The effect of d-amphetamine

can be antagonized by selective D(1)-like and 5-HT(2A) receptor antagonists. It is not known whether d-amphetamine’s PP2 datasheet effect requires an intact 5-hydroxytryptamine (5-HT) pathway.

The objective of this study was to examine the effects of d-amphetamine, quinpirole, and SKF-81297 on timing in intact rats and rats whose 5-hydroxytryptaminergic (5-HTergic) pathways had been ablated.

Rats were trained under the free-operant psychophysical procedure to press levers A and B in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic functions were fitted to the data for derivation of timing indices (T (50),

time corresponding to %B = 50%; Weber fraction). The effects of d-amphetamine (0.4 mg kg(-1) i.p.), quinpirole (0.08 mg kg(-1) i.p.), and SKF-81297 (0.4 mg kg(-1) s.c.) were compared between intact rats and rats whose 5-HTergic pathways had been destroyed by intra-raphe injection of 5,7-dihydroxytryptamine.

Quinpirole and SKF-81297 reduced T (50) in both groups; CAL101 d-amphetamine reduced T (50) only in the sham-lesioned group. The lesion reduced 5-HT levels by 80%; catecholamine levels were not affected.

d-Amphetamine’s effect on performance in the free-operant psychophysical procedure requires Selleckchem Selonsertib an intact 5-HTergic system. 5-HT, possibly acting at 5-HT(2A) receptors, may play a ‘permissive’ role in dopamine release.”
“Under physiological conditions, vasoconstrictors and vasodilators are counterbalanced. After aneurysmal subarachnoid hemorrhage (SAH) disturbance of this equilibrium may evoke delayed cerebral vasospasm (CVS) leading to delayed cerebral ischemia (DCI). Most studies examined either the vasoconstrictor endothelin-1 (ET-1) or the vasodilatiye pathway of nitric oxide (NO) and did not include investigations regarding the relationship between vasospasm and ischemia. Asymmetric dimethyl-L-arginine

(ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), decreases the concentration of NO. Studies have correlated increasing concentrations of ADMA with the course and degree of CVS after SAH. We sought to determine, if ADMA and endothelin-1 (ETA) are associated with CVS and/or DCI after SAH. CSF concentrations of ADMA and ET-1 were retrospectively determined in 30 patients after SAH and in controls. CVS was detected clinically and by arteriogaphy. DCI was monitored by follow-up Cl scans. 17 patients developed arteriographic CVS and 4 patients developed DCI. ADMA but not ET-1 concentrations were correlated with occurrence and degree of CVS. However, ET-1 concentrations were correlated with WFNS grade on admission. Neither ADMA nor ET-1 correlated with DCI in this cohort.

To elucidate the mechanism, the CA3 fungus was cultured under normoxic and hypoxic (ammonia fermenting) conditions, intracellular proteins were resolved by 2-DE, and 332 protein spots were identified using MALDI MS after tryptic digestion. Alcohol and aldehyde dehydrogenases that play key roles in oxidizing ethanol were produced at the basal level under hypoxic conditions but were obviously provoked by ethanol under normoxic conditions. Enzymes involved in gluconeogenesis, as well as the tricarboxylic and glyoxylate cycles, were downregulated. These results indicate that the mechanism of fungal energy conservation is altered under hypoxic conditions. The results also showed that proteins in the pentose phosphate pathway

as well as the metabolism of both nucleotide and thiamine were upregulated under hypoxic conditions. Levels of xanthine GW786034 in vivo and hypoxanthine, deamination products of guanine and adenine were increased in DNA from hypoxic cells, indicating an association between hypoxia and intracellular DNA base damage. This study is the first proteomic comparison of the hypoxic responses of A. nidulans.”
“Parkinson’s disease has been found to impair comprehension of complex sentences. Here we follow up on earlier findings that sentences describing two successive events in the

form of “”Before B, A”" are understood worse by Parkinson patients than sentences in the form of “”After A, B”". Before-initial sentences express events in an order inconsistent with their actual order of occurrence and therefore require additional computations during comprehension. In a behavioral Oxalosuccinic acid study we tested whether 28 German Parkinson patients reading ‘before’- and ‘after’-initial sentences correctly understood the sequence of events. A second functional magnetic resonance imaging study investigated 16 different patients who read sentences while in the scanner. The behavioral study revealed that ‘before’ sentences were misunderstood with regard to the temporal sequence of events in 53% (controls 6.5%). The imaging

study demonstrated a functional network of the caudate nucleus, middle frontal gyrus, medial superior frontal gyrus, parietal lobule and inferior temporal gyrus. This network was dynamically modulated for ‘before’ compared to ‘after’ sentences in healthy controls but not in Parkinson patients. The current results suggest that the additional computations required for ‘before’ sentences are supported by a network with the caudate nucleus as a central element. This network was compromised in Parkinson patients. We propose that dysfunction of the caudate nucleus networks underlies Parkinson patients’ difficulty in dealing with complex sentence structures. (C) 2012 Elsevier Ltd. All rights reserved.”
“It is well known that infectious and inflammatory diseases such as sepsis and severe inflammatory response syndrome are accompanied by metabolic alterations such as insulin resistance.

Sorting these libraries by FACS for binders against HER2/neu yielded antigen-specific

Fc binders (Fcab; Fc antigen binding) of which one was affinity matured, resulting in Fcab clone H10-03-6 which showed >10-fold improvement in antigen-binding activity versus Selleckchem GSK126 the parental clone. Pre-equilibrium surface plasmon resonance experiments revealed a K(D) value of 69 nM. H10-03-6 did not react with other members of the HER family and specifically interacted with HER2-positive but not with HER2-negative cells. Importantly, Fcab H10-03-6 elicited potent antibody-dependent cellular cytotoxicity in vitro. Finally, the in vivo half-life in mice was similar to wild-type Fc indicating that the amino acid changes in the CH3 domain did not affect the pharmacokinetic behavior

of the recombinant Fc. Our data demonstrate that the Fcab scaffold combines all features of normal antibodies in a small 50 kD homodimeric protein: antigen binding, effector functions and long half-life in vivo.”
“Introduction: N-(2-tert-butyl-14 (4,4-difluorocyclohexyl)methyl)-1 H-benzo[d]imidazol-5-yl)ethanesulfonamide (AZD1940) is a candidate drug for treatment of neurepathic pain. As part of the preclinical evaluation of AZD1940, a microdosing study with positron emission tomography (PET) was conducted to assess brain exposure.

Methods: AZD1940 was radiolabeled with carbon-11 in the benzimidazole moiety. The radioactive precursor, lithium [C-11]pivalate

was obtained via C-11-carboxylation of tert-butyl lithium. The target compound, Pexidartinib solubility dmso [C-11]AZD1940, was in turn obtained by the microwave assisted reaction between lithium [11C]pivalate and the o-phenylene diamine analog of AZD1940 (N-(3-amino-44(4,4-difluorocyclohexlmethylamino)phenylethanesulfonamide) selleck chemical in neat phosphorous oxychloride. A brain PET measurement was performed in cynomolgus monkey.

Results: The overall radiochemical yield of final formulated radiochemically pure (>99%) [C-11]AZD1940 was 0.4% (uncorrected for decay) and the specific radioactivity was 13 GBq/mu mol at time of administration (58 min after end of bombardment). After intravenous injection to cynomolgus monkey, the maximum concentration of radioactivity detected in the brain region of interest was 0.7% of the total injected radioactivity. The regional distribution of radioactivity within brain was homogenous.

Conclusions: AZD1940 was radiolabelled with carbon-11 and its brain exposure, assessed using PET, was relatively low in comparison to peripheral organ exposure. (C) 2013 Elsevier Inc. All rights reserved.”
“Expression of the transcription repressor Gfi-1 is required for the maintenance of murine hematopoietic stem cells. In human cells, ectopic expression of Gfi-1 inhibits and RNA interference-mediated Gfi-1 downregulation enhances proliferation and colony formation of p210BCR/ABL expressing cells.

The prevalence of sign epistasis for fitness-related biochemical phenotypes

has AG-014699 price important implications for the evolutionary dynamics of protein polymorphism in natural populations.”
“The Root effect is a pH-dependent reduction in hemoglobin-O-2 carrying capacity. Specific to ray-finned fishes, the Root effect has been ascribed specialized roles in retinal oxygenation and swimbladder inflation. We report that when rainbow trout are exposed to elevated water carbon dioxide (CO2), red muscle partial pressure of oxygen (PO2) increases by 65%-evidence that Root hemoglobins enhance general tissue O-2 delivery during acidotic stress. Inhibiting carbonic anhydrase (CA) in the plasma abolished this effect. We argue that CA activity in muscle capillaries short-circuits red blood cell (RBC) pH regulation. This acidifies

RBCs, unloads O-2 from hemoglobin, and elevates tissue PO2, which could double O-2 delivery with no change in perfusion. This previously undescribed mechanism to enhance O-2 delivery during stress may represent the incipient function of Root hemoglobins in fishes.”
“Several progeroid disorders, including Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (ZMPSTE24 deficiency), arise when a farnesylated and methylated form of prelamin A accumulates at the nuclear envelope. Here, we found that a hypomorphic allele of isoprenylcysteine carboxyl methyltransferase (ICMT) increased body

weight, normalized grip strength, and prevented bone fractures and cAMP activator inhibitor death in Zmpste24-deficient mice. The reduced ICMT activity caused prelamin A mislocalization within the nucleus and triggered prelamin A-dependent activation of AKT-mammalian target of rapamycin (mTOR) signaling, which abolished the premature senescence of Zmpste24-deficient fibroblasts. ICMT inhibition increased AKT-mTOR signaling and proliferation and delayed senescence in human HGPS fibroblasts but did not reduce the levels of misshapen nuclei VX-661 concentration in mouse and human cells. Thus, targeting ICMT might be useful for treating prelamin A-associated progeroid disorders.”
“Below a certain level, table salt (NaCl) is beneficial for animals, whereas excessive salt is harmful. However, it remains unclear how low- and high-salt taste perceptions are differentially encoded. We identified a salt-taste coding mechanism in Drosophila melanogaster. Flies use distinct types of gustatory receptor neurons (GRNs) to respond to different concentrations of salt. We demonstrated that a member of the newly discovered ionotropic glutamate receptor (IR) family, IR76b, functioned in the detection of low salt and was a Na+ channel. The loss of IR76b selectively impaired the attractive pathway, leaving salt-aversive GRNs unaffected. Consequently, low salt became aversive.

“
“Although several molecular and genetic manipulations may produce hyperactive animals, hyperactivity alone is insufficient for the animal to qualify as a model of ADHD. Based on a wider range of criteria behavioral, genetic and neurobiological – the spontaneously learn more hypertensive rat (SHR)

obtained from Charles River, Germany (SHR/NCrl) at present constitutes the best validated animal model of ADHD combined subtype (ADHD-C), and the Wistar Kyoto substrain obtained from Harlan, UK (WKY/NHsd) is its most appropriate control. Although other rat strains may behave like WKY/NHsd rats, genetic results indicate significant differences when compared to the WKY/NHsd substrain, making them less suitable controls for the SHR/NCrl, The use of WKY/NCrl, outbred Wistar, Sprague Dawley or other rat strains as controls for SHRs may produce spurious neurobiological differences. Consequently data may be mis, interpreted if insufficient care is taken in the selection of the control group. It appears likely that the use of different control strains may underlie some of the discrepancies

in results and interpretations in studies involving the SHR and WKY. Finally, we argue that WKY rats obtained from Charles River, Germany (WKY/NCrl) provide a promising model for the predominantly inattentive subtype of ADHD (ADHD-PI); in this case also the WKY/NHsd substrain should be used as control. (C) 2009 Elsevier Ltd. All rights reserved.”
“We compared the performance

of Bayesian learning strategies and approximations to such strategies, which are far less computationally demanding, in a setting requiring Selleck FRAX597 individuals to make binary decisions based on experience. Extending Bayesian updating schemes, we compared the different strategies while allowing for various implementations of memory and knowledge about the environment. The dynamics of the observable variables was modeled through basic probability distributions and convolution. This theoretical framework was applied to the problem of male fruit flies who have to decide which females they should www.selleck.cn/products/MS-275.html court. Computer simulations indicated that, for most parameter values, approximations to the Bayesian strategy performed as well as the full Bayesian one. The linear approximation, reminiscent of the linear operator, was notably successful, and, without innate knowledge, the only successful learning strategy. Besides being less demanding in computation and thus realistic for small brains, the linear approximation was also successful at limited memory, which would translate into robustness in rapidly changing environments. Knowledge about the environment boosted the performance of the various learning strategies with maximal performance at large utilization of memory. Only for limited memory capacities, intermediate knowledge was most successful.

Conclusions: Four common methods for calculating hospital-wide mortality produced substantially different results. This may have resulted from a lack of standardized national eligibility and exclusion

criteria, different statistical methods, or fundamental flaws in the hypothesized association between hospital-wide mortality and quality of care. (Funded by the Massachusetts Division of Health Care Finance and Policy.)

N Engl J Med 2010;363:2530-9.”
“Objective: Buparlisib mw This study examined the national use of vena cava filters (VCFs) from 1998 to 2005.

Methods: Methods for complex surveys were used to examine hospital discharge data from the Nationwide Inpatient Sample (NIS) to determine the use of VCFs for the years 1998

to 2005. VCF placement in the absence of deep venous thrombosis (DVT) or pulmonary embolus (PE) was categorized as prophylactic.

Results: During the study period, the estimated rate of hospitalizations per year with a diagnosis of DVT (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.019-1.032; P < .01) or PE (OR, 1.076; 95% CI, 1.069-1.083; P < .01) rose significantly. The estimated weighted frequency PS-341 concentration of VCF placement increased from 52,860 procedures in 1998 to 104,114 procedures in 2005 (0.15% and 0.27% of all discharges, respectively), representing an 80% increase. VCF placement significantly increased during hospitalizations with any diagnosis of DVT or PE, or both, and no DVT or PE (P < .01 for each). Logistic regression models revealed that the rate of prophylactic VCF placement increased at a significantly higher rate than VCF placement associated with DVT or PE (157% vs 42%; P < .01), after adjusting for age, gender, and hospital characteristics. Prophylactic VCF placement in the setting of morbid obesity (P <.01) and head injury (P = .03) rose significantly over time.

Conclusions: From 1998 to 2005, the estimated rates of prophylactic

VCF placement increased at a significantly higher rate than VCF placement in the setting of DVT or PE. Significant increases in the use of prophylactic VCFs were seen in the setting of morbid obesity buy CB-839 and head injury. (J Vase Surg 2010;52:118-26.)”
“Objective: While much attention has been devoted toward treatment paradigms for idiopathic axillo-subclavian vein thrombosis (ASVT), little has focused on long-term durability of aggressive treatment and its associated functional outcomes. The purpose of this study was to review our own surgical therapeutic algorithm and its associated durability and functional outcomes.

Methods: All patients treated with combined endovascular and open surgery at Dartmouth-Hitchcock Medical Center for ASVT from 1988 to 2008 were identified. Patient demographics, comorbidities, and operative techniques were recorded.

Investigators and participants were masked to treatment assignment. The primary endpoint was change in NT-proBNP, a marker of left ventricular wall stress, from baseline to 12 weeks; analysis included all patients randomly assigned to treatment groups who had a baseline and at least one postbaseline assessment.

This trial is registered at Clinicaltrials.gov, number NCT00887588.

Findings 149 patients were randomly assigned to LCZ696 and 152 to valsartan; 134 in the LCZ696 group and 132 in the valsartan group were included in analysis of the primary endpoint. NT-proBNP was significantly reduced at 12 weeks in the LCZ696 group compared with the valsartan group (LCZ696: baseline, 783 Daporinad pg/mL [95% CI 670-914], 12 weeks, 605 pg/mL [512-714]; valsartan: baseline, 862 pg/mL [733-1012], 12 weeks, 3-deazaneplanocin A price 835 [710-981]; ratio LCZ696/valsartan, 0.77, 95% CI 0.64-0.92, p=0.005). LCZ696 was well tolerated with adverse effects similar to those of valsartan; 22 patients (15%) on LCZ696 and 30 (20%) on valsartan had one or more serious adverse event.

Interpretation In patients with heart failure with preserved ejection fraction, LCZ696 reduced NT-proBNP to a greater extent than did valsartan at 12

weeks and was well tolerated. Whether these effects would translate into improved outcomes needs to be tested prospectively.”
“Reactive oxygen species (ROS) are believed to be involved in many forms of neurodegeneration, including ischaemic infarct damage and Alzheimer’s disease. Despite the known involvement of p38 and JNK MAP kinases in mediating apoptosis and cell death in a variety of cell types, the details of the signalling pathways activated in neuronal cells by ROS are poorly characterised. Recently TAK1 (MAP3K7), a kinase upstream of JNK and p38, has attracted attention as a possible mediator of ischaemic cell death. This study tested the hypothesis that hydrogen

peroxide (H2O2), which produces ROS, induces apoptosis in the NG108-15 neuronal cell line via activation of either TAXI or the related kinase ASK1 (MAP3K5). H2O2 caused a concentration-dependent reduction in cell viability associated with caspase 3 activation. Loss of cell viability was inhibited by a selective caspase 3 inhibitor, and by the p38 inhibitor SB203580, this website but was not affected by the JNK inhibitor SP600125. The selective TAK1 inhibitor 5Z-7-oxozeaenol (5Z-7) exacerbated the loss of cell viability, whereas the ASK1 inhibitor NQDI-1 completely prevented caspase activation and cell death. These results show that pharmacological inhibition of ASK1 is neuroprotective, implicating an ASK1-p38 signalling pathway in ROS-induced apoptosis in neurones. The results also imply that the role of TAK1 may be neuroprotective rather than pro-degenerative. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Objectives Several studies have suggested insulin resistance related to dyslipidemia and body weight in drug treated schizophrenia patients.

In addition, a history of chronic or traumatic stress exposure is a predisposing risk factor. We have developed a Chronic plus Acute Prolonged

Stress (CAPS) treatment for rats that models some of the characteristics of stressful events that can lead to PTSD in humans. We have previously shown that CAPS enhances acute fear responses and impairs selleck kinase inhibitor extinction of conditioned fear. Further, CAPS reduced the expression of glucocorticoid receptors in the medial prefrontal cortex. In this study we examined the effects of CAPS exposure on behavioral stress coping style, anxiety-like behaviors, and acute stress reactivity of the hypothalamic pituitary adrenal (HPA) axis. Male Sprague-Dawley rats were exposed to CAPS treatment, consisting of chronic intermittent cold stress (4 degrees C, 6 h/day, 14,days) followed on day 15 by a single 1-h session of sequential acute stressors (social defeat, immobilization, swim). After

CAPS or control treatment, different groups were tested for shock probe defensive burying, novelty Selleckchem Copanlisib suppressed feeding, or evoked activation of adrenocorticotropic hormone (ACTH) and corticosterone release by an acute immobilization stress. CAPS resulted in a decrease in active burying behavior and an increase in immobility in the shock probe test. Further. CAPS-treated rats displayed increases in the latency to feed in the novelty suppressed feeding test, despite an increase in food intake in the home cage. CAPS treatment also reduced the HPA response to a subsequent acute immobilization stress. These results further validate CAPS treatment as a rat model of relevance to PTSD, and together with results reported previously, suggest that CAPS impairs fear extinction, shifts coping behavior from an active to a more passive strategy, increases anxiety, and alters HPA reactivity, resembling many aspects of human PTSD. (C) 2012 Elsevier PCI-34051 research buy Ltd. All rights reserved.”
“A medication error is a failure in the treatment process that

leads to, or has the potential to lead to, harm to the patient. Medication errors can occur in deciding which medicine and dosage regimen to use (prescribing faults-irrational, inappropriate, and ineffective prescribing, underprescribing, overprescribing); writing the prescription (prescription errors); manufacturing the formulation (wrong strength, contaminants or adulterants, wrong or misleading packaging); dispensing the formulation (wrong drug, wrong formulation, wrong label); administering or taking the medicine (wrong dose, wrong route, wrong frequency, wrong duration); monitoring therapy (failing to alter therapy when required, erroneous alteration). They can be classified, using a psychological classification of errors, as knowledge-, rule-, action- and memory-based errors. Although medication errors can occasionally be serious, they are not commonly so and are often trivial.

Conclusions: In hemodialysis patients, the fragments NT-proBNP and MR-pro-ANP are largely elevated compared to BNP which is explained by accumulation. The prognostic performance of MR-pro-ANP is similar to that of NT-proBNP or BNP. Copyright (c) 2012 S. Karger AG, Basel”
“Advancements in human genetics now poise the field to illuminate the pathophysiology of complex genetic disease. In particular, genome-wide association studies (GWAS) have generated insights into the mechanisms driving inflammatory bowel disease (IBD) and implicated genes shared by multiple autoimmune and autoinflammatory diseases. Thus, emerging evidence suggests a central

Selleckchem MK-8931 role for the mucosal immune system

in mediating immune homeostasis and highlights the complexity of genetic and environmental interactions that collectively modulate the risk of disease. Nevertheless, the challenge remains to determine how genetic variation can precipitate and sustain the inappropriate inflammatory response to commensals that is observed in IBD. Here, we highlight recent advancements in immunogenetics and provide a forward-looking view of the innovations that will deliver mechanistic insights from human genetics.”
“Methamphetamine (METH) is a new type of drug with strong tolerance and addiction. However, the molecular mechanisms underlying the processes of METH addiction are still not fully understood. DAPT concentration To determine possible biomarkers and mechanisms that are responsible for METH addiction, a 2-DE based proteomics approach was used to evaluate the changes in protein expression of the serum in Chinese patients addicted to METH, which to the best of our knowledge is the first study of its kind. We identified five proteins that were markedly altered and complement factor H (CFH), the most stably up-expressed protein in each 2-DE experiment, was further studied using the rat conditioned place preference (CPP) model to detect any changes

to its expression in the sera and six brain C1GALT1 regions of interest. We report, for the first time, that CFH was positive related to METH addiction. (c) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Ultrasound vocalizations (USVs) at approximately 22 kHz are usual components of the defensive response of rats. However, depending on the neural substrate that is activated, such as the dorsal periaqueductal gray (dPAG), USV emissions may be reduced. Activation of neurokinin-1 (NK-1)-mediated mechanisms of the dPAG causes analgesia, reduced 22 kHz USVs, and anxiogenic-like effects in rats exposed to the elevated plus maze (EPM). Involvement of other types of neurokinin receptors in this activation has not yet been evaluated.

The present study examined whether local injections of the selective NK-3 agonist senktide (1-100 pmol/0.

It is not known, however, if noradrenergic modulatory function is compromised by chronic stress, perhaps contributing to the stress-induced cognitive deficit. Thus, the first study investigated whether acutely elevating noradrenergic activity in mPFC still enhances cognitive function after chronic stress. As previously demonstrated, CUS impaired cognitive set-shifting on the AST.

This deficit was abolished by acute systemic administration of the alpha(2)-adrenergic autoreceptor antagonist, atipamezole. Microdialysis revealed no differences in extracellular norepinephrine (NE) levels in mPFC of CUS-exposed and unstressed control rats at baseline or during behavioral testing, and comparable increases after atipamezole. In the second experiment, rats were treated chronically with the selective NE reuptake MDV3100 ic50 blocker, desipramine, during the CUS treatment through behavioral testing. Again. CUS impaired cognitive set-shifting Verubecestat in vehicle-treated rats, and chronic desipramine treatment prevented

such deficits. Acute blockade of post-synaptic alpha(1)-adrenergic receptors in mPFC prior to testing blocked the beneficial effect of desipramine on cognitive set-shifting. These results suggest that desipramine restores cognitive set-shifting capability that has been compromised by chronic stress by activating alpha(1)-adrenergic receptors in the mPFC. Thus, noradrenergic modulatory capability in mPFC remains intact after CUS, and this represents one possible substrate by which antidepressants may exert their beneficial effects in the treatment

of depression. (C) 2010 Elsevier Inc. All rights reserved.”
“Chronic psychosocial isolation stress (CPSI) modulates glucocorticoid receptor else (GR) functioning in Wistar male rat hippocampus (HIPPO) through alteration of nuclear GR phosphorylation and its upstream kinases signaling, which parallels animal depressive-like behavior. The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine (FLU) on GR signaling in HIPPO and depressive-like behavior in CPSI animals.

FLU was administrated to female and male naive or CPSI rats for 21 days and GR protein, its phosphorylation status and upstream kinases, as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone (CORT) and depressive-like behavior.

The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232-Cdk5 pathway and JNK signaling in a gender-specific way. In contrast, in both genders CPSI increased the nuclear levels of GR and pGR246 but decreased CORT and mRNA levels of GR and BDNF.