Physical Exercise and Metabolism
Dr. Duygu Sen
PD Dr. Gerd Wagner
The brain orchestrates somatic, cognitive and social functions associated with internal and external stimuli via electrical and chemical neurotransmission, but also via a complex network of paracrine and endocrine signals that connects individual brain regions to the organ systems and to the whole body. Interactions between the brain regions, organs, and organ systems vary dynamically, allowing the same brain network structure or subsections of the brain network to be associated with many physiological and psychological states. The emerging functional complexity necessitates a well-tuned and efficient energy supply and intercellular communication. Following the increased energy demand induced by cellular or psychosocial stressors, mild dysfunctions in cellular bioenergetics and associated elements of intercellular communication may present itself with mental complaints even prior to full-blown manifestations of the somatic aspects especially.
For instance, common abnormalities are reported in cellular bioenergetics and immune response such as increased basal blood levels or endotoxin-induced production of pro-inflammatory cytokines in major depressive disorder (MDD) patients and in patients, who suffer from somatic disorders such as metabolic, cardiovascular and autoimmune diseases. Even though psychological and behavioral factors, such as the burden of being chronically ill or poor personal care, may provide alternatives to explain the bidirectional association between MDD and somatic disorders to some extent, some shared underlying pathological processes, such as chronic low-grade inflammation, deserve closer attention. Inflammatory mediators, which are also highly efficient elements of intracellular communication, interact with various steps of neurometabolism and body glucose metabolism. It has now been suggested that a particular subtype of MDD, namely atypical subtype, can be a manifestation of inefficient energy metabolism and associated chronic low-grade inflammation, which also manifests itself as metabolic disorders such as obesity or Type 2 Diabetes Mellitus.
Our group examines the effects of cellular and psychosocial stressors as well as antidepressant treatments on the brain and body interaction. By doing so, we aim to define MDD subgroups associated to immunometabolic disorders and bioenergetic dysfunction and to offer augmentative treatment options such as structured physical exerices programs by integrating multilevel evidence of behavioral, molecular and neuroimaging traits.
Physical exercise, indeed, is a powerful tool to prevent and to treat affective disorders. Evidences suggest its practice has a positive impact on cogitive functions, mostly on executive functions and attention. Also, the antidepressive effects of the exercise has been reported in many studies. While there is evidence for the association of physical exercise with brain structure, connectivity and metabolism, the neuronal and peripheral mechanisms of physical exercise remain unclear. Regular exercise seems to affect and normalize metabolites related to pathological cell turnover and neuroinflammation, which were associated with depressive states and cognitive impairments. We are therefore investigating whether changes in immunometabolism, cellular bioenergetics and brain activation patterns correspond to changes in cognition, mood and self-fatigue after structured physical exercise programs.
Karatas, H., Erdener, S.E., Gursoy-Ozdemir, Y., Lule, S., Eren-Kocak, E., Sen, Z.D., Dalkara, T., 2013. Spreading depression triggers headache by activating neuronal Panx1 channels. Science 339, 1092-1095.
Wagner, G., Herbsleb, M., Cruz, F., Schumann, A., Brunner, F., Schachtzabel, C., Gussew, A., Puta, C., Smesny, S., Gabriel, H.W., Reichenbach, J.R., Bar, K.J., 2015. Hippocampal structure, metabolism, and inflammatory response after a 6-week intense aerobic exercise in healthy young adults: a controlled trial. J Cereb Blood Flow Metab.
Wagner, G., Gussew, A., Kohler, S., de la Cruz, F., Smesny, S., Reichenbach, J.R., Bar, K.J., 2016. Resting state functional connectivity of the hippocampus along the anterior-posterior axis and its association with glutamatergic metabolism. Cortex 81, 104-117.
Bär, K.J., Herbsleb, M., Schumann, A., de la Cruz, F., Gabriel, H.W., Wagner, G., 2016. Hippocampal-Brainstem Connectivity Associated with Vagal Modulation after an Intense Exercise Intervention in Healthy Men. Frontiers in neuroscience 10, 145.
Wagner, G., Herbsleb, M., de la Cruz, F., Schumann, A., Kohler, S., Puta, C., Gabriel, H.W., Reichenbach, J.R., Bar, K.J., 2017. Changes in fMRI activation in anterior hippocampus and motor cortex during memory retrieval after an intense exercise intervention. Biological psychology 124, 65-78.
Colic, L., Woelfer, M., Colic, M., Leutritz, A.L., Liebe, T., Fensky, L., Sen, Z.D., Li, M., Hoffmann, J., Kretzschmar, M.A., Isermann, B., Walter, M., 2018. Delayed increase of thrombocyte levels after a single sub-anesthetic dose of ketamine - A randomized trial. Eur Neuropsychopharmacol 28, 701-709.
Sen, Z.D., Temucin, C.M., Basar, K., Ulug, B.D., Gokcen, O., Ozer, S., 2019. Alteration of the affective modulation of the startle reflex during antidepressant treatment. Psychophysiology 56.
Chand, T., Li, M., Jamalabadi, H., Wagner, G., Lord, A., Alizadeh, S., Danyeli, L.V., Herrmann, L., Walter, M., Sen, Z.D., 2020. Heart Rate Variability as an Index of Differential Brain Dynamics at Rest and After Acute Stress Induction. Frontiers in neuroscience 14.
Duygu Sen, Z., Vera Danyeli, L., Woelfer, M., Lamers, F., Wagner, G., Sobanski, T., Walter, M., 2020. Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: integrating the phenotypic, molecular and neuroanatomical dimensions. Brain Behav Immun.
Kurzweil, L., Danyeli, L., Sen, Z.D., Fejtova, A., Walter, M., Gensberger-Reigl, S., 2020. Targeted mass spectrometry of ketamine and its metabolites cis-6-hydroxynorketamine and norketamine in human blood serum. J Chromatogr B 1152.