoglycerate Decreases in Response to a 30 km Time Trial Under Hypoxia in Cyclists.

Red blood cell 2,3-diphosphoglycerate (2,3-DPG) is one of the factors of rightward-shifted oxygen dissociation curves and decrease of Hb-O2 affinity. The reduction of Hb-O2 affinity is beneficial to O2 unloading at the tissue level. In the current literature, there are no studies about the changes in 2,3-DPG level following acute exercise in moderate hypoxia in athletes. For this reason, the aim of this study was to analyze the effect of prolonged intense exercise under normoxic and hypoxic conditions on 2,3-DPG level in cyclists. Fourteen male trained cyclists performed a simulation of a 30 km time trial (TT) in normoxia and normobaric hypoxia (FiO2 = 16.5%, ~2,000 m). During the TT, the following variables were measured: power, blood oxygen saturation (SpO2), and heart rate (HR). Before and immediately after exercise, the blood level of 2,3-DPG and acid-base equilibrium were determined. The results showed that the mean SpO2 during TT in hypoxia was 8% lower than in normoxia. The reduction of SpO2 in hypoxia resulted in a decrease of average power by 9.6% (p < 0.001) and an increase in the 30 km TT completion time by 3.8% (p < 0.01) compared to normoxia. The exercise in hypoxia caused a significant (p < 0.001) decrease in 2,3-DPG level by 17.6%. After exercise in normoxia, a downward trend of 2,3-DPG level was also observed, but this effect was not statistically significant. The analysis also revealed that changes of acid-base balance were significantly larger (p < 0.05) after exercise in hypoxia than in normoxia. In conclusion, intense exercise in hypoxic conditions leads to a decrease in 2,3-DPG concentration, primarily due to exercise-induced acidosis.

The Effect of Endurance Training on Brain-Derived Neurotrophic Factor and Inflammatory Markers in Healthy People and Parkinson's Disease. A Narrative Review.

Background: One purpose of the training conducted by people is to lose bodyweight and improve their physical condition. It is well-known that endurance training provides many positive changes in the body, not only those associated with current beauty standards. It also promotes biochemical changes such as a decreased inflammatory status, memory improvements through increased brain-derived neurotrophic factor levels, and reduced stress hormone levels. The positive effects of training may provide a novel solution for people with Parkinson's disease, as a way to reduce the inflammatory status and decrease neurodegeneration through stimulation of neuroplasticity and improved motor conditions. Aim: This narrative review aims to focus on the relationship between an acute bout of endurance exercise, endurance training (continuous and interval), brain-derived neurotrophic factor and inflammatory status in the three subject groups (young adults, older adult, and patients with Parkinson's disease), and to review the current state of knowledge about the possible causes of the differences in brain-derived neurotrophic factor and inflammatory status response to a bout of endurance exercise and endurance training. Furthermore, short practical recommendations for PD patients were formulated for improving the efficacy of the training process during rehabilitation. Methods: A narrative review was performed following an electronic search of the database PubMed/Medline and Web of Science for English-language articles between January 2010 and January 2020. Results: Analysis of the available publications with partial results revealed (1) a possible connection between the brain-derived neurotrophic factor level and inflammatory status, and (2) a more beneficial influence of endurance training compared with acute bouts of endurance exercise. Conclusion: Despite the lack of direct evidence, the results from studies show that endurance training may have a positive effect on inflammatory status and brain-derived neurotrophic factor levels. Introducing endurance training as part of the rehabilitation in Parkinson's disease might provide benefits for patients in addition to pharmacological therapy supplementation.

Role of brain-derived neurotrophic factor in appetite control / Rola neurotroficznego czynnika pochodzenia mózgowego w kontroli laknienia.

It has been found that in brain areas responsible for controlling appetite brain-derived neurotrophic factor (BDNF) and TrkB receptor expression are also present. In addition to involvement in neurogenesis, neuroprotection and synaptic plasticity, BDNF has anorexigenic activity. Decreasing of BDNF levels in the brain causes uncontrolled food intake, in turn, administration of BDNF to the central nervous system (CNS) leads to weight loss in animals. BDNF may participate with other factors such as leptin, insulin, cholecystokinin or corticotropin in the regulation of food intake. In addition, BDNF can affect glucose metabolism. It was found that peripheral BDNF level is lower in anorexia compared to healthy people. Moreover, BDNF levels tend to return to basal value when body weight normalizes. The mutation in the BDNF gene could also be important in the pathogenesis of obesity, although data on the blood concentration of this neurotrophin in obese are ambiguous.

Comparison of maximal lactate steady state with anaerobic threshold determined by various methods based on graded exercise test with 3-minute stages in elite cyclists.

BACKGROUND: The maximal lactate steady state (MLSS) is defined as the highest workload that can be maintained for a longer period of time without continued blood lactate (LA) accumulation. MLSS is one of the physiological indicators of aerobic performance. However, determination of MLSS requires the performance of a series of constant-intensity tests during multiple laboratory visits. Therefore, attempts are made to determine MLSS indirectly by means of anaerobic threshold (AT) evaluated during a single graded exercise test (GXT) until volitional exhaustion. The aim of our study was to verify whether AT determined by maximal deviation (Dmax), modified maximal deviation (ModDmax), baseline LA concentration + 1 mmol/l (+ 1 mmol/l), individual anaerobic threshold (IAT), onset of blood lactate accumulation (OBLA4mmol/l) and V-slope methods based on GXT with 3-min stages provide valid estimates of MLSS in elite cyclists. METHODS: Twelve elite male cyclists (71.3 ± 3.6 ml/kg/min) completed GXT (the increase by 40 W every 3 min) to establish the AT (by Dmax, ModDmax, + 1 mmol/l, IAT, OBLA4mmol/l and V-slope methods). Next, a series of 30-min constant-load tests to determine MLSS was performed. Agreement between the MLSS and workload (WR) at AT was evaluated using the Bland-Altman method. RESULTS: The analysis revealed a very high (rs > 0.90, p < 0.001) correlation between WRMLSS and WRDmax and WRIAT. The other AT methods were highly (rs > 0.70) correlated with MLSS except for OBLA4mmol/l (rs = 0.67). The Bland-Altman analysis revealed the highest agreement with MLSS for the Dmax, IAT and + 1 mmol/l methods. Mean difference between WRMLSS and WRDmax, WRIAT and WR+1mmol/l was 1.7 ± 3.9 W, 4.3 ± 7.9 W and 6.7 ± 17.2 W, respectively. Furthermore, the WRDmax and WRIAT had the lowest limits of agreement with the WRMLSS. The ModDmax and OBLA4mmol/l methods overestimated MLSS by 31.7 ± 18.5 W and 43.3 ± 17.8 W, respectively. The V-slope method underestimated MLSS by 36.2 ± 10.9 W. CONCLUSIONS: The AT determined by Dmax and IAT methods based on the cycling GXT with 3-min stages provides a high agreement with the MLSS in elite cyclists. Despite the high correlation with MLSS and low mean difference, the AT determined by + 1 mmol/l method may highly overestimate or underestimate MLSS in individual subjects. The individual MLSS cannot be properly estimated by V-slope, ModDmax and OBLA4mmol/l methods.

High-dose testosterone supplementation disturbs liver pro-oxidant/antioxidant balance and function in adolescent male Wistar rats undergoing moderate-intensity endurance training.

In some countries, anabolic-androgenic steroid abuse is rampant among adolescent boys and young men, including some of those seeking physical fitness and/or pleasing appearance through various exercise types. This tactic carries the risk of severe harmful health effects, including liver injury. Most anabolic-androgenic steroid stacking protocols employed are based on the use of the 'prototypic' anabolic-androgenic steroid testosterone and/or its esters. There is a vast body of data on the effects of anabolic-androgenic steroids' abuse combined with physical exercise training on the liver antioxidant barrier in adult subjects, whereas those concerning adolescents are scant. This study aimed to assess, in adolescent male Wistar rats undergoing a 6-week moderate-intensity endurance training (treadmill running), the influence of concurrent weekly supplementation with intramuscular testosterone enanthate (TE, 8 or 80 mg/kg body weight/week) on selected indices of liver status and oxidative stress. The rats were sacrificed, and their livers and blood samples were harvested two days after the last training session. High-dose TE treatment significantly reduced body and liver weight gains. Neither low-dose nor high-dose TE treatment affected liver α-tocopherol or γ-tocopherol content, whereas low-dose TE treatment significantly lowered hepatic reduced glutathione content. TE treatment significantly elevated liver thiobarbituric acid-reactive substances content and blood activities of alkaline phosphatase and γ-glutamyltransferase, but not of aspartate aminotransferase or alanine aminotransferase. Liver catalase activity was lowered by >50% in both TE-treated groups, while superoxide dismutase activity was significantly but slightly affected (-15%) only by the high-dose TE treatment. Glutathione peroxidase and glutathione reductase activities were not significantly altered. TE treatment significantly increased liver thiobarbituric acid-reactive substances content and lowered blood HDL-cholesterol, but did not significantly affect LDL-cholesterol or triglycerides level. In conclusion, high-dose TE treatment significantly disturbed liver antioxidant barrier and prooxidative-antioxidative balance and hence counteracted favorable effects of concurrent moderate-intensity endurance training in adolescent male rats.

Changes in the metabolic profiles of the serum and putamen in Parkinson's disease patients - In vitro and in vivo NMR spectroscopy studies.

The aim of this study was to investigate the relationship between serum metabolomic biomarkers and brain in vivo magnetic resonance spectroscopy (MRS) biomarkers in patients with Parkinson's disease (PD) as well as to investigate compound concentration changes by comparing the results with healthy control subjects. Univariate statistical analysis of the serum showed significant differences in the levels of phenylalanine, tyrosine, lysine, glutamine, glutamate, acetone, acetate, 3-hydroxybutyrate, and 1-monoacylglycerol (1-MAG) between the PD patient group and the control group. Orthogonal partial least squares discriminant analysis showed significantly different compound concentrations of acetate, 3-hydroxybutyrate, glutamine, tyrosine, 1-MAG and testosterone. In vivo MRS of the putamen showed significantly higher concentrations of glutamine/glutamate complex and glutamine in patients with PD in comparison to control subjects. Following disrupted metabolic pathways in patients with PD were identified: dopamine synthesis, steroid hormone biosynthesis, fatty acid biosynthesis, the synthesis and degradation of ketone bodies, the metabolism of pyruvate, arginine, proline, alanine, aspartate, glutamate, tyrosine and phenylalanine. The obtained results may indicate changes in neurotransmission, disturbances in energy production and an altered cell membrane structure.

Exercise-Induced Elevated BDNF Level Does Not Prevent Cognitive Impairment Due to Acute Exposure to Moderate Hypoxia in Well-Trained Athletes.

Exposure to acute hypoxia causes a detrimental effect on the brain which is also manifested by a decrease in the ability to perform psychomotor tasks. Conversely, brain-derived neurotrophic factor (BDNF), whose levels are elevated in response to exercise, is a well-known factor in improving cognitive function. Therefore, the aim of our study was to investigate whether the exercise under hypoxic conditions affects psychomotor performance. For this purpose, 11 healthy young athletes performed a graded cycloergometer exercise test to volitional exhaustion under normoxia and acute mild hypoxia (FiO2 = 14.7%). Before, immediately after exercise and after a period of recovery, choice reaction time (CRT) and number of correct reactions (NCR) in relation to changes in serum BDNF were examined. Additionally, other selected factors which may modify BDNF production, i.e., cortisol (C), nitrite, catecholamines (adrenalin-A, noradrenaline-NA, dopamine-DA, serotonin-5-HT) and endothelin-1 (ET-1), were also measured. Exercise in hypoxic conditions extended CRT by 13.8% (p < 0.01) and decreased NCR (by 11.5%) compared to rest (p < 0.05). During maximal workload, NCR was lower by 9% in hypoxia compared to normoxia (p < 0.05). BDNF increased immediately after exercise in normoxia (by 29.3%; p < 0.01), as well as in hypoxia (by 50.0%; p < 0.001). There were no differences in BDNF between normoxia and hypoxia. Considering the fact that similar levels of BDNF were seen in both conditions but cognitive performance was suppressed in hypoxia, acute elevation of BDNF did not compensate for hypoxia-induced cognition impairment. Moreover, neither potentially negative effects of C nor positive effects of A, DA and NO on the brain were observed in our study.

Gene polymorphisms and motor levodopa-induced complications in Parkinson's disease.

OBJECTIVE: The aim of the study was to evaluate the association of individual and combined single-nucleotide polymorphisms in brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT) genes with the occurrence of motor levodopa-induced complications (MLIC) in Parkinson's disease (PD). MATERIALS AND METHODS: We studied 76 patients with PD (MLIC occurred in 56.6%) and 60 controls. Allelic discrimination of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes were genotyped. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multinominal logistic regression. Orthogonal partial least squares (OPLS) analysis and OPLS discriminant analysis (OPLS-DA) were used to analyze qualitative genetic data. RESULTS: The risk of PD in subjects with the AG BDNF genotype was increased sixfold (OR = 6.12, 95% CI = 2.88-13.02, p < .0001), and AG BDNF and AG DAT genotypes were correlated with PD in OPLS-DA (VIP > 1). There were no differences in distributions of BDNF, DAT and COMT genotypes between PD groups with and without MLIC, while OPLS model showed that genotype combination of AG BDNF, AG DAT, and GG COMT was correlated with MLIC and genotypes combination of GG BDNF, AA DAT, and AA COMT with lack of MLIC in PD patients (VIP > 1). CONCLUSIONS: Our results confirmed the association of rs6265 BDNF (Val66Met) with the risk of PD and suggest a synergic effect of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) polymorphisms on the occurrence of MLIC.

BDNF as a Promising Therapeutic Agent in Parkinson's Disease.

Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson's disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient's brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD.

Intermittent Hypoxic Training at Lactate Threshold Intensity Improves Aiming Performance in Well-Trained Biathletes with Little Change of Cardiovascular Variables.

The main objective of this research was to evaluate the efficacy of intermittent hypoxic training (IHT) on aiming performance and aerobic capacity in biathletes. Fourteen male biathletes were randomly divided into a hypoxia group (H) (n = 7), which trained three times per week in a normobaric hypoxic environment (FiO2 = 16.5%, 2000 m a.s.l.) with lactate threshold intensity (LT) determined in hypoxia, and a control group (C) (n = 7), which exercised under normoxic conditions with LT intensity determined in normoxia. The training program included three weekly microcycles, followed by three days of recovery. The main part of the interval workout consisted of four 7 min (1st week), 8 min (2nd week), or 9 min (3rd week) running bouts at treadmill separated by 2 minutes of active recovery. After the warm-up and during the rest between the bouts, the athletes performed aiming to the target in the standing position with a sporting rifle (20 s). The results showed that the IHT caused a significant (p < 0.05) increase in retention time in the target at rest (RT9rest) by 14.4% in hypoxia, whereas RT postincremental test (RT9post) increased by 27.4% in normoxia and 26.7% in hypoxia. No significant changes in this variable were found in group C. Additionally, the capillary oxygen saturation at the end of the maximal effort (SO2capillary max) in hypoxia increased significantly (p < 0.001) by ∼4% after IHT. The maximal workload during the incremental test (WRmax) in normoxia also increased significantly (p < 0.001) by 6.3% after IHT. Furthermore, in absolute and relative values of VO2max in normoxia, there was a propensity (p < 0.07) for increasing this value by 5% in group H. In conclusion, the main findings of this study showed a significant improvement in resting and postexercise aiming performance in normoxia and hypoxia. Furthermore, the results demonstrated beneficial effects of the IHT protocol on aerobic capacity of biathletes.