Chronic mild stress induces widespread decreases in thyroid hormone α1 receptor mRNA levels in brain—Reversal by imipramine

2009 ◽  
Vol 34 (2) ◽  
pp. 281-286 ◽  
Author(s):  
Edward J. Stein ◽  
Nylson G. da Silveira Filho ◽  
Danilo C. Machado ◽  
Débora C. Hipólide ◽  
Karen Barlow ◽  
...  
1994 ◽  
Vol 143 (1) ◽  
pp. 107-120 ◽  
Author(s):  
H Wallace ◽  
K McLaren ◽  
R Al-Shawi ◽  
J O Bishop

Abstract The herpes simplex type 1 virus thymidine kinase (HSV1-TK) reporter gene was coupled to a bovine thyroglobulin promoter (TG-tk construct). Within the thyroid glands of transgenic mice expression was confined to thyroid follicle cells. Infusion of Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) to 8 to 12 week transgenic females led to the complete loss of thyroid HSV1-TK activity (at 3 to 4 days) and thyroid follicles (between 7 and 14 days). During the first 5 days of treatment a single reciprocal oscillation in circulating thyroxine (T4) and TSH levels occurred. By 14 days the circulating triiodothyronine (T3) and T4 levels of all treated animals were below the detection limits of the assays, while TSH levels were elevated ten-fold and continued to increase thereafter. During 14 days of treatment the thyroids regressed, protein content fell by 80–90% and the C cells, normally dispersed within the central region of each gland, came together in aggregates. Pituitary GH levels in females rose and fell back to normal within 14 days and between 14 and 28 days fell to a level comparable with that of GH-deficient lit/lit mice. The levels of hepatic GH receptor mRNA and the predominant 6·6 kb T3 receptor mRNA were unaffected by thyrocyte ablation. Thyrocyte ablation had no effect on the level of prolactin (Prl) receptor mRNA in females, but increased Prl receptor mRNA levels in males and eliminated group 1 major urinary protein (MUP) mRNA in females. T4 replacement reversed the effects of thyrocyte ablation on MUP mRNA in females and on Prl receptor mRNA in males. Despite the many physiological changes induced by thyrocyte ablation, ablated mice have been maintained for up to 1 year without thyroid hormone supplementation. T4-deficient females were normally fertile and carried pups to term. Although transgenic males expressed HSV1-TK ectopically in spermatids and spermatozoa at levels similar to thyrocyte levels, a rate of Ganciclovir infusion which successfully ablated the thyrocytes did not affect the testis. As an alternative to infusion by minipump, thyrocyte ablation could be achieved by 6 twice-daily injections of Ganciclovir, at a level of 112 μg Ganciclovir/g body weight per day, and fetuses in utero could be thyrocyte ablated by administering 50 or 15 μg/g body weight per day to pregnant females between days 14 and 18 of gestation. These data demonstrate the potential value of transgenic thyrocyte ablation in the study of the effects of thyroid hormone deprivation. Journal of Endocrinology (1994) 143, 107–120


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Raffaella Molteni ◽  
Andrea C. Rossetti ◽  
Elisa Savino ◽  
Giorgio Racagni ◽  
Francesca Calabrese

Although activity-dependent transcription represents a crucial mechanism for long-lasting experience-dependent changes in the hippocampus, limited data exist on its contribution to pathological conditions. We aim to investigate the influence of chronic stress on the activity-dependent transcription of brain-derived neurotrophic factor (BDNF). Theex vivomethodology of acute stimulation of hippocampal slices obtained from rats exposed to chronic mild stress (CMS) was used to evaluate whether the adverse experience may alter activity-dependent BDNF gene expression. CMS reduces BDNF expression and that acute depolarization significantly upregulates total BDNF mRNA levels only in control animals, showing that CMS exposure may alter BDNF transcription under basal conditions and during neuronal activation. Moreover, while the basal effect of CMS on total BDNF reflects parallel modulations of all the transcripts examined, isoform-specific changes were found after depolarization. This different effect was also observed in the activation of intracellular signaling pathways related to the neurotrophin. In conclusion, our study discloses a functional alteration of BDNF transcription as a consequence of stress. Being the activity-regulated transcription a critical process in synaptic and neuronal plasticity, the different regulation of individual BDNF promoters may contribute to long-lasting changes, which are fundamental for the vulnerability of the hippocampus to stress-related diseases.


2021 ◽  
Vol 55 (3) ◽  
pp. 153-162
Author(s):  
Jana Osacka ◽  
Romana Koprdova ◽  
Andrej Tillinger ◽  
Zdenko Pirnik ◽  
Alexander Kiss

Abstract Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures. Methods. The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured. Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels. Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.


2000 ◽  
Vol 25 (3) ◽  
pp. 247-257 ◽  
Author(s):  
Nassia Kioukia ◽  
Stathis Bekris ◽  
Katerina Antoniou ◽  
Zeta Papadopoulou-Daifoti ◽  
Ion Christofidis

2016 ◽  
Vol 33 (S1) ◽  
pp. S525-S525
Author(s):  
A. Sayd ◽  
K. MacDowell ◽  
L. Monteagudo ◽  
D. Martin ◽  
J.L. Madrigal ◽  
...  

Perivascular macrophages (PVM) are hematopoyetic cells that migrate to the brain perivascular space modulating the interactions between the immune and central nervous systems (CNS). Previously, their depletion with the icv administration of the pro-apoptotic drug clodronate encapsulated in liposomes increased the vascular production of the proinflammatory prostaglandin E2 (PGE2), the release of ACTH, corticosterone and fever, induced by the intravenous administration of Lipopolysaccharide (LPS). Further studies also demonstrated a decrease in the synthesis of the anti-inflammatory prostaglandin 15d-PGJ2.With this background, we decide to deeper explore the mechanisms involved in the anti-inflammatory profile of PVM by depleting them in a model of depression induced by chronic mild stress (CMS) exposure in rats.Our results showed an increase of the proinflammatory cytokines TNFα, IL-1 and IL-6 at mRNA levels in the prefrontal cortex of the groups of animals where the PVM were depleted, as well as in the protein levels of the pro-inflammatory nuclear factor NF-κB, the enzymatic pro-inflammatory enzymatic sources iNOS, COX-2 and m-PGES-1 and their product PGE2. A concomitant decrease of the 15d-PGJ2 mediator was also observed. In addition, we also checked whether the depletion of PVMs could regulate the expression of molecules implicated in the leukocyte traffic and infiltration in the CNS in our CMS model. Thus, the mRNA levels of the chemokines MCP-1, fractalkine and the adhesion molecule VCAM appeared increased in the animals without PVMs.In summary, our results could suggest a potential anti-inflammatory role for PVMs in a depression model chronic stress-induced as CMS.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2016 ◽  
Vol 113 (32) ◽  
pp. E4726-E4735 ◽  
Author(s):  
Peng Wang ◽  
Hui Li ◽  
Swapnali Barde ◽  
Ming-Dong Zhang ◽  
Jing Sun ◽  
...  

The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG). Only Galr1 mRNA levels were significantly increased, and only in the latter region. After knocking down Galr1 in the vPAG with an siRNA technique, all parameters of the depressive behavioral phenotype were similar to controls. Thus, the depression-like behavior in rats exposed to CMS is likely related to an elevated expression of Galr1 in the vPAG, suggesting that a GALR1 antagonist could have antidepressant effects.


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