Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rodent models provide a valuable approach to elucidating the pathophysiological mechanisms underlying the deleterious effects of childhood trauma and stress. Neonatal rats and mice emit ultrasonic vocalizations (USVs) when separated from the dam and litter. USVs are suppressed in rat pups by exposure to the putatively infanticidal threat of an adult male. In the present study, C57BL/6J mouse pups were exposed to an anaesthetized (non-sire) adult C57BL/6J male for 3-min/day from postnatal days 2-14, and subsequently tested for anxiety-related behaviors (using the novel open field, elevated plus-maze, light/dark exploration tests) and depression-related behavior (using the forced swim test) at 11 weeks of age. In a separate cohort, hypothalamic-pituitary-adrenal-axis activation was measured via plasma corticosterone levels following either a single male-exposure or separation episode. Results showed that pups exposed to an adult male emitted significantly fewer USVs than separation-only counterparts. Corticosterone levels were significantly lower following single exposure to the adult male than separation alone. Repeated neonatal male-exposure did not lead to significant alterations in anxiety- or depression-related behaviors in adulthood. Taken together, present data suggest that the form of adult male-exposure employed did not act as a significant stressor, at least in this mouse strain. Further studies will be needed to determine whether alternative mouse strains, exposure protocols or adult behavioral assays will produce a different pattern of short-term and long-term effects.
 ...
PMID:Short-term and long-term effects of postnatal exposure to an adult male in C57BL/6J mice. 1748 87

Although traditionally considered to be etiological factors in depression, corticosteroids have been shown to exert an acute antidepressant action under some conditions. To investigate the mechanism of this effect, the present experiment sought to develop an animal model of it in mice using the repeated forced swim procedure. Corticosterone or desmethylimipramine was administered in the drinking water before, during or after repeated daily forced swims or a tail suspension test. Glucocorticoid and mineralocorticoid receptor involvement were assessed by coadministration of RU486 or spironolactone. Plasma corticosterone and fos expression in the paraventricular nucleus of the hypothalamus and piriform cortex were also measured in the treated animals. Corticosterone, given either before/during or after repeated swim, was found to produce a rapid reduction of immobility that was greater than that produced by desmethylimipramine given by the same route and dose and for the same duration. There was a nonsignificant tendency toward this effect in the tail suspension test. RU486 failed to block the effect but results with spironolactone were ambiguous. Plasma corticosterone was elevated in an inverted U-shaped fashion by the hormone treatment. Fos expression in response to the last swim was blunted in the paraventricular hypothalamus but enhanced in the piriform cortex. It is concluded that short-term treatment with corticosterone has a marked antidepressant effect in the mouse repeated forced swim test and merits further consideration as a short-term therapeutic agent in low doses. The hormone may act by suppression of neural activity in central stress circuits leading to a disinhibition of regions involved in active behavioral coping.
 ...
PMID:An anti-immobility effect of exogenous corticosterone in mice. 1802 53

Inflammation is implicated in several medical conditions that are sexually dimorphic, including depression, cardiovascular diseases, autoimmunity, and presumably cancer progression. Here we studied the effects of the proinflammatory agent, LPS, on MADB106 lung tumor retention (LTR), and sought to elucidate underlying mechanisms and sexual dimorphism. F344 male and female rats were administered with LPS (0.001-1mg/kg i.v.) simultaneously with tumor cell inoculation, and treated with a beta-blocker (nadolol, 0.2-0.3mg/kg s.c.), a COX inhibitor (indomethacin, 4mg/kg s.c.) or both drugs. To study the role of NK cells, numbers and cytotoxicity of marginating-pulmonary NK cells were studied, and selective in vivo NK-depletion was employed. Serum levels of corticosterone, IL-6, and TNF-alpha were also assessed. The findings indicated that LPS increased LTR in both sexes, but 10-fold higher doses were needed in females to reach the increase evident in males. Additionally, nadolol and indomethacin reduced the effects of LPS, more so in males. In vivo NK-depletion and ex vivo NK activity studies suggested that LPS affected LTR through both NK-independent and NK-dependent mechanisms, the latter mediated through prostaglandin release in males. Corticosterone, IL-6, and TNF-alpha responses to LPS were sexually dimorphic, but were not associated with LPS or drugs' impacts on LTR. Overall, our findings demonstrate sexual dimorphism in LPS-induced elevated susceptibility to MADB106 experimental metastasis, and in potential humoral underlying mechanisms. Further studies are needed to elucidate additional immunological and non-immunological mediators of these dimorphisms, as well as to assess their involvement in other sexually dimorphic pathologies that are associated with inflammation.
 ...
PMID:Metastatic-promoting effects of LPS: sexual dimorphism and mediation by catecholamines and prostaglandins. 1895 72

Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb+PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 microg/kg (females) or 100 or 150 microg/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb+PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb+PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments.
 ...
PMID:Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: a potential biological unifying mechanism for their corresponding disease profiles. 1897 74

Corticosterone, a principal glucocorticoid synthesized in the rodent adrenal cortex and secreted in response to stress, is reported to produce a biphasic effect on animal behavior. In this study, we determine that corticosterone administration produced different effects on depression-like behavior in mice depending on the length of time it was administered. In addition, we explored the indirect evidence at the cellular and molecular levels in order to support above assertion. Male mice received repeated injections of the vehicle and 20 mg/kg of corticosterone for 6, 18, and 36 days before being subjected to the forced swimming and tail suspension tests. After behavioral tests, we analyzed the number of neuron-specific nuclear protein (NeuN)-positive cells in the hippocampus, and the levels of two important cytoskeleton proteins, microtubule-associated protein 2 (MAP2) and neurofilament light chain protein (NF-L). Our results showed that 18-day and 36-day corticosterone injections caused increased depression-like behavior in male mice and significantly reduced the NF-L protein levels in the hippocampal tissues. However, 6-day corticosterone injection exhibited an anti-depressant effect accompanied by increased levels of MAP2 and NF-L in the hippocampus. Interestingly, no decrement was observed in NeuN-positive cells in the entire hippocampus throughout the experiments. The results support the view that short-term and long-term corticosterone administration produce opposite effects on depression-like behavior. Furthermore, the biphasic regulation of cytoskeleton proteins in the hippocampus might be a mechanism by which corticosterone treatments influence animal behavior.
 ...
PMID:The varying effects of short-term and long-term corticosterone injections on depression-like behavior in mice. 1940 Nov 66

Elevated levels of corticosteroids and stress play key roles in the pathophysiology of affective disorders. Corticosterone (CORT)-treated rats have emerged as a pharmacological model of depression-like behaviors. Previous studies have shown that CORT administration induces neuronal atrophy in the CA3 subfield of the hippocampus and laminae II/III of the prefrontal cortex. However, little attention has been given to other limbic structures such as the amygdala and the nucleus accumbens (NAcc). We investigated here whether 3 weeks of CORT administration in rats causes dendritic remodeling and spine density reorganization in the basolateral amygdala and pyramidal neurons of the CA1 subfield of the hippocampus as well as in spiny medium neurons of NAcc. Quantitative morphological analysis revealed retracted neuronal arborizations and modified configuration of length depending on branch order in medium spiny neurons of the NAcc of CORT-treated animals. Moreover, distal dendritic sections of the NAcc showed massive reductions in the number of spines caused by the CORT treatment. This treatment also induced a reduction in total dendritic length specific to fourth and sixth branch orders of pyramidal CA1 hippocampal neurons. These neurons also showed decreased branching and diminished number of spines. Finally, pyramidal neurons of the basolateral amygdala were apparently not significantly affected by the CORT treatment. Taken together, these data show for the first time neuronal morphological alterations in the NAcc in the CORT model of depression-like behaviors. Our results also add further information about the morphological reorganization occurring in CORT-sensitive regions of the limbic system.
 ...
PMID:Morphological reorganization after repeated corticosterone administration in the hippocampus, nucleus accumbens and amygdala in the rat. 1950 71

The detailed mechanisms of emotional modulation in the nervous system by opioids remain to be elucidated, although the opioid system is well known to play important roles in the mechanisms of analgesia and drug dependence. In the present study, we conducted behavioral tests of anxiety and depression and measured corticosterone concentrations in both male and female mu-opioid receptor knockout (MOP-KO) mice to reveal the involvement of mu-opioid receptors in stress-induced emotional responses. MOP-KO mice entered more and spent more time in the open arms of the elevated plus maze compared with wild-type mice. MOP-KO mice also displayed significantly decreased immobility in a 15 min tail-suspension test compared with wild-type mice. Similarly, MOP-KO mice exhibited significantly decreased immobility on days 2, 3, and 4 in a 6 min forced swim test conducted for 5 consecutive days. The increase in plasma corticosterone concentration induced by tail-suspension, repeated forced swim, or restraint stress was reduced in MOP-KO mice compared with wild-type mice. Corticosterone levels were not different between wild-type and MOP-KO mice before stress exposure. In contrast, although female mice tended to exhibit fewer anxiety-like responses in the tail-suspension test in both genotypes, no significant gender differences were observed in stress-induced emotional responses. These results suggest that MOPs play an important facilitatory role in emotional responses to stress, including anxiety- and depression-like behavior and corticosterone levels.
 ...
PMID:Reduced emotional and corticosterone responses to stress in mu-opioid receptor knockout mice. 1959 19

Our objective in the present study was to examine 5-HT(1A) receptor function in prefrontal cortex and hippocampus of GR+/- mice, which appear to be an appropriate murine model of depression. 5-HT(1A) receptor function was determined by measuring [(35)S]GTPgammaS binding stimulated by the 5-HT(1A) receptor agonist 8-OH-DPAT (1 microM), an indication of the capacity of the receptor to activate G proteins. 5-HT(1A) receptor expression was determined by measuring the binding of [(3)H]8-OH-DPAT (2 nM). We observed no effect of the constitutive reduction in GR on 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding or 5-HT(1A) receptor binding sites. Corticosterone treatment (10mg/kg, sc once daily for 21 days) of wild-type mice resulted in a decrease in 5-HT(1A) receptor function in prefrontal cortex [8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (% above basal), vehicle-treated: 39+/-4.9; corticosterone-treated: 17+/-2.8], but not in hippocampus. The constitutive reduction in GR expression prevented the down-regulation of 5-HT(1A) receptor function in frontal cortex by chronic corticosterone administration. In contrast, corticosterone treatment of GR+/- mice resulted in an increase in 5-HT(1A) receptor function in hippocampus which reached statistical significance in CA2/3 region [8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (% above basal), vehicle-treated: 41+/-9.7; corticosterone-treated: 94+/-23]. These changes seem to be evoked by a combined effect of high corticosterone levels and GR deficiency. Although GR+/- mice do not exhibit changes in baseline corticosterone, the constitutive deficiency in GR appears to have unmasked regulatory effects of elevated corticosterone in the maintenance of 5-HT(1A) receptor function in prefrontal cortex and hippocampus.
 ...
PMID:Regulation of cortical and hippocampal 5-HT(1A) receptor function by corticosterone in GR+/- mice. 1976 2

Antidepressants have been shown to be neuroprotective and able to reverse damage to glia and neurons. Thyrotropin-releasing hormone (TRH) is an endogenous antidepressant-like neuropeptide that reduces the expression of glycogen synthase kinase-3beta (GSK-3beta), an enzyme that hyperphosphorylates tau and is implicated in bipolar disorder, diabetes and Alzheimer's disease. In order to understand the potential role of GSK-3beta in the modulation of depression by TRH and TRH-like peptides and the therapeutic potential of GSK-3beta inhibitors for neuropsychiatric and metabolic diseases, young adult male Sprague-Dawley (SD) rats were (a) injected ip with 1.8mg/kg of GSK-3beta inhibitor VIII (GSKI) and sacrificed 0, 2, 4, 6, and 8h later or (b) injected with 0, 0.018, 0.18 or 1.8mg/kg GSKI and bled 4h later. Levels of TRH and TRH-like peptides were measured in various brain regions involved in mood regulation, pancreas and reproductive tissues. Large, 3-15-fold, increases of TRH and TRH-like peptide levels in cerebellum, for example, as well as other brain regions were noted at 2 and 4h. In contrast, a nearly complete loss of TRH and TRH-like peptides from testis within 2h and pancreas by 4h following GSKI injection was observed. We have previously reported similar acute effects of corticosterone in brain and peripheral tissues. Incubation of a decapsulated rat testis with either GSKI or corticosterone accelerated release of TRH, and TRH-like peptides. Glucocorticoids, via inhibition of GSK3-beta activity, may thus be involved in the inhibition of TRH and TRH-like peptide release in brain, thereby contributing to the depressogenic effect of this class of steroids. Corticosterone-induced acceleration of release of these peptides from testis may contribute to the decline in reproductive function and redirection of energy needed during life-threatening emergencies. These contrasting effects of glucocorticoid on peptide release appear to be mediated by GSK-3beta.
 ...
PMID:Rapid modulation of TRH and TRH-like peptide release in rat brain, pancreas, and testis by a GSK-3beta inhibitor. 2033 9

We examined a potential two-hit murine animal model of depression by assessing whether a genetic deficit in reelin increases vulnerability to the depressogenic effects of the stress hormone corticosterone. Stress is an identified risk factor for the onset of depressive symptoms, but depression also has a significant genetic component, suggesting that environmental factors and genetic background likely interact in the etiology of depression. Previous results have revealed that reelin levels are decreased in post-mortem hippocampal tissue from patients with schizophrenia, bipolar disorder and depression, and also in an animal model of depression. Therefore, we hypothesized that heterozygous reeler mice (HRM), with approximately 50% normal levels of reelin, would be more sensitive to the depressogenic effects of corticosterone than wild-type mice (WTM). Mice received subcutaneous injections of either vehicle or 5 mg/kg, 10 mg/kg, or 20 mg/kg of corticosterone for 21 consecutive days, and then they were assessed for changes in depression-like behavior, hippocampal reelin expression, and hippocampal neurogenesis. Corticosterone produced dose-dependent increases in depression-like behavior and decreases in reelin expression, neurogenesis, and cell maturation regardless of mouse genotype. There were no differences between the vehicle-injected HRM and WTM in these measures. However, the effects of CORT on behavior, the number of reelin-positive cells in the subgranular zone or hilus, and hippocampal neurogenesis were more pronounced in the HRM than in the WTM, providing support for the idea that mice with impaired reelin signaling may be more vulnerable to the deleterious effects of glucocorticoids. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
 ...
PMID:Reelin as a putative vulnerability factor for depression: examining the depressogenic effects of repeated corticosterone in heterozygous reeler mice. 2084 64


<< Previous 1 2 3 4 5 6 7 8 Next >>