Institute of Experimental Endocrinology

Understanding the effects of environment on the mental health of older adults is crucial in an aging society. Previous research concerning restorative benefits of forests almost entirely omitted older adults as the primary target group and typically involved group forest visits, which were largely restricted during the COVID-19 pandemic. Here we investigated the effects of individual walks on the mental health of adults aged 60 years or older (N = 54). A randomized parallel intervention study was conducted with one group walking in forests and the other in built-up city centres. Each participant completed eight individual 40-min walks during 1 month. Significant improvements in cognitive flexibility and heart rate variability (HRV) as an autonomic nervous system functioning indicator were established in the forest-walking group. The relationship between HRV and environment was modulated by ambient temperature. The study shows that access to forests during crises can support mental health of older adults as a vulnerable demographic.

Abstract BackgroundExercise improves physical fitness, cognitive functions & metabolism in the elderly. Evidence from animal models suggests the role for mediators from muscle or adipose tissue in the exercise‐induced brain plasticity (1). Knowledge on the regulation of these potentially neuroprotective molecules by exercise in humans is limited (2,3). We investigated effects of 3‐month supervised aerobic‐strength training on serum & cerebrospinal fluid/CSF adiponectin in the elderly, in association with cognitive functions & brain volumetry.MethodThe population consisted of sedentary elderly (n = 38, 10M/28F; 66.1±5.9yrs; BMI 26.3±3.7kg/m2). Body composition (MRI), physical fitness (Rockport test), muscle strength (dynamometry), motor tests (walking speed & chair stand tests), resting energy expenditure & substrate preference (REE, RQ, indirect calorimetry), insulin sensitivity & metabolic flexibility (euglycemic hyperinsulinemic clamp/EHC), cognitive functions (cognitive tests), brain volumetry (MRI), serum glucose & insulin were assessed.ResultTraining reduced BMI, blood pressure and insulinemia, while improving insulin sensitivity & metabolic flexibility (EHC), maximal aerobic capacity (VO2max), motor performance, and memory (ACE‐R). Improvements in cognitive functions were more pronounced in patients with MCI (p<0.05). Training led to a small but consistent increase of CSF adiponectin in cognitively healthy seniors (p<0.05), while no change was observed in MCI (p>0.1). CSF adiponectin was positively associated with psychomotor attention score (CogState), and it strongly correlated with the volume of corpus callosum normalized to intracranial volume. Training did not regulate serum adiponectin.ConclusionRelatively short‐term aerobic‐strength training can improve cognitive functions together with a spectrum of anthropometric, metabolic and fitness parameters, which may slow down the ageing‐related cognitive decline. Exercise modulated levels of adiponectin in CSF which correlated with cognitive functions and volume of specific brain areas. This might indirectly indicate the role for adiponectin in the exercise‐related brain plasticity in the elderly. Funding: APVV 20‐0466, VEGA‐2/0076/22, COST DePASS, APVV 15‐0253

IntroductionImpairment of bone structure in patients with acromegaly (AP) varies independently of bone mineral density (BMD). Body composition parameters, which are altered in patients with acromegaly, are important determinants of bone strength.PurposeThe aim of this study was to examine BMD and lumbar trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) and to assess its relationship with disease activity, age, glucose metabolism, and body composition parameters.MethodsThis cross-sectional prospective study involved 115 patients with acromegaly (70 F, 45 M) and 78 healthy controls (CON) (53 F, 25 M) matched for age, gender, and BMI. Bone mineral density, TBS and body composition parameters were measured using DXA.ResultsAP presented with lower TBS compared to CON (1.2 ± 0.1 v 1.31 ± 0.1, P< 0.001). No significant correlation was observed between IGF-1/GH levels and TBS. Age, glycated haemoglobin, BMI, waist circumference, fat mass, and lean mass negatively correlated with TBS in both sexes. Multiple linear regression analysis of all these parameters revealed age and waist circumference as independent significant predictors of TBS in AP. We did not find difference in BMD (lumbar and femoral sites) between AP and CON nor between active and controlled AP. We observed negative correlation between age and BMD of the femoral neck and total hip (P < 0.001). Testosterone levels in males, BMI, waist circumference, fat mass, and lean mass positively correlated with BMD in AP, with stronger correlation between lean mass and BMD compared to fat mass.ConclusionPatients with acromegaly have lower TBS than controls, confirming impaired bone microarchitecture in acromegaly regardless of BMD. Age, body composition parameters and glucose metabolism contribute to TBS deterioration in AP more than disease activity itself.

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 (5-HTTLPR), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.

Metabolomics has emerged as a powerful new tool in precision medicine. No studies have yet been published on the metabolomic changes in cerebrospinal fluid (CSF) produced by acute endurance exercise. CSF and plasma were collected from 19 young active adults (13 males and 6 females) before and 60min after a 90-min monitored outdoor run. The median age, BMI, and VO2 max of subjects was 25 years (IQR 22-31), 23.2kg/m2 (IQR 21.7-24.5), and 47 ml/kg/min (IQR 38-51), respectively. Targeted, broad-spectrum metabolomics was performed by liquid chromatography, tandem mass spectrometry (LC-MS/MS). In the CSF, purines and pyrimidines accounted for 32% of the metabolic impact after acute endurance exercise. Branch chain amino acids, amino acid neurotransmitters, fatty acid oxidation, phospholipids, and Krebs cycle metabolites traceable to mitochondrial function accounted for another 52% of the changes. A narrow but important channel of metabolic communication was identified between the brain and body by correlation network analysis. By comparing these results to previous work in experimental animal models, we found that over 80% of the changes in the CSF correlated with a cascade of mitochondrial and metabolic changes produced by ATP signaling. ATP is released as a co-neurotransmitter and neuromodulator at every synapse studied to date. By regulating brain mitochondrial function, ATP release was identified as an early step in the kinetic cascade of layered benefits produced by endurance exercise.

Ryanodine receptor channels at calcium release sites of cardiac myocytes operate on the principle of calcium-induced calcium release. In vitro experiments revealed competition of Ca2+ and Mg2+ in the activation of ryanodine receptors (RyRs) as well as inhibition of RyRs by Mg2+. The impact of RyR modulation by Mg2+ on calcium release is not well understood due to the technical limitations of in situ experiments. We turned instead to an in silico model of a calcium release site (CRS), based on a homotetrameric model of RyR gating with kinetic parameters determined from in vitro measurements. We inspected changes in the activity of the CRS model in response to a random opening of one of 20 realistically distributed RyRs, arising from Ca2+/Mg2+ interactions at RyR channels. Calcium release events (CREs) were simulated at a range of Mg2+-binding parameters at near-physiological Mg2+ and ATP concentrations. Facilitation of Mg2+ binding to the RyR activation site inhibited the formation of sparks and slowed down their activation. Impeding Mg-binding to the RyR activation site enhanced spark formation and speeded up their activation. Varying Mg2+ binding to the RyR inhibition site also dramatically affected calcium release events. Facilitation of Mg2+ binding to the RyR inhibition site reduced the amplitude, relative occurrence, and the time-to-end of sparks, and vice versa. The characteristics of CREs correlated dose-dependently with the effective coupling strength between RyRs, defined as a function of RyR vicinity, single-channel calcium current, and Mg-binding parameters of the RyR channels. These findings postulate the role of Mg2+ in calcium release as a negative modulator of the coupling strength among RyRs in a CRS, translating to damping of the positive feedback of the calcium-induced calcium-release mechanism.

Pathogenesis of cancer is a complex process influenced by multiple factors, including lifestyle and environment. The increased incidence of hormone-related cancers (breast, uterus, prostate) is supposed to be linked to the substantial exposure to environmental endocrine disruptors (EDs; dioxins, pesticides, polychlorinated biphenyls, bisphenols, phthalates, etc.). Such associations have been indicated by epidemiological studies; the data particularly support the link to developmental exposures to EDs. EDs can dysregulate hormone signaling and cell functions through multifaceted molecular and biochemical mechanisms, and experimental studies reveal possible mechanisms of their oncogenic effects. Specifically, since most of the EDs are xenoestrogens, the estrogenic modes of action are partially responsible for their roles in carcinogenesis. Moreover, epigenetic mechanisms are supposed to be involved in adverse effects of EDs on future generations. In addition to EDs, the impact of other chemicals (heavy metals, cigarette smoke components, ethanol) on the onset of cancer should not be underestimated. Obesity, a substantial health problem worldwide, is considered a significant lifestyle risk factor for the endocrine-related cancers. Adipose tissue can contribute to excessive estrogen supply in the body, and adipokines can interfere with signaling pathways involved in malignant cell transformation. Further, circadian disruptions caused by exposure to artificial light at night and shift work may affect carcinogenesis in hormone-related tissues. Although the precise contribution and the mechanisms involved in the actions of these factors to cancer are not completely elucidated, the research findings can help us better understand endocrine-related cancer risk factors and identify possible ways to reduce their impact.KeywordsRisk factorsBreast cancerProstate cancerEndocrine disruptorsChemical exposureObesity

Studies published in the last two decades have clearly demonstrated that the nervous system plays a significant role in carcinogenesis, the progression of cancer, and the development of metastases. These studies, combining oncological and neuroscientific approaches, created the basis for the emergence of a new field in oncology research, the so‐called “neurobiology of cancer.” The concept of the neurobiology of cancer is based on several facts: (a) psychosocial factors influence the incidence and progression of cancer diseases; (b) the nervous system affects DNA mutations and oncogene‐related signaling; (c) the nervous system modulates tumor‐related immune responses; (d) tumor tissues are innervated; (e) neurotransmitters released from nerves innervating tumor tissues affect tumor growth and metastasis; (f) alterations or modulation of nervous system activity affects the incidence and progression of cancers; (g) tumor tissue affects the nervous system. The aim of this review is to characterize the pillars that create the basis of cancer neurobiology, to describe recent research advances of the nervous system's role in cancer diseases, and to depict potential clinical implications for oncology.