Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolation of adult animals represents a form of psychological stress from which the animals cannot escape. In order to assess the effect of this stressor on neurochemical substrates in the brain, we assessed behavior and measured tyrosine hydroxylase and proenkephalin mRNA levels in selected brain areas by in situ hybridization histochemistry. Tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (LC) were significantly and progressively increased by 18, 42 and 68% after 7, 14 or 28 days of isolation, respectively. TH mRNA in the midbrain was transiently increased by isolation. Levels were significantly elevated by 34 and 48% above group-housed controls in the ventral tegmentum and the substantia nigra, respectively, after 14 days of isolation. In the forebrain, proenkephalin (PE) mRNA levels were found to be transiently decreased by 29% in the anterior and medial aspects of the caudate-putamen and the nucleus accumbens after 7 or 14 days of isolation stress, but the levels returned toward control levels after 28 days of isolation. Behavioral tests indicate that isolated animals progressively became more aggressive with duration of stress and showed a small but significant decrease in locomotor activity. The results demonstrate that a physically noninvasive stressor such as isolation of adult male rats can produce significant alterations in brain neurochemistry. The neurochemical responses observed may represent a brain mechanism designed to help the organism adapt to or protect from the deleterious effects of chronic psychological stress.
Brain Res Mol Brain Res 1991 Oct
PMID:Isolation stress increases tyrosine hydroxylase mRNA in the locus coeruleus and midbrain and decreases proenkephalin mRNA in the striatum and nucleus accumbens. 168 31

In recent years there has been considerable discussion of possible cross-regulatory mechanisms involving the immune system and the neuroendocrine system. Certainly, evidence of hormonal communication between these two systems would provide at least a partial explanation for the many anecdotal observations of physical and mental stress affecting disease course. In previous studies of a neoplastic lymphokine-responsive B cell clone, BCL1-3B3, we noted that these cells produced a lymphokine which could affect normal B cell growth and viability. Physical characterization of this lymphokine indicated that its molecular weight was identical to that of the neuroendocrine hormone adrenocorticotropin (ACTH). Since Blalock and colleagues had reported the production of ACTH by virally-infected B cells, we have investigated whether ACTH can functionally mimic the BCL1-3B3-derived lymphokine. The neuroendocrine hormone adrenocorticotropin (ACTH) can increase in vitro murine B lymphocyte proliferation when added at physiologically relevant concentrations between 10(-9) to 10(-11) M. ACTH does not mimic the action of any lymphokine known to be required for B cell proliferation such as IL-2, IL-4, or IL-5. ACTH requires the presence of one or more of these known B cell stimulatory factors for its action and the most marked increase in B cell proliferation were noted in assays for IL-5 activity where 10(-10) M ACTH increased thymidine incorporation up to five-fold. Using two-stage assays, we determined that ACTH acts during the latter stages of B cell activation (i.e., 3-4 days after initial stimulation with either the combination of IL-4, GAMIg-Sepharose, and IL-1 or the combination of DxS and IL-5). These data indicate a direct role for a stress-induced neuroendocrine hormone in modulating the course of a humoral immune response.
J Mol Cell Immunol 1990
PMID:Adrenocorticotropin (ACTH) functions as a late-acting B cell growth factor and synergizes with interleukin 5. 196 84

Changes in neuropeptide gene expression in the hypothalami of sheep subjected to psychological stress (isolation, 1 h; n = 3) or dehydration (48 h; n = 3) were examined using in-situ hybridization histochemistry. Compared with non-stressed euhydrated control animals (n = 3), isolation induced significant accumulation of mRNA for corticotrophin-releasing hormone, pro-enkephalin and pro-dynorphin (DYN) in the paraventricular nucleus (PVN), but no change in mRNA content within the supraoptic nucleus (SON). By contrast, dehydration significantly increased DYN mRNA in the magnocellular neurones of the PVN and SON. However, neither isolation nor dehydration altered the expression of mRNA for vasopressin (AVP) in either the PVN or the SON. These results indicate that in the ovine hypothalamus (1) stress represents a powerful stimulus to co-ordinated neuropeptide synthesis and (2) expression of DYN mRNA and AVP mRNA may be independently regulated during changes in plasma osmolality.
J Mol Endocrinol 1993 Oct
PMID:Isolation- and dehydration-induced changes in neuropeptide gene expression in the sheep hypothalamus. 829 74

Effects of conditioned emotional stimuli (CES), which induce psychological stress, on the expression of cerebral diazepam binding inhibitor (DBI) mRNA in mouse were examined using a communication box. Cerebral DBI mRNA expression significantly increased in a time-dependent manner after the application of CES. The maximal enhancement of DBI mRNA expression was observed 2 days after the application of CES, and this increase faded out over 7 days after the treatment. Flunitrazepam (1 mg/kg), an agonist for central benzodiazepine (BZD) receptors, completely abolished the CES-induced elevation of cerebral DBI contents and its mRNA expressions. These results indicate that cerebral DBI is enhanced by psychological stress, which is regulated by central BZD receptors.
Brain Res Mol Brain Res 2002 Jul 15
PMID:Psychological stress, but not physical stress, causes increase in diazepam binding inhibitor (DBI) mRNA expression in mouse brains. 1211 56

The glucocorticoid component of the stress response has been the subject of intense scientific scrutiny because of the wide ranging pathological consequences resulting from excess glucocorticoid exposure, including mood and anxiety disorders, and cognitive impairment. Exposure to stress activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic adrenomedullary system, which are regulated by neuronal pathways, including the inhibitory GABAergic (gamma-aminobutyric acid) system. Approximately 60% of the variance in glucocorticod levels may be attributable to genetic individual differences. In the present study, 56 healthy subjects underwent genotyping to determine the influence of the T1521C single nucleotide polymorphism (SNP) in the GABA(A)alpha6 receptor subunit gene (GABRA6) on the hormonal and autonomic responses to psychological stress induced by the Trier Social Stress Test (TSST). Adrenocorticotropin (ACTH), cortisol, diastolic blood pressure, and mean blood pressure responses to the TSST were significantly greater in subjects homozygous for the T allele or heterozygous compared to subjects homozygous for the C allele. Behavioral data was collected employing the Revised NEO Personality Inventory (NEO PI-R); subjects homozygous for the C allele scored significantly lower on the Extraversion factor compared to subjects homozygous for the T allele or heterozygous. These results suggest that the T1521C polymorphism in the GABRA6 gene is associated with specific personality characteristics as well as a marked attenuation in hormonal and blood pressure responses to psychological stress.
Mol Psychiatry 2004 Nov
PMID:GABRA6 gene polymorphism and an attenuated stress response. 1519 99

The mammalian acetylcholinesterase (ACHE) gene gives rise to diverse enzymatically active proteins with three different carboxyl termini. In the brain, the normally rare readthrough AChE-R monomer accumulates under embryonic development and in adults following psychological stress, head injury, or exposure to AChEs. In the prenatal developing cortex, its unique C-terminal peptide ARP associates with radial glial fibers supporting neuronal migration. In contrast, the major synaptic AChE-S variant appears in the migrating neurons themselves. Moreover, antisense suppression of AChE-R attenuates neuronal migration, allowing increased proliferation of neuronal progenitors. In the adult brain, neuronal AChE-R is either secreted or accumulates intraneuronally, where it interacts through ARP with the scaffold protein RACK1 and activated PKC-betaII. This associates with increased PKC-betaII activity, which shuttles to submembranal clusters (e.g., in hyperactivated hippocampal neurons). Cleavage yields the AChE-R-specific C-terminal peptide, including immunopositive ARP. Importantly, intrahippocampal injection of synthetic ARP was followed by its efficient neuronal penetration and retrograde transport into cortical and basal nuclei neurons. Moreover, ARP-injected mice presented increased stress-induced contextual fear, inhibitable by antisense suppression of AChE-R mRNA. Together, our findings point at the cleavable ARP peptide as a key regulator of neuronal development and plasticity and suggest its use as a drug target and/or research and therapeutic tool.
J Mol Neurosci 2006
PMID:ARP, the cleavable C-terminal peptide of "readthrough" acetylcholinesterase, promotes neuronal development and plasticity. 1669 Oct 12

The effects of stress, including their putative contribution to pathological psychiatric conditions, are crucially governed by the age at which the stress takes place. However, the cellular and molecular foundations for the impact of stress on neuronal function, and their change with age, are unknown. For example, it is not known whether 'psychological' stress signals are perceived by similar neuronal populations at different ages, and whether they activate similar or age-specific signaling pathways that might then mediate the spectrum of stress-evoked neuronal changes. We employed restraint and restraint/noise stress to address these issues in juvenile (postnatal day 18, [P18]) and adult rats, and used phosphorylation of the transcription factor CREB (pCREB) and induction of c-fos as markers of hippocampal neuronal responses. Stress-activated neuronal populations were identified both anatomically and biochemically, and selective blockers of the stress-activated hippocampal peptide, corticotropin-releasing hormone (CRH) were used to probe the role of this molecule in stress-induced hippocampal cell activation. Stress evoked strikingly different neuronal response patterns in immature vs adult hippocampus. Expression of pCREB appeared within minutes in hippocampal CA3 pyramidal cells of P18 rats, followed by delayed induction of Fos protein in the same cell population. In contrast, basal pCREB levels were high in adult hippocampus and were not altered at 10-120 min by stress. Whereas Fos induction was elicited by stress in the adult, it was essentially confined to area CA1, with little induction in CA3. At both age groups, central pretreatment with either a nonselective blocker of CRH receptors (alpha-helical CRH [9-41]) or the CRF1-selective antagonist, NBI 30775, abolished stress-evoked neuronal activation. In conclusion, hippocampal neuronal responses to psychological stress are generally more rapid and robust in juvenile rats, compared to fully mature adults, and at both ages, CRH plays a key role in this process. Enhanced hippocampal response to stress during development, and particularly the activation of the transcription factor CREB, may contribute to the enduring effects of stress during this period on hippocampal function.
Mol Psychiatry 2006 Nov
PMID:Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent. 1680 51

Myocardial ischemia provoked in the laboratory during mental stress (MSI) in patients with stable coronary artery disease (CAD) predicts subsequent clinical events. The pathophysiology of MSI differs from that of exercise ischemia, and the mechanisms tying MSI to poor prognosis are not known. C-reactive protein (CRP) is a risk marker for cardiovascular events in patients with CAD, but little is known regarding the relationship of CRP to MSI. The purpose of this study was to examine the association of CRP to risk of MSI in CAD patients. Eighty-three patients with stable CAD underwent simultaneous single-photon emission computed tomography (SPECT) imaging with technetium-99m tetrofosmin myocardial perfusion imaging (MPI) and transthoracic echocardiography (TTE), at rest and during MS induced by laboratory mental stress. Serum CRP levels were measured 24 h after MS. MSI was defined by the presence of a new perfusion defect on SPECT and/or new regional wall motion abnormality on TTE during MS. Of the 83 patients, 30 (36%) developed MSI. There was no difference in gender, sex, BMI, histories of diabetes, hypertension, smoking, lipid profile, medications used (including statins, beta-blockers, ACE inhibitors, and aspirin), or hemodynamic response during MS between those with and without MSI. In univariate logistic regression analysis, each unit (1 mg/L) increase in CRP level was associated with 20% higher risk of MSI (OR 1.2, 95% CI 1.01-1.39, P=.04). This relationship remained in multivariate models. These data suggest that levels of CRP may be a risk marker for MSI in patients with CAD.
Mol Med
PMID:C-reactive protein and vulnerability to mental stress-induced myocardial ischemia. 1738 Jan 91

Corticosterone (CORT) is seasonally modulated in many passerines, with plasma CORT concentrations lowest during the prebasic molt, when all feathers are replaced. Recent evidence indicating that CORT implants slow the rate of feather regrowth in molting birds suggests that plasma CORT concentrations are downregulated during molt in order to avoid the inhibition of feather growth caused by the protein catabolic activity of CORT. To further test this hypothesis, we examined whether endogenous CORT release, stimulated by exposure to either psychological stress or physical stress (food restriction), could inhibit feather regrowth rates or decrease feather quality in birds undergoing an induced molt (feather replacement after plucking). European starlings (Sturnus vulgaris) were exposed to chronic psychological stress or food restriction for three weeks of the feather regrowth period. Throughout this time, the length of growing primary, secondary, and tail feathers was measured and blood samples were collected to measure baseline and stress-induced CORT concentrations. Upon completion of growth, feather quality was analyzed via measurements of mass, rachis length, feather area, and presence of fault bars. Both psychological and physical stress protocols elevated circulating plasma CORT but significantly less than implants from an earlier study did. Psychological stress had no effect on feather regrowth rates or feather quality. Food restriction had no effect on feather growth rate but caused asynchronous feather replacement. When combined with psychological stress, physical stress also resulted in smaller feather area. Results indicate that CORT implants may not accurately represent chronic stress physiology. Additionally, the purpose for downregulating CORT concentrations during molt appears to be more complicated than simply protecting feather production from CORT's catabolic effects.
Comp Biochem Physiol A Mol Integr Physiol 2008 Jan
PMID:The effects of chronic psychological and physical stress on feather replacement in European starlings (Sturnus vulgaris). 1803 78

The psychobiological mechanisms that contribute to the development of stress resilience are not fully elucidated. One potential approach for enhancing resilience is the exposure to mild challenges. According to this approach, a mildly stressful episode may immunize the individual, thereby strengthening resistance to subsequent stressors. This phenomenon is often viewed as a form of behavioral immunization. Although, the term 'behavioral immunization' was borrowed from the field of immunology, the involvement of the adaptive immune system in stress resilience was never investigated. However, based on accumulated new data, we suggest that the immunological memory does have a significant role in developing coping responses to stress. Although, immune deficiency results in an impaired ability to cope with stress, boosting immunological memory can increase stress resilience. Therefore, we propose that defense against mental challenge, similarly to defense against intruders, involves an immunological mechanism, which establishes stress resilience to a later challenge. Here, we review the involvement of the adaptive immune system in coping mechanisms in response to psychological stress, and discuss the connection between cognitive memory and immunological memory in establishing ability to efficiently cope with stressful episodes.
Mol Psychiatry 2009 May
PMID:Behavioral immunization: immunity to self-antigens contributes to psychological stress resilience. 1877 18


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