Antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism

Conceição, Rodrigo Rodrigues da; Laureano‐Melo, Roberto; Oliveira, Kelen Carneiro; Melo, Maria Clara de Carvalho; Kasamatsu, Tereza Sayoko; Maciel, Rui M. B.; Souza, Janaína Sena de; Giannocco, Gisele

doi:10.1016/j.physbeh.2016.02.005

Cited by 9 publications

(6 citation statements)

References 48 publications

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“…Additionally, Ge et al (27) reported reduction in swimming time in both clinical and subclinical hypothyroid rats. In contrast, Yu et al (30) and da Conceicao et al (31) reported decreased immobility time in adult rats with hypothyroidism. As there is a paucity of research evaluating depression-like behavior in juvenile rats with hypothyroidism, we were not able to compare our findings with other studies.…”

Section: Discussionmentioning

confidence: 88%

“…There are many animal studies suggesting that thyroid hormones influence norepinephrine and serotonin levels which play crucial role in depression pathogenesis (31,37,38,39,40). A recent study, which aimed to explore the underlying mechanism of a link between thyroid and serotoninergic system, suggested that the lateral habenula might play a role in depression-like behavior in rats with hypothyroidism (29).…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats

Erdoğan

Özgür²,

Aksu³

et al. 2016

Jcrpe

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Objective:The aim of this study was to investigate depression-like behaviors of juvenile rats with congenital and postnatal hypothyroidism.Methods:Twenty-seven newborn rat pups were used. First, 6-month-old Wistar Albino female rats were impregnated. Methimazole (0.025% wt/vol) was given to dam rats from the first day of pregnancy until postnatal 21 days (P21) to generate pups with congenital hypothyroidism (n=8), whereas in the postnatal hypothyroidism group (n=10), methimazole was given from P0 to P21. In the control group (n=9), dam rats were fed ad libitum and normal tap water. Offspring were fed with breast milk from their mothers. The behavioral parameters were measured with the juvenile forced swimming test (JFST). The procedure of JFST consisted of two sessions in two consecutive days: the 15-minute pre-test on day 1 and the 5-minute test on day 2.Results:Increased immobility and decreased climbing duration were observed in both congenital and postnatal hypothyroidism groups. Decreased swimming duration was detected in the postnatal hypothyroidism group. Both hypothyroidism groups had a lower body weight gain compared with the control group, while the congenital hypothyroidism group had the lowest body weight.Conclusion:Our results showed that hypothyroidism had negative effects on depression-like behavior as well as on growth and development. Both congenital and postnatal hypothyroidism caused an increase in immobility time in JFST. New studies are required to understand the differing results on depression-like behavior between congenital and postnatal hypothyroidism.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats

Erdoğan

Özgür²,

Aksu³

et al. 2016

Jcrpe

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“…T3 is especially required for the generation and maturation of neurons and axonal myelination partly owing to its higher affinity for thyroid receptors (TRs) than T4 which is more abundant [38, 39]. Several studies documented neurotropic actions of T3 that can be potentially neuroprotective under stroke, including reduction of developmental neuronal apoptosis, decreased glutamate transfer into brain cell and increased brain-derived neurotrophic factor (BDNF) [40–43]. In the one side, microarray technology and bioinformatic analysis have been widely used to screen genetic alterations at the genome level.…”

Section: Discussionmentioning

confidence: 99%

Low free triiodothyronineis predicts worsen neurological outcome of patients with acute ischemic stroke: a retrospective study with bioinformatics analysis

Zhang

Zhao

et al. 2019

BMC Neurol

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BackgroudPatients with acute ischemic stroke (AIS) often experience low serum free triiodothyronine (FT3), but the association of low FT3 with stroke severity, subtype and prognosis has not yet been thoroughly studied, and the molecular events underlying these clinical observation were also unclear.MethodsWe retrospectively collected 221 cases of AIS and 182 non-AIS cases with detailed clinical data from our department. FT3 concentrations were measured on admission to predict functional outcome within 3 months using multivariable models adjusted for other risk factors. Receiver operating characteristic (ROC) curves were calculated to define the best cutoff value of FT3 of stroke severity, subtypes and neurological outcome. Gene set enrichment, pathway mapping and network analyses of deferentially expressed genes (DEGs) were performed.ResultsFT3 was significantly decreased in AIS patients with National Institutes of Health Stroke Scale (NIHSS) > 3 and 3-months modified Rankin Scale (mRS) > 2. The cut-off value of FT3 for NIHSS on admission was 4.30 pmol/L. Also, FT3 level was significantly lower in large artery atherosclerosis (LAA) group and cardioembolism (CE) group than that in small vessel occlusion (SVO). FT3 value served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38 pmol/l. Gene ontology (GO) analysis showed that the biological function of DEGs was mainly enriched in multicellur organism, neuron differentiation and cellular response to hypoxia. The cellular components were involved in extracelluar region, exosome and matrix, and the molecular functions were transcriptional activator activity, DNA binding and nuclear hormone receptor binding. Signal pathways analysis was indicative of neuroactive ligand-receptor interaction, thyroid hormone signaling pathway, and protein digestion and absorption these DEGs were involved in. Six related gene were identified as hubs from the protein-protein interaction (PPI) networks. Three modules were selected from PPI, of which MMP4, ADRA2C and EIF3E were recognized as the seed genes.ConclusionsLow FT3 value on admission was associated with stroke severity, subtype and prognosis. In addition, DEGs identified from bioinformatics analysis are likely to be candidates for elucidating clinical outcomes with low FT3, and provide us with therapeutic targets for improving stroke prognosis.

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“…Studies have shown that the use of levothyroxine as a complement in the treatment of mood disorders helps to improve the results [122] . Interestingly, a study conducted by our group, showed that animals that have undergone thyroidectomy presented antidepressant behavior due to hippocampal hypothyroidism, since genetic expression of MCT8 and DIO2 was significantly decreased, while animal behavior assessments showed no depressant behavior, corroborated by swimming test results [47] .…”

Section: Th Receptorsmentioning

confidence: 73%

“…Together, it is believed that some patients suffer from central hypothyroidism, a condition that is associated with inappropriate TH transport, inappropriate deiodination and inappropriate response of the receptors [45,46] . A lack of TH can induce not only peripheral deficiency of the hormone, but also clear cases of hippocampal hypothyroidism, characterized by a significant decrease in the expression of important genes associated with thyroid metabolism, such as MCT8 and THR α1 [47] . As already reported, the thyroid hormone influences mood and behavior through several molecular bases whose origins are not fully understood [48] .…”

Section: Thyroid Hormone and The Central Nervous Systemmentioning

confidence: 99%

The Hypothyroid Brain

Souza

Conceição

Oliveira

et al. 2016

Receptors Clin Investig

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The thyroid gland is controlled by a feedback system, the hypothalamus-pituitary-thyroid axis, and produces thyroid hormone (TH), which plays a critical role in growth, development and cellular metabolism. Diseases of the thyroid are well defined clinically and biochemically and diseases affecting thyroid function can cause both clinical hypothyroidisms, the most common cause of thyroid dysfunction, occurs when there is a decrease in the production of thyroid hormones, and hyperthyroidism, when there is an increase in hormone production. Common systemic manifestations of hypothyroidism include fatigue, dry skin, weight gain, hair loss, cold intolerance, hoarseness and constipation. Patients affected by this condition present a number of central and peripheral signs in the nervous system that may be neurological manifestations that occur along with the systemic disease. The conversion of thyroid hormone in the target tissue is done by three distinct deiodinases: type I, type II and type III. Each deiodinase has a different function in order to maintain thyroid hormone homeostasis in the tissues. Other proteins important for thyroid state are the TH transporters. MCT8, OATP1C1 and LAT1 and 2 transporters regulate T4 and T3 flow in the cells. The action of THs depends on the interaction of several proteins that are specialized in the control of thyroid hormone homeostasis not only in the brain but also in various tissues. THs are important for the maturation of the brain from the intrauterine period and remain important to adulthood. When there is some disturbance in the control mechanisms for the state of thyroid hormone, the consequences to the tissues, especially the CNS, can range from mild damage to severe impairment in neuronal development.

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Antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism

Cited by 9 publications

References 48 publications

The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats

The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats

Low free triiodothyronineis predicts worsen neurological outcome of patients with acute ischemic stroke: a retrospective study with bioinformatics analysis

The Hypothyroid Brain

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