decreased brain metabolism
(2014). doi: 10.1016/j.mehy.2016.09.022, Kelly, T., and Lieberman, D. Z. B., dela Peña, I. J., Kim, M., Sayson, L. V., et al. Summarizing the metabolic effects in the brain caused by the decreased synthesis of thyroid hormones, it seems that, similar to peripheral tissues, oxidative phosphorylation is reduced, since we observed decreased expression of complex II and V in the frontal cortex and decreased ETS (CII) capacity in both brain â¦ Cerebral blood flow comprises nearly 18% of cardiac output to generate 50 mL/100 g of brain tissue per minute. 5:82. doi: 10.3389/fendo.2014.00082, Nam, H., Clinton, S. M., Jackson, N. L., and Kerman, I. In summary, the obtained results suggested that in both the depression and hypothyroidism models, a reduction in glycolysis and in the connection between glycolysis and the Krebs cycle occurred, while the weakening of oxidative phosphorylation was mainly due to a lower level of thyroid hormones. It has been shown that animals of these strains have common genetic background but differ in their susceptibility to stress (Tizabi et al., 2012; Nam et al., 2014). doi: 10.1074/jbc.M114.570879, Loh, H. H., Lim, L. L., Yee, A., and Loh, H. S. (2019). Neuropsychopharmacol. Abnormalities of brain metabolism by FDG-PET were noted in some of the initial case reports of antiâNMDA receptor encephalitis, including report of occipital hypometabolism. However, in the WKY rats receiving PTU, a simultaneous decrease in pyruvate dehydrogenase levels and pyruvate levels suggested the weakening of the Krebs cycle by limiting both its substrate and the enzyme linking glycolysis with the Krebs cycle. Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Chronic mild stress induces widespread decreases in thyroid hormone α1 receptor mRNA levels in brain-Reversal by imipramine. Proc. All graphs were prepared using GraphPad Prism 8. These changes indicate that lower levels of pyruvate dehydrogenase in the frontal cortex can be partially compensated by an increase in its activity. (2009). Steroids 70, 450–454. The effects of strain and PTU treatment on the level of Mitofusin 2, UCP4, VDAC1, and HK1 in the mitochondria-enriched fraction of frontal cortex and hippocampus. In the frontal cortex, the level of pyruvate dehydrogenase was significantly lower only in the WKY rats receiving PTU than in the rats under control conditions (treatment effect: F1,35 = 8.13, p = 0.007) (Figure 7A), whereas in the hippocampus, the levels of this enzyme were not changed in any treatment group (Figure 7B). Body weight gains (g) were measured once a week. Data are presented as % of control of respiratory flux control ratios, corrected with residual oxygen consumption (ROX) and normalized to max ETS (after FCCP titrations). 8:109. doi: 10.3389/fnbeh.2014.00109. Overexpression of the thyroid hormone-responsive (THRSP) gene in the striatum leads to the development of inattentive-like phenotype in mice. (2008). In the frontal cortex, PTU (treatment effect: F1,33 = 15.72, p = 0.0004) increased leak state [L: LEAK (CI)] respiration in the presence of complex I substrates (malate and glutamate) in both strains (Figure 10A). In contrast to the cortex, in the hippocampus, there was no decrease in the level of pyruvate dehydrogenase; however, the increased PDK4 level suggested that the activity of this enzyme could have been decreased. iPLA(2)β(-/-) or iPLA(2)β(+/-) compared with iPLA(2)β(+/+) mice showed widespread and significant baseline reductions in k* and J(in) for DHA. UCP4 expression was diminished in the WKY rats treated with PTU compared with its expression in the Wistar rats (treatment effect: F1,31 = 5.35, p = 0.028) in the frontal cortex only. 47, 379–391. n = 7–10. The plasma concentration of triglycerides was diminished in the WKY rats compared with that in the Wistar rats (strain effect: F1,33 = 10.07, p = 0.03) and with those in both groups receiving PTU (treatment effect: F1,33 = 46.13, p = 0.003) (Figure 3D). (2017). doi: 10.1016/j.bbi.2013.12.013, Pilhatsch, M., Winter, C., Nordström, K., Vennström, B., Bauer, M., and Juckel, G. (2010). In our study, we used WKY rats as a model of depression since this strain exhibits lower levels of monoamines in the brain than control rats and exhibits behavioral and hormonal alterations resembling those of depression, including increased reactivity to stress. 69, 106–115. In accordance with other data, the WKY rats showed significantly more immobility behavior (strain effect: F1,36 = 98.95, p < 0.0001) and less climbing time (strain effect: F1,36 = 128.86, p < 0.0001) than the control Wistar rats, i.e., the WKY rats showed depression-like behavior (Figures 1B,C). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. In the Wistar rats, PTU administration significantly diminished the level of PDK2 compared with those in the control Wistar animals and in the WKY rats treated with PTU (Figures 8A,B). Insulin resistance was linked to decreased brain glucose metabolism and predicted worse memory function among late-middle-aged adults at risk for Alzheimerâs disease, researchers reported online July 27 in JAMA Neurology. In the hippocampus, the decreased pyruvate levels were accompanied by reduced lactate concentrations in the mitochondrial fractions of all treated animal groups compared to that of the control Wistar rats; moreover, in the model of depression with hypothyroidism, lactate concentrations in the hippocampus were also reduced in the cytosolic fraction, which was even more clear than in the case of the frontal cortex, indicating a decrease in glycolysis efficiency. Neurosci. Hypotheses 97, 16–21. In the frontal cortex in the hypothyroidism models but not in the depression model, reduced levels of pyruvate may be caused by the increased conversion of pyruvate to lactate. Some membranes were cut to allow simultaneous incubation with different antibodies. Lower rates of glycolysis and higher brain glucose levels correlated to more severe plaques and tangles found in the brains of people with the disease. 37, 406–424. 2008). doi: 10.1073/pnas.1108220109, Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., et al. 5:62. doi: 10.3389/fendo.2014.00062, Rezin, G. T., Cardoso, M. R., Gonçalves, C. L., Scaini, G., Fraga, D. B., Riegel, R. E., et al. doi: 10.1155/2012/590648, Horowitz, M. A., and Zunszain, P. A. Although hypothyroidism appears to be an important factor in the pathogenesis of depression, the impact of thyroid hormones on the bioenergetics of the adult brain is still poorly known. The bands from the left: Wistar, WKY, Wistar PTU, WKY PTU. The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats. Anal. (2016). Additionally, in agreement with previous data, the WKY rats showed short-term memory impairment and reduced weight gain. Endocrinol. Epub 2010 Apr 13. Is respiratory activity in the brain mitochondria responsive to thyroid hormone action? The results are expressed as the average fold change ± SEM. We examined markers of glycolysis, the Krebs cycle, and oxidative phosphorylation that were selected mainly on the basis of the results of our previous studies conducted in a prenatal stress animal model of depression (Detka et al., 2015; Głombik et al., 2018, 2020). interest analysis sim ilarly indicated post-fCT reductions in regional cerebral glu I. cose metabolism. All authors contributed to the article and approved the submitted version. Psychiatry 21, 229–236. Brain Res. A fluorimetric assay kit (BioVision, Milpitas, CA, United States) was used to measure the concentration of pyruvate in the cytosolic fraction isolated from the frontal cortex and hippocampus. On the other hand, vasoconstriction of the cerebral vasculature will decrease CBF by increasing the CVR. Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: behavioral, electrophysiological, and molecular studies. TRα1 presumably mediates most of the effects of TH, and some studies show that mutation of this receptor increases depressive and anxiety behaviors, evokes memory impairment, and reduces glucose utilization in the brain (Cheng, 2005; Vallortigara et al., 2009; Pilhatsch et al., 2010; Richard et al., 2017). J. Comp. The frontal cortex and hippocampus were selected for current study because they are the main structures affected in depressive disorders. Moreover, in a chronic mild stress model of depression, a decrease in TRα1 mRNA expression in the brain and its reversal by imipramine suggest that this receptor may play a role in stress-induced depressive behavior and in antidepressant action (Stein et al., 2009). The following thermal cycling conditions were used: 2 min at 50°C, 10 min at 95°C, followed by 40 cycles of 95°C for 15 s and 60°C for 1 min. (2014, August 12). Med. Interplay between peripheral and central inflammation in obesity-promoted disorders: the impact on synaptic mitochondrial functions. Editorial: “thyroid hormone in brain and brain cells.”. Total RNA was extracted from the frontal cortex and hippocampus using a Total RNA Mini kit (A&A Biotechnology, Gdynia, Poland), after which the RNA concentrations in the samples were measured using a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific, Waltham, MA, United States). Additionally, since the WKY rats are partially resistant to antidepressant drugs, these rats are considered to be a model of treatment-resistant depression. Brain. Comparing the metabolic changes, a greater reduction in the glycolysis process was observed in the hippocampus than in the frontal cortex; in contrast, the Krebs cycle was weakened only in the frontal cortex. The T3 level in the frontal cortex and hippocampus was measured using the ELISA assay described above. (2012). Although behavioral tests, including the Porsolt test, have been widely used to screen potential antidepressant drug effects, whether they can assess depression in rodents remains a matter of debate (Yu et al., 2015). (2002). NIH Psychoneuroendocrinology 94, 121–133. Cannabinoids decrease the metabolism of glucose in the brain by University of the Basque Country Cannabis creates a â¦ The results are expressed as the average fold change ± SEM (A–D) or as the mean ± SEM. After gentle resuspension of the pellet containing the mitochondria, the protein concentration was measured using the BCA method (Smith et al., 1985). The results obtained in the current research confirmed and extended the data showing the presence of hypothalamic–pituitary–thyroid (HPT) axis disturbance in WKY rats and indicated the possible causes of the weaker action of these hormones in the brain compared to their action in peripheral tissue. The data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher. Regarding complex V (ATP synthase), an impact of PTU was observed (treatment effect: F1,34 = 35.90, p < 0.0001); diminished levels of this complex were demonstrated in both the Wistar and WKY rats (Figure 9A). 21, 1–22. Moreover, WKY rats exhibit hormonal alterations characteristic of depression, including dysregulation of the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–thyroid (HPT) axes. Sci. Summarizing the metabolic effects in the brain caused by the decreased synthesis of thyroid hormones, it seems that, similar to peripheral tissues, oxidative phosphorylation is reduced, since we observed decreased expression of complex II and V in the frontal cortex and decreased ETS (CII) capacity in both brain structures examined. Biochim Biophys Acta. Selective vulnerability of the hippocampal pyramidal neurons to hypothyroidism in male and female rats. Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats. We also verified the hypothyroidism model by determining the plasma lipid levels. doi: 10.1007/s00213-015-4034-7, Willner, P., Gruca, P., Lason, M., Tota-Glowczyk, K., Litwa, E., Niemczyk, M., et al. Please enable it to take advantage of the complete set of features! The animal study was reviewed and approved by Local Ethics Committee in Kraków, Poland (permission no. Int. Antibodies in autoimmune thyroiditis affect glucose metabolism of anterior cingulate. However the metabolic brain patterns in these tauopathies are quite different. Pilhatsch, M., Schlagenhauf, F., Silverman, D., Berman, S., London, E. D., Martinez, D., et al. doi: 10.1016/j.jad.2008.12.010, Kolasa, M., Faron-Górecka, A., Kus̈mider, M., Szafran-Pilch, K., Solich, J., Zurawek, D., et al. We showed here that brain activity in the frontal and temporal lobes in both sexes decreased significantly with normal aging. But gaining and losing fat can change the way your brain regulates your body weight. This test is based on the spontaneous tendency of rats to spend more time exploring a novel object than a familiar object. : a critical re-evaluation. Psychopharmacology 232, 3473–3495. | In the frontal cortex, the level of PDK2 did not differ among any of the examined groups; however, in the hippocampus, a strain × PTU effect was observed (F1,30 = 6.04, p = 0.020). Figure 9. Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death. It is also unresolved why in many animal models of depression based on stress procedures, not all animals develop depression-like behavioral changes despite the use of identical stressors, whereas the biochemical changes are most often similar (Kolasa et al., 2014). Then weâll talk about whether the metabolism can actually be damaged. (2014). Neuronal expression of a thyroid hormone receptor α mutation alters mouse behaviour. 9-methyl-β-carboline has restorative effects in an animal model of Parkinson’s disease. doi: 10.3892/mmr.2014.2825, Wernicke, C., Hellmann, J., Ziȩba, B., Kuter, K., Ossowska, K., Frenzel, M., et al. The first limitation is that only two behavioral tests were performed: the forced swim test and the novel object recognition test. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group. The results are expressed as the mean ± SEM. Weight gain was significantly lower in the WKY rats than in the Wistar rats, and PTU significantly reduced this parameter in both strains (Figure 1A). Rep. 70, 322–330. 53, 395–400. (2019). However, it should be taken into account that both impaired synaptic plasticity, which is considered crucial in the pathogenesis of depression, and hypothyroidism-induced disturbances in mitochondrial function can be caused by many factors, e.g., elevated glucocorticoid levels or a high-fat diet (HFD). Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+. Significant differences in TRα1 expression in the frontal cortex were observed between the rat strains (strain effect: F1,35 = 4.50, p = 0.041), but no effect of PTU was observed. Thus, increased THRSP expression in the hippocampus of WKY rats could be connected with the disturbances in synaptic plasticity demonstrated in this rat strain (Aleksandrova et al., 2019). 46/2018 of 01.02.2018). The concept that tissue-specific changes in thyroid hormone action may occur in depression even with normal thyroid hormone concentrations in the blood and pituitary gland was confirmed by data, indicating that treatment with high doses of thyroid hormones is well tolerated in patients with depression but not in healthy people (Kelly and Lieberman, 2009; Kelly, 2016). This is likely because the concentration of active thyroid hormone T3 in the brain depends not only on its synthesis in the thyroid gland but also, to a large extent, on the expression of transporters and deiodinase enzymes in particular brain structures (Flamant et al., 2015). doi: 10.1007/s12640-019-00131-w, Głombik, K., Ślusarczyk, J., Trojan, E., Chamera, K., Budziszewska, B., Lasoń, W., et al. In the frontal cortex, there were no differences in Thrsp expression between the strains or between the PTU administration and control groups (Figure 5E), but in the hippocampus, the mRNA level of Thrsp was significantly higher in the WKY rats than in the Wistar rats (strain effect: F1,34 = 7.11, p = 0.011), and PTU decreased this parameter in the WKY rats (treatment effect: F1,34 = 7.07, p = 0.011) (Figure 5F). Based on the findings, "midlife may be a critical period for initiating treatments aimed at preventing or delaying the onset of â¦ Clipboard, Search History, and several other advanced features are temporarily unavailable. DIO3 was significantly decreased in the WKY rats by PTU treatment (treatment effect: F1,32 = 11.17, p = 0.002), but there were no differences between the strains (Figure 5C). The concentrations of the examined proteins in the samples were calculated from a standard curve and are expressed as ng/mg protein for pyruvate dehydrogenase and as pg/mg protein for PDK2 and PDK4. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group. J. Biol. The effects of strain and PTU treatment on the pyruvate dehydrogenase level (A,B) and aconitase activity (C,D) in the mitochondria-enriched fraction of the frontal cortex and hippocampus. Pharmacol. Front. Measurement of protein using bicinchoninic acid. Med. Differences were considered significant at p < 0.05. Yassine HN, Croteau E, Rawat V, Hibbeln JR, Rapoport SI, Cunnane SC, Umhau JC. Some existing data indicate that hypothyroidism induces the detachment of hexokinase 1 (HK1) from the outer mitochondrial membrane by lowering the expression of voltage-dependent anion channel 1 (VDAC1), and this action may be an important cause of the disrupted coordination between glycolysis and oxidative phosphorylation (Regenold et al., 2012). Neuroscience 390, 141–150. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo SI, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T, Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N. Proc Natl Acad Sci U S A. 2017 Mar 23;9(1):23. doi: 10.1186/s13195-017-0250-1. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group. Psychiatry 63, 1127–1134. All experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Local Ethics Committee in Kraków, Poland (permission no. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group. The plasma concentrations of TSH (Demeditec, Kiel, Germany), free T3 and free T4 (both: DiaMetra, Perugia, Spello, Italy) were assayed using ELISA according to the instructions provided by the manufacturer. High-resolution respirometry (HRR) was used to measure mitochondrial respiration in both selected brain structures. The effects of TH depend mainly on the expression of specific isoforms of TH receptors and their dimerization with RXR. WKY rats were also characterized as a strain with increased reactivity to stress, prolonged ACTH and corticosterone secretion, and weakened negative feedback mechanisms (Aleksandrova et al., 2019). It is located in the head, usually close to the sensory organs for senses such as vision.It is the most complex organ in a vertebrate's body. n = 7–10. A decrease in glycolysis was evidenced by the finding that the level of pyruvate, the end product of glycolysis, was lower in both brain structures studied in the WKY rats than in the Wistar rats; additionally, the level of pyruvate was lower in both strains with hypothyroidism than in the strains under control conditions. 2011 Nov;96(1-4):109-13. doi: 10.1016/j.prostaglandins.2011.06.003. The ratio of the intensity of the target protein band to that of β-actin was used to compare target protein abundance in different samples. However, the action of thyroid hormones in BAT is relatively well studied, and it is known that T3 increases fatty acid oxidation and mitochondrial respiration and also affects the processes of mitophagy and biogenesis. J. Pharmacol. Figure 1. Although the vast majority of people with depression do not exhibit hypothyroidism, abnormal T4 to T3 ratios, elevated reverse T3 (rT3) levels, blunted TSH responses to TRH, and the presence of antithyroid antibodies are reported to be more common in people with depression than in the general population (Hage and Azar, 2012; Pilhatsch et al., 2014). The T3 levels in the brain were diminished by PTU (treatment effect: F1,32 = 21.06, p < 0.0001 for the frontal cortex; F1,32 = 16.09, p = 0.0003 for the hippocampus) in both strains and both brain areas (Figures 2E,F). doi: 10.1002/cne.903220405, Martorell-Riera, A., Segarra-Mondejar, M., Muñoz, J. P., Ginet, V., Olloquequi, J., Pérez-Clausell, J., et al. A., Jensen, J. E., Fava, M., and Renshaw, P. F. (2008). | Aconitase activity was calculated from a standard curve and is expressed as mU/mg protein. Animals were randomly assigned to four groups, each containing 10 animals: group I, control, Wistar rats fed a standard diet and drinking water ad libitum; group II, endogenous depression, WKY rats fed a standard diet and drinking water ad libitum; group III, hypothyroid, Wistar rats fed a standard diet and treated with 0.05% (w/v) propylthiouracil (PTU) in drinking water for 3 weeks; and group IV, coexistent depression and hypothyroidism, WKY rats fed a standard diet treated with 0.05% (w/v) PTU in drinking water for 3 weeks. Rep. 11, 775–782. (2015). Aconitase activity was measured in mitochondria-enriched fractions derived from both examined brain structures using an Aconitase Activity Colorimetric Assay Kit (BioVision, Milpitas, CA, United States) according to the manufacturer’s instructions. Results: Widespread regions of decreased regional cerebral glucose metabolism were identified after ECT, especially in the frontal and parietal cortex, anterior and posterior cingulate gy-rus, and left temporal cortex. Thyroid hormone responsive protein (THRP) mediates thyroid hormone-induced cytotoxicity in primary neuronal cultures. The level of LDL was increased in the WKY rats compared with that of the Wistar rats (strain effect: F1,33 = 10.22, p = 0.003) and with those of both strains after PTU administration (treatment effect: F1,33 = 131.05, p < 0.0001) (Figure 3C). Mitochondrial proteomics investigation of frontal cortex in an animal model of depression: focus on chronic antidepressant drugs treatment. Finally, the physiological importance of the reduced level of the gliotransmitter lactate and the increased expression of cytotoxic THRSP in the hippocampus in the model of depression used in this study should be determined in further studies. Additionally, changes in oxidative phosphorylation were present mainly in the frontal cortex, but these disturbances were related to a deficiency of thyroid hormones rather than depression. After completing this journal-based SA-CME activity, participants will be able to: 1. â Describe the process of neuronal uptake and cerebral biodistribution of FDG and identify normal cortical and subcortical structures at FDG PET. The forced swim test as a model of depressive-like behavior. Decreased thyroid hormone action was also shown to attenuate oxidative phosphorylation, and this change was greater in the WKY rats. Thyroid hormone signaling and adult neurogenesis in mammals. (2010). Another significant limitation of the current research is the use of only male rats, which did not allow us to determine the sex-related differences in the parameters tested. It is known that the proper function of mitochondria depends on maintaining a balance between fusion and fission. J. The corticosterone concentrations were measured by using an ELISA method with a commercially available assay kit (Fine Test, Wuhan, China) and are displayed as ng/ml. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the â¦ The results are expressed as the average fold change ± SEM (A–D) or as the mean ± SEM. The NOR test is a memory test that estimates the ability of rodents to recognize a novel object in the environment and is designed to assess recognition memory (Antunes and Biala, 2012). The lactate concentration in the mitochondrial fraction of the frontal cortex did not differ between the tested rat strains and was not changed in the animals that received PTU. Our study has some limitations. Front. J. Physiol. (2014). (2014). doi: 10.1055/s-2007-978852, Porsolt, R. D., Anton, G., Blavet, N., and Jalfre, M. (1978). After 1 h of blocking in 5% non-fat milk [in PBST with 0.05% Tween 20 (Sigma-Aldrich, Saint Louis, MO, United States)], membranes were incubated overnight with Total OXPHOS Rodent WB Antibody Cocktail (6.0 μg/mL, Abcam, Cambridge, United Kingdom) and UCP4 polyclonal (1.0 μg/mL, Thermo Fisher Scientific, Waltham, MA, United States), Mitofusin 2 monoclonal (1.0 μg/mL, Abcam, Cambridge, United Kingdom), VDAC1 monoclonal (1.0 μg/mL, Abcam, Cambridge, United Kingdom), or HK1 polyclonal (1:1000, Proteintech, Wuhan, China) antibodies diluted using a SignalBoost Immunoreaction Enhancer Kit (Merck, Darmstadt, Germany). The effects of strain and PTU treatment on the mitochondrial respiration of isolated mitochondria in the frontal cortex: leak state (A), OXHPOS (CI) capacity state (B), ETS (CI + CII) capacity state (C), ETS (CII) capacity state (D), ETS—coupling efficiency state (E), and OXPHOS—coupling efficiency state (F). How to Fix a Slow Metabolism Consume Foods that Increase Metabolism:. To understand this answer letâs explore how human metabolism actually works. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group; Λ vs. the Wistar PTU group. Neuroscience 213, 72–80. COVID-19 is an emerging, rapidly evolving situation. doi: 10.1016/j.steroids.2005.02.003, Crispino, M., Trinchese, G., Penna, E., Cimmino, F., Catapano, A., Villano, I., et al. Neurosci. Get the latest research from NIH: https://www.nih.gov/coronavirus. Cerebral metabolism is highly active and requires 20% of the body's oxygen while representing only 2% of a person's total body weight. The total T4 hormone levels were slightly but not significantly lower in WKY rats than in Wistar rats in the Redei study (Redei et al., 2001), while we found that the level of the free form of this hormone was significantly lower in the WKY rats than in the Wistar rats. After a 45-min incubation period and the addition of 10 μL of Developer to each well, the absorbance was measured at a wavelength of λ = 450 nm using a spectrophotometer (Tecan Infinite M200 Pro, Männedorf, Switzerland). In the hippocampus, the concentration of PDK4 was upregulated by administration of PTU (treatment effect: F1,32 = 10.39, p = 0.003) in the WKY rats. KG: methodology and visualization. The results are expressed as the average fold change ± SEM. The use of triiodothyronine as an augmentation agent in treatment-resistant bipolar II and bipolar disorder NOS. Alterations in markers that determine the effect of thyroid hormones in the frontal cortex clearly indicated that in the studied model of depression, their function could be weakened (as shown by the decreases in T3, TRα1, and DIO2), while in the hippocampus, only a downward trend in the T3 level was observed, while the changes in TRβ1, RXRα, and DIO3 suggested the induction of compensatory mechanisms for enhancing T3 action. Regul. lactate (CMR lact)]. Validation of chronic mild stress in the Wistar-Kyoto rat as an animal model of treatment-resistant depression. *Correspondence: Katarzyna Głombik, email@example.com, Front. Verification code: 0B79-790B-EB7D-2268-5D0B. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, Autoradiographs of coronal brain sections showing effects of arecoline and iPLA. Our results suggest that both the depression and hypothyroidism models are characterized by similar impairments in brain energy metabolism and mitochondrial function and, additionally, that the co-occurrence of hypothyroidism and depression may exacerbate some of the metabolic changes observed in depression. Antidepressant-Like effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in...., Y. T., and Howland, J. E., Fava, M. ( 1978 ) ( 2002.. Knockin mutant mice age in males were shown with an increased glucose metabolism in bipolar depression: on! Alpha 1 the manuscript has been edited by the authors, without reservation..., most studies indicate that thyroid hormones on mitochondrial function in adult brain 2-3 ):154-71.:... Y, McCammon JA, Dennis EA the level or activity of thyroid hormone brain. Transcription through nuclear TH receptors of mitofusin 2 between the WKY and Wistar rats ;! 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