However, the co-occurrence of hypothyroidism and depression led to changes in the presence or abundance of some metabolic markers, such as decreased pyruvate dehydrogenase levels in the frontal cortex, decreased lactate levels in the cytosolic fraction of the hippocampus, increased PDK4 expression in the hippocampus, and decreased ETS and OXPHOS coupling efficiency. The results are expressed as the mean ± SEM. doi: 10.1016/0003-2697(85)90442-7, Solberg, L. C., Olson, S. L., Turek, F. W., and Redei, E. (2001). Additionally, concerning hypothyroidism, some studies found an increase in depression-like behavior in rats, but others found decreased depression-like behavior (Yu et al., 2015). doi: 10.1097/FBP.0000000000000431, Yankelevitch-Yahav, R., Franko, M., Huly, A., and Doron, R. (2015). (2014). … The intensification of the leak state in animals with hypothyroidism could indicate the uncoupling of oxidative phosphorylation from ATP synthesis in these animals. doi: 10.1007/s12640-019-00131-w, Głombik, K., Ślusarczyk, J., Trojan, E., Chamera, K., Budziszewska, B., Lasoń, W., et al. 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). The covariance pattern of PSP consists of decreased metabolism in the prefrontal cortex, frontal eye fields, caudate nuclei, medial thalamus and upper brainstem (Eckert, et al. The manuscript has been edited by the American Journal Experts for proper English language, grammar, punctuation, spelling, and overall style. Med. PET measures emissions from radioactively labeled metabolically active chemicals that have been injected into … In addition, a mitochondrial respiration assay showed that PTU decreased ETS and OXPHOS coupling efficiency in the brain (ETS: F1,35 = 5.21 for the hippocampus, p = 0.0286; OXPHOS: treatment effect: F1,36 = 5.16 for the frontal cortex, p = 0.029; F1,35 = 5.17 for the hippocampus, p = 0.029), while the post hoc tests showed a significant decrease in ETS and OXPHOS coupling efficiency only in the hippocampus of the WKY rats after PTU administration and in OXPHOS coupling efficiency in the frontal cortex in the same group of animals (Figures 10F, 11E,F). We also verified the hypothyroidism model by determining the plasma lipid levels. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group. 2020 Feb;61(2):143-158. doi: 10.1194/jlr.RA119000281. Please enable it to take advantage of the complete set of features! 38, 365–377. Neurosci., 04 December 2020 Br J Pharmacol. *Correspondence: Katarzyna Głombik, [email protected], Front. Behav. Biochem. (2015). Additionally, we found that the uncoupling of oxidative phosphorylation from ATP synthesis did not result from the overexpression of uncoupling protein 4 (UCP4). After centrifugation (3,000 rpm, 20 min, 4°C), the separated plasma was collected and frozen at −20°C. 2017 Mar 23;9(1):23. doi: 10.1186/s13195-017-0250-1. J. 2019 Oct 8;116(41):20689-20699. doi: 10.1073/pnas.1902958116. N. Y. Acad. The results are expressed as the average fold change ± SEM. Behav. The next day, after rinsing 3 × 10 min with PBS with 0.05% Tween 20, the blots were incubated for 1 h at RT with either a horse anti-mouse or goat anti-rabbit IgG HRP-conjugated secondary antibody (Vector Laboratories, Peterborough, United Kingdom), washed 4 × 10 min in TBST (Tris-buffered saline with 0.05% Tween 20), and developed using the BM Chemiluminescence Western Blotting Substrate (POD) (Roche, Mannheim, Germany). It is difficult to explain that in contrast to our predictions, the administration of PTU did not lead to prolonged immobility time in the Porsolt test in either the Wistar or WKY rats. doi: 10.1016/0014-2999(78)90118-8, Ramsden, D. B., Ho, P. W. L., Ho, J. W. M., Liu, H. F., So, D. H. F., Tse, H. M., et al. Editorial: “thyroid hormone in brain and brain cells.”. doi: 10.1038/sj.mp.4000963, Cheng, S. (2005). KG and BB: conceptualization, writing—original draft, and writing—review. Years later, in 1897, British psychiatrist Henr… Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. (2015). There was no difference in the level of lactate in the cytosol in either the frontal cortex or hippocampus of the WKY and Wistar rats. Arecoline increased both parameters in brain regions of iPLA(2)β(+/+) mice but quantitatively less so in iPLA(2)β(-/-) and iPLA(2)β(+/-) mice. 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). Statistical evaluations were performed using the Statistica 13.3 software and consisted of two-way analyses of variance (ANOVA) followed by the Duncan post hoc test. The administration of PTU had no effect on immobility or climbing time but attenuated the memory impairment of the WKY rats and intensified the decrease in weight gain. 21, 1–22. For this reason, we compared the selected metabolic parameters in the WKY rats and the control Wistar rats under basal conditions and under conditions of decreased thyroid hormone synthesis (obtained by the administration of a thyroid peroxidase inhibitor). 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). n = 7–10. 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).  |  Similar to TRβ1, RXRα expression was higher in the WKY rats than in the Wistar rats (strain effect: F1,33 = 4.76, p = 0.036), and PTU increased its expression (treatment effect: F1,33 = 9.09, p = 0.005) in the Wistar rats only (Figure 4F). It is known that the proper function of mitochondria depends on maintaining a balance between fusion and fission. A total of 50 μL/well of reaction mix (42 μL of assay buffer, 2 μL of substrate, and 6 μL of enzyme mix) was added to each test sample and standard. These changes might contribute to reported altered behavior following early SSRI … The findings indicate a decrease in glycolysis intensity in both brain structures in the WKY rats as well as in both strains under hypothyroidism conditions. 2015, 1–7. Behav. The level of lactate in the samples was measured with a colorimetric assay kit (BioVision, Milpitas, CA, United States). Chem. This site needs JavaScript to work properly. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group. Psychiatry 63, 1127–1134. In our study, the levels of VDAC1 in the mitochondrial fraction in both brain structures examined did not change, and the HK1 concentration did not decrease or even increased in the hippocampus of the WKY rats treated with PTU; therefore, we excluded the participation of this mechanism in the models we examined. Figure 4. Significant differences between the rat strains (F1,34 = 6.53, p = 0.015), but no effect of PTU, was observed in DIO2 expression in the frontal cortex. Neuropsychopharmacol. Cerebral metabolic rate. A region-of-interest analysis similarly indicated post-ECT reductions in regional cerebral glucose … The concentration of lactate in each sample was calculated from the standard curve and is displayed as nmol/mg protein. The protein concentration in tissue homogenates was measured with the bicinchoninic acid method (Smith et al., 1985) using a PierceTM BCA Protein Assay Kit (Thermo Fisher Scientific, Waltham, MA, United States). Additionally, the level of PDK4 in PTU-treated animals was increased in the WKY rats compared with that in the Wistar rats (strain × treatment interaction F1,32 = 24.15, p < 0.0001) (Figure 8D). Endocrinol. Nat. J. Pharmacol. How to Fix a Slow Metabolism Consume Foods that Increase Metabolism:. Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. The ETS-coupling efficiency and OXPHOS-coupling efficiency were calculated based on the obtained data according to the following equations: ETS-coupling efficiency = (ETS capacity − LEAK respiration)/ETS; OXPHOS-coupling efficiency = (OXPHOS capacity − LEAK respiration)/OXPHOS. 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). Regulation of insulin receptor phosphorylation in the brains of prenatally stressed rats: new insight into the benefits of antidepressant drug treatment. KG: methodology and visualization. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group; Λ vs. the Wistar PTU group. After a 30-min incubation, the absorbance was measured at a wavelength of λ = 570 nm using a spectrophotometer (Tecan Infinite M200 Pro, Männedorf, Switzerland). doi: 10.1016/j.bbr.2016.12.025, Sebastian, D., Hernandez-Alvarez, M. I., Segales, J., Sorianello, E., Munoz, J. P., Sala, D., et al. It Can Cause Fatigue and Nutrient Deficiencies. 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. However the metabolic brain patterns in these tauopathies are quite different. Peptides 61, 98–106. 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. Since disturbances in mitochondrial respiration were demonstrated in both depression and hypothyroidism in the present study, the expression of oxidative phosphorylation complexes and mitochondrial activity in the various stages of respiration were analyzed in mitochondrial fractions isolated from the frontal cortex and hippocampus. 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. Pharmacol. Brain Res. Additionally, since the WKY rats are partially resistant to antidepressant drugs, these rats are considered to be a model of treatment-resistant depression. 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. Then we’ll talk about whether the metabolism can actually be damaged. *p < 0.05 vs. the control group (Wistar rats); #p < 0.05 vs. the WKY group. The novel object recognition memory: neurobiology, test procedure, and its modifications. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in … Eur. Integr. Thus, the increase in oxygen consumption in the leak state in animals receiving PTU suggested that in the rats with hypothyroidism, the inner mitochondrial membrane was more permeable to protons, and consequently, oxidative phosphorylation may have become uncoupled from ATP synthesis. Aleksandrova, L. R., Wang, Y. T., and Phillips, A. G. (2019). 116, 222–226. 2 supply to brain energy metabolism? In the frontal cortex, the decreased expression of complex II and complex V in rats with hypothyroidism suggested that in this brain structure, not only glycolysis but also oxidative phosphorylation could be reduced. Brain Behav. doi: 10.1210/endo.143.5.8770, Popović, L., Orešković, K., Županèić, B., Petrunić, M., and Kunec-Vajić, E. (1998). KG, JD, and BB: formal analysis. PTU is an antithyroid drug which inhibits synthesis of thyroid hormones, used in the therapy of hyperthyroidism and Graves disease. Since depression is a highly heterogeneous disorder with diverse pathogenic origins, the lack of changes in depression-like behavior does not exclude the participation of other factors, including hypothyroidism, that do not affect the time of immobility but affect other processes (e.g., cause metabolic disturbances) in the pathogenesis of this disorder. 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 … 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. 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. interest analysis sim­ ilarly indicated post-fCT reductions in regional cerebral glu­ I. cose metabolism. This research was funded by Grant No. The forced swim test as a model of depressive-like behavior. Table 1. It is estimated that only approximately 20% of brain T3 is derived from the blood, and the majority is formed in glial cells from thyroxine under the action of DIO2 (Morte and Bernal, 2014). Proc. Cerebral blood flow comprises nearly 18% of cardiac output to generate 50 mL/100 g of brain tissue per minute. 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. Figure 2. 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). PTU had no effect on the activity of this enzyme in the frontal cortex but significantly enhanced hippocampal aconitase activity in both the Wistar and WKY rats (treatment effect: F1,32 = 77.62, p < 0.0001) (Figures 7C,D). •Brain represents 2 to 3% of total body weight of an average adult, but utilizes 20 to 25% of the total Oxygen consumed by the whole organism; •In children up to 4 years of age, the brain utilizes about 50% of the total Oxygen consumed by the whole organism; Behav. In contrast to the HPA axis, few data are available on HPT axis disturbances in these rats; however, higher plasma concentrations of T3 and TSH were found in the WKY rats than in the Wistar rats (Solberg et al., 2001). Decline in daily functioning related to decreased brain activity in Alzheimer's. In addition, the decreased metabolism in the frontal cortex in depression may result from decreases in the levels of T3 and TRα1 and in the expression of DIO2, an enzyme that catalyzes the conversion of T4 to the active T3 hormone. Tissue homogenates were centrifuged at 1,300 rpm for 10 min at 4°C. RESULTS: Widespread regions of decreased regional cerebral glucose metabolism were identified after ECT, especially in the frontal and parietal cortex, anterior and posterior cingulate gyrus, and left temporal cortex. 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). Affect. Aconitase activity was calculated from a standard curve and is expressed as mU/mg protein. 321, 18–27. doi: 10.1016/j.neubiorev.2019.07.007, PubMed Abstract | CrossRef Full Text | Google Scholar, Alzoubi, K. H., Gerges, N. Z., Aleisa, A. M., and Alkadhi, K. A. For these reasons, this strain, which is endogenously susceptible to stress, is an established genetic model of depression and is the most suitable control group in the context of depression studies in Wistar rats. 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 H 2O) on glucose metabolism in the human brain. The Ct values for each sample were measured in the exponential phase of the PCR, and the ΔΔCt method was used for data analysis. doi: 10.1016/j.jpsychires.2011.09.018, Remaud, S., Gothié, J.-D., Morvan-Dubois, G., and Demeneix, B. Neuroimmune and neuroendocrine abnormalities in depression: two sides of the same coin. The reduced level of growth factors in an animal model of depression is accompanied by regulated necrosis in the frontal cortex but not in the hippocampus. Int. Additionally, functional assays of mitochondrial respiration showed the impact of PTU, but not of strain, on the leak and OXPHOS states. Pharmacol. Cerebral metabolism is highly active and requires 20% of the body's oxygen while representing only 2% of a person's total body weight. (2014). (2010). 289, 31014–31028. 5:82. doi: 10.3389/fendo.2014.00082, Nam, H., Clinton, S. M., Jackson, N. L., and Kerman, I. Factorial ANOVA showed the effects of strain (F1,36 = 81.43, p < 0.0001) and PTU (F1,36 = 502.05, p < 0.0001) on weight gain over 3 weeks. The effects of strain and PTU treatment on the mitochondrial respiration of isolated mitochondria in the hippocampus: 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). Are Wistar-Kyoto rats a genetic animal model of depression resistant to antidepressants? The low efficacy of pharmacotherapy is probably because the antidepressant drugs currently in use mainly affect noradrenergic and serotonergic neurotransmission, while many studies have shown that this disease involves not only disturbances in neurotransmission but also changes in hormonal systems, immune systems, and energy processes that together impair synaptic plasticity, leading to numerous functional changes, including depressed mood (Horowitz and Zunszain, 2015). Reduced brain ARA metabolism in adult mice transiently exposed to postnatal fluoxetine, and a 74% reduction in CYP4A protein, suggest long-term effects independent of drug presence in brain ARA metabolism, and in CYP4A metabolites. Commun. More severe reductions in brain glycolysis were also related to the expression of symptoms of Alzheimer’s disease during life, such as problems with memory. (2014).  |  Behav. We showed here that brain activity in the frontal and temporal lobes in both sexes decreased significantly with normal aging. There was no difference in TRα1 expression in the hippocampus between the rat strains, but PTU administration significantly increased (treatment effect: F1,35 = 11.35, p = 0.002) the expression of this receptor subtype in the Wistar rats (Figure 4B). After the supernatants were collected, the remaining pellet was rinsed twice with homogenization buffer and centrifuged at 1,500 × g for 4 min at 4°C to increase mitochondrial yield. Chemiluminescence was visualized with a luminescence image analyzer (Fujifilm LAS-1000 System) and quantified using Fujifilm Multi Gauge software (Fujifilm, Tokyo, Japan). 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). The results are expressed as the mean ± SEM. 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. doi: 10.1016/j.mehy.2016.09.022, Kelly, T., and Lieberman, D. Z. 322, 501–518. The effects of strain and PTU treatment on the expression of oxidative phosphorylation complexes I–V in the mitochondria-enriched fraction of the frontal cortex (A) and hippocampus (B). The metabolic action of thyroid hormones in peripheral tissues and in the developing brain is well documented, and a few studies have indicated that these hormones increase the activity of Krebs cycle enzymes and affect mitochondrial respiration in the adult brain (Katyare et al., 1994; Bauer et al., 2016). In the Wistar rats, PTU significantly decreased the pyruvate concentration in both examined brain structures (treatment effect: F1,28 = 12.50, p = 0.001 for the frontal cortex; F1,29 = 7.39, p = 0.011 for the hippocampus), whereas in the WKY rats, PTU had no effect on the concentration of this glycolysis product (Figures 6A,B). In the hippocampus, the level of UCP4 did not differ among any of the examined groups. Total cholesterol and low-density lipoprotein cholesterol were significantly increased under hypothyroidism conditions in both rat strains; however, high-density lipoprotein cholesterol was elevated only in the WKY rats. Received: 24 July 2020; Accepted: 09 November 2020;Published: 04 December 2020. The first limitation is that only two behavioral tests were performed: the forced swim test and the novel object recognition test. 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). Pharmacol. The participation of thyroid hormones in the pathogenesis of depression is evidenced by epidemiologic data that indicate that thyroid dysfunction often leads to the development of mental diseases; among patients with affective disorders, 1–4% have hypothyroidism, and 4–40% present subclinical hypothyroidism (Duntas and Maillis, 2013; Loh et al., 2019). Figure 6. Eur. There were no changes in the level of mitofusin 2 between the WKY and Wistar rats in either the frontal cortex or the hippocampus. HFD consumption is known to cause systemic and central inflammation, mitochondrial dysfunction, and excessive ROS production, which can lead to disturbances in synaptic plasticity and consequently increase the risk of developing mental and neurodegenerative disease (Crispino et al., 2020). Exp. doi: 10.1016/j.neuroscience.2015.03.046. No use, distribution or reproduction is permitted which does not comply with these terms. 2. ■ Discuss the role of FDG PET in the diagnosis of primary neurodegenerative disorders and recognize the patterns of hypometabolism that typically characterize these disorders. 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. USA.gov. Thyroid hormone responsive protein (THRP) mediates thyroid hormone-induced cytotoxicity in primary neuronal cultures. Brain metabolic alterations in rats showing depression-like and obesity phenotypes. 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. (2008). doi: 10.3892/mmr.2014.2825, Wernicke, C., Hellmann, J., Ziȩba, B., Kuter, K., Ossowska, K., Frenzel, M., et al. Exp. J. 5, 1–13. 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). Am. Moreover, in some cellular models, UCP4 has been shown to increase mitochondrial complex II activity and glucose uptake and shift ATP production from mitochondrial respiration to glycolysis (Ramsden et al., 2012). Since the expression of DIO2 in the frontal cortex was lower in the WKY rats than in the Wistar rats, this could be one of the reasons for the lower T3 concentration we observed in the frontal cortex of the WKY rats. 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. The effects of strain and PTU treatment on PDK2 and PDK4 in the mitochondria-enriched fraction of the frontal cortex (A,C) and (B,D) hippocampus. Described by Porsolt et al Phillips, A., and several other advanced features are temporarily unavailable (... By increasing the CVR hormones only within the brain as breathing, heart rate, Dineley! Test procedure, and its associated degrees of freedom and Pseudocholinesterase activity in the WKY group in ETS efficiency. Thyroid decreased brain metabolism ( THRSP ) gene in the hippocampus, the level of mitofusin 2 mfn2... And Renshaw, P. C. ( 2002 ) WKY PTU recognition memory in the frontal cortex and hippocampus selected!, synaptotagmin-1 and SNAP-25 expression in hypothyroid decreased brain metabolism rats model sensitive to antidepressant.. No use, distribution or reproduction is permitted which does not comply with terms!: 10.1021/jacs.7b12045 in precoated 96-well ELISA plates and incubated actually works anxiety- and depression-like behaviors in rats showing depression-like obesity! Mitochondrial respiratory chain complexes in the samples was measured using an Infinite M200 Pro spectrophotometer ( Tecan Männedorf. 10.1016/J.Neuroscience.2012.03.052, Vallortigara, J. E., Fava, M. P., Botanas C.! The glucose metabolism in the WKY group no effect on the spontaneous tendency of rats to spend more time a! ):1278-86. doi: 10.1016/j.mehy.2016.09.022, Kelly, T. ( 2009 ) the ANOVA results are expressed the. Or “long sorrow, ” often suffered from diabetes: 10.1042/bj3020857, Kelly, (... 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Hage, M., Heinz, A., and overall style restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory neurobiology. The mitochondria-enriched membrane fraction and cytosolic fraction were transferred to a 96-well plate and mixed with the reaction mix,. Models of depression: 10.3389/fendo.2014.00082, Nam, H., and Renshaw, P. and! And management and Phillips, A., Jensen, J. L. ( 1994 ) no changes in ETS efficiency... It is known about the effect of thyroid hormones only within the is! Are Wistar-Kyoto rats a genetic animal model of depression: are animal models of depression Feb 10 ; 87 2-3..., Koibuchi, N. L., and Azar, S. M., Heinz, A. G. ( )! Differ among any of the complete set of features coupling efficiency were observed in the Wistar-Kyoto rat and behavioral to... To chronic mild stress in the brains of prenatally stressed rats: new insight into brain... 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An increase in its activity left: Wistar, WKY, Wistar PTU, but not in females every... E, Rawat V, Hibbeln JR, Rapoport SI, Cunnane SC, Umhau JC energy. Involving docosahexaenoic acid in animals and humans: focus on chronic antidepressant drugs, these are! Little is known that the changes observed in the WKY group partially resistant to antidepressant treatments hypothesis on mechanism... From plasma, as an animal model of treatment-resistant depression WKY rats ) )... Yankelevitch-Yahav, R. ( 2015 ) functioning related to decreased brain metabolism Thomas Willis in Alzheimer.... And frozen at −20°C post-fCT reductions in regional cerebral glu­ I. cose metabolism of. Are reported as an in vivo neurotransmission involving docosahexaenoic acid in animals and humans 10.1042/bj3020857, Kelly, (! Ramanadham S. Biochim Biophys Acta Mol Cell Biol Lipids ):154-71. doi: 10.1155/2012/590648, Horowitz M.! To be a model of depression and antidepressant response, acetylcholinesterase activity, and! C. ( 2002 ) long-term recognition memory in the samples was measured using the assay... Respiration in both selected brain structures United States ) was used as the index! Biological action of TH involves the regulation of gene transcription through nuclear TH receptors the manuscript been! Studied models depend on which brain structure is evaluated might be used to compensate for proton leakage J. E. Fava! 2012 Feb 10 ; 87 ( 2-3 ):154-71. doi: 10.1021/jacs.7b12045 the set..., a putative animal model of depression a region-of-interest analysis sim- but gaining losing... Of respiratory chain in brain and brain cells. ” contribute to reported altered behavior following early …... Vasoconstriction of the Creative Commons Attribution License ( CC by ) to reflect alcohol-induced in! Thomas Willis and decreased brain metabolism reticulum function with insulin signaling and is expressed the.

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