Based on the analyses classified by best-stimulus categories, the number of NaCl-best neurons decreased from 68% to 45% following dietary sodium deprivation, and the responses of the NaCl-best neurons to 0.03-1.0 M NaCl were significantly inhibited. Multidimensional scaling illustrated that sodium deprivation increased the similarity of the response profiles of the NaCl-best neurons. These findings suggest that dietary sodium

deprivation might modulate sodium intake via increasing aversive threshold for salt rather enhancing salt discrimination. (C) 2008 Published by Elsevier Ireland Ltd.”
“The protein encoded by the UL14 gene of herpes simplex virus type 1 (HSV-1) and HSV-2 is expressed late in infection and is a minor component of the virion tegument. An UL14-deficient HSV-1 see more mutant (UL14D) forms small plaques and exhibits an extended growth cycle LEE011 mouse at

low multiplicities of infection (MOI) compared to wild-type virus. Although UL14 is likely to be involved in the process of viral maturation and egress, its precise role in viral replication is still enigmatic. In this study, we found that immediate-early viral mRNA expression was decreased in UL14D-infected cells. Transient coexpression of UL14 and VP16 in the absence of infection stimulated the nuclear accumulation of both proteins. We intended to visualize the fate of VP16 released from the infected virion and constructed UL14-null (14D-VP16G) and rescued (14R-VP16G) viruses that expressed a VP16-green fluorescent protein (GFP) fusion protein. Synchronous high-multiplicity infection of the viruses was performed at 4 degrees C in the absence of de novo protein synthesis. We found that the presence of UL14 in the virion had an enhancing effect on the nuclear accumulation of VP16-GFP. The lack of UL14 did not significantly alter virus internalization but affected incoming capsid transport to the nuclear pore. These observations suggested that UL14 (i) enhanced VIP16 nuclear localization at the immediately early phase, thus indirectly regulating the expression of immediate-early genes, and (ii) was associated with efficient nuclear targeting of capsids.

The next tegument protein UL14 could be part of the machinery that regulates HSV-1 replication.”
“The present study tested the hypothesis that the hypoxia in utero results in decreased protein tyrosine phosphatase (PTP) activity in cytosolic and membrane fractions and increased expression of PTPs (PTP-1B, PTP-SH1 and PTP-SH2) in the cytosol and the membrane fraction of the cerebral cortex of guinea pig fetus. In addition, we hypothesize that the increased expression is mediated by nitric oxide (NO). To test this hypothesis, PTP activity in cytosol and cell membrane, and expression in the cytosol and membrane fraction were measured in the cerebral cortex of normoxic, hypoxic and L-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), pretreated hypoxic (L-NAME + Hx) guinea pig fetuses.

Furthermore, Ucn1 mRNA in males was nearly 10 times and 1.6 times higher than in females in di-and pro-estrus, respectively, indicating a sex-dependent difference in Ucn1 biosynthetic activity. Since, at the same time, immunocytochemistry revealed that the amount of Ucn1 peptide stored in the cell bodies of the npEW-Ucn1 neurons did not differ between males and females, as judged on the basis of the number and immunosignal density of these neurons, we propose that the rate of axonal Ucn1 transport and, possibly, the strength of Ucn1 secretion, are dependent on sex to the same degree

as is Ucn1 biosynthesis. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the selective loss of

dopaminergic neurons and the presence of Lewy bodies. alpha-Synuclein is a major component of Lewy buy S63845 bodies. Recently, many studies have focused on the interaction between alpha-synuclein and catecholamine in the pathogenesis of PD. However, no detailed relationship between cathecholamine and alpha-synuclein cytotoxicity has been elucidated. Therefore, this study established PC12 cell lines which overexpress human alpha-synuclein in a tetracycline-inducible manner. buy PRI-724 The overexpression of human alpha-synuclein increased the number of apoptotic cells in a long-term culture. Moreover, human alpha-synuclein expressing PC12 cells demonstrated an increased vulnerability to several stressors in a short culture period. Thapsigargin increased the SIDS soluble oligomers of alpha-synuclein associated with catecholamine-quinone. The unfolded protein response (UPR) study showed that thapsigargin

increased eIF2 alpha phosphorylation and nuclear GADD153/CHOP induction under alpha-synuclein overexpressed conditions. The activities of the ATF6 alpha and IRE1 alpha pathways Galeterone decreased. These findings suggest that an overexpression of alpha-synuclein partly inactivates the UPR. alpha-Methyltyrosine inhibited the dysfunction of the UPR caused by an overexpression of human alpha-synuclein. Therefore, these findings suggest that the coexistence of human alpha-synuclein with catecholamine enhances the endoplasmic reticulum stress-related toxicity in PD pathogenesis. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Neuronal intranuclear inclusions (NIIs) are the pathological hallmark of polyglutamine (polyQ) diseases. We previously found that the RNA-binding protein FUS/TLS is the major component of nuclear polyQ aggregates of a cellular model of Huntington disease. In this study, we revealed that FUS/TLS binds to NIIs in the human brains from patients with spinocerebellar ataxia type 1, 2, 3, and dentatorubral-pallidoluysian atrophy. Recent reports have revealed that mutations in FUS/TLS gene are responsible for familial amyotrophic lateral sclerosis 6 (ALS6).

The presence of accessory renal arteries, solitary kidneys, or renal fibromuscular dysplasia had no influence on overall accuracy of using PSV values for detecting >= 60% stenosis.

Conclusions: A PSV of 285 cm/s or an RAR of 3.7 alone can be used in detecting >= 60% RAS. Previously published data must be validated in individual vascular laboratories. (J Vasc Surg 2012;56:1052-60.)”
“Recent neuroimaging studies suggest that Idasanutlin price prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition,

with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual selleck cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer’s disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition

across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Erastin purchase Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests

that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of categorical knowledge. (c) 2013 Elsevier Ltd. All rights reserved.”
“Ribosomes occupy a central position in cellular metabolism, converting stored genetic information into active cellular machinery. Ribosomal proteins modulate both the intrinsic function of the ribosome and its interaction with other cellular complexes, such as chaperonins or the signal recognition particle.

The clinical feasibility of this approach Fulvestrant in vivo was evaluated in 5 cases of lesion resection. In addition, system performance was evaluated by measuring the latency between surgical tool tracking and visualization of the seeded WM tracts.

RESULTS: Lesion resection was performed successfully in all 5 patients. The seeded WM tracts close to the lesion and other critical structures, as defined by the functional and structural images, were interactively visualized during the intervention to determine their spatial relationships relative to the lesion and critical cortical areas. Latency between

tracking and visualization of tracts was less than a second for a fiducial radius size of 4 to 5 mm.

CONCLUSION: Interactive tractography can provide an intuitive way to inspect critical WM tracts in the vicinity of the surgical region, allowing the surgeon

to have increased intraoperative WM information to execute the planned surgical resection.”
“Aim:

The aim of this study was to quantitatively and qualitatively assess the effect of sample storage on the metabolically active microbial community found in sputum samples from patients with cystic fibrosis (CF).

Methods:

Sputum samples were collected and split in two equal aliquots one of which was immersed in RNAlater and refrigerated immediately, the second stored at room temperature for 24 h and RNAlater Quizartinib cost was subsequently added. mRNA was extracted, and RT-PCR-DGGE and qPCR analysis of the bacterial and fungal communities was carried out.

Results:

Significant differences in the bacterial communities between the two protocols were observed but there were no significant difference seen in the fungal community analyses. Analysis by qPCR demonstrated that room temperature storage gave statistically significant increases in eubacteria and Pseudomonas spp. and a statistically significant decrease in those of Haemophilus influenzae.

Conclusions:

The analysis of metabolically active microbial communities from CF sputum using molecular techniques indicated that samples should be stored at 4 degrees C upon addition of RNAlater to obtain Resveratrol an accurate depiction of

the CF lung microbiota. Also, storing respiratory samples at room temperature may cause an over representation of Pseudomonas aeruginosa and mask the presence of other clinically significant organisms.”
“Traumatic cerebrovascular injury (TCVI) is present in approximately 1% of all blunt force trauma patients and is associated with injuries such as head and cervical spine injuries and thoracic trauma. Increased recognition of patients with TCVI in the past quarter century has been because of aggressive screening protocols and noninvasive imaging with computed tomography angiography. Extracranial carotid and vertebral artery injuries demonstrate a spectrum of severity, from intimal disruption to traumatic aneurysm formation or vessel occlusion.

Magnetic resonance imaging on admission showed variable wall thickening of the arachnoid cyst with mild mass effect on the left frontotemporal lobes.

INTERVENTION: The patient underwent decompression of the arachnoid cyst and biopsy of the cyst wall. Histologic and immunohistochemical

studies of the thickened portion initially suggested a metastatic carcinosarcoma, but fluorescence in situ hybridization (FISH) studies confirmed the diagnosis of anaplastic meningioma based on characteristic chromosomal deletions. The patient returned 2 months later with progressive disease, leading to his death 6 weeks later despite repeat surgery for tumor debulking.

CONCLUSION: Malignant transformation of meningothelial Elacridar elements in arachnoid cysts is an exceptionally rare complication that poses considerable diagnostic challenges. Genetic markers may be particularly helpful in such cases.”
“Background:

Lower extremity arterial revascularization (LEAR) is the gold-standard for critical lower limb ischemia (CLI). The goal of this study was twofold. First, we evaluated the long-term functional status of patients undergoing primary LEAR for CLI. Second, prognostic factors of long-term functional status and survival after primary LEAR for CLI were assessed.

Methods: All primary LEAR procedures were analyzed. Patients were stratified by preoperative Fedratinib cost functional status: ambulatory (group I) vs nonambulatory (group II). Liothyronine Sodium Patients were followed-up after 3 and 6 years. Adverse events (AEs) were categorized

according to predefined standards: minor, surgical, failed revascularization, and systemic. Associated patient demographic/clinical data were analyzed using univariate and multivariate methods.

Results: There were 106 LEAR patients (group I: n = 42, 40% vs group II: n = 64, 60%). Group II patients were significantly older (75 vs 62 years; P=.00), were classified ASA 3-4 more frequently (78% vs 52%; P<.02), had more cardiac disease (n = 42, 66% vs n = 10, 24%; P=.00), renal disease (n = 26, 41% vs n = 7, 17%; P=.00), diabetes (11 = 36, 56% vs n = 8, 19%; P=.00), hypertension (n = 47, 73% vs n = 13, 31%; P=.00) and severe CLI (n = 42, 66% vs n = 18, 38%; P<.01). Group II patients had a higher incidence of death (65.6% vs 14.3%; P=.00), minor AEs (n = 38, 26% vs n = 10, 22%; P=.00), surgical AEs (n = 48, 33% vs n = 12, 26%; P<.02) and systemic AEs (n = 24, 86% vs n = 4, 9%; P<.02). Also more unplanned reinterventions occurred in group 11 (n = 148, 76% vs n = 47, 24%; P=.00). Nonambulatory status was a multivariate independent predictor of nonambulatory status after LEAR during 6 years follow-up (odds ration [OR[: 21.47; 95% confidence interval [CI]: 2.76-166.77; P=.00). Pulmonary disease (OR: 7.49; 95% CI: 2.17-25.80; P=.00), not prescribing beta-blockers (OR: 4.67; 95% Cl: 1.28-17.03; P<.02), nonambulator-, status (OR: 22.99; 9.5% CI: 6.27-84.24; P=.00), and systemic AEs (OR: 9.66; 95% CI: 1.84-50.57; P<.

“
“Recent functional

neuroimaging studies have suggested that specific brain regions might be associated with the formation of anxiety-related personality traits, which are well known to be influenced by gender. Such anxiety-related personality traits are one of the representative predisposing factors for mood and anxiety disorders, whose incidence is also known to be much influenced by gender. However, little is known about the gender differences in brain function related to anxiety-related personality traits. The aim of the present study was to examine gender-related differences in the pattern of the relationships between an anxiety-related Nepicastat clinical trial personality trait and cerebral brain glucose metabolism. Regional brain glucose metabolism was measured using [(18)F]fluorodeoxyglucose positron emission tomography in 102 healthy subjects (65 males and 37 females). An anxiety-related trait was assessed using the Temperament and Character Inventory dimension Harm Avoidance (HA). HA was negatively correlated with glucose metabolism in the anterior portion of the ventromedial prefrontal

cortex (vmPFC) in females but not in males. The anterior vmPFC may be a possible neural target for the prevention or therapy of emotional disorders, especially in females. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: We studied the safety and efficacy of multiple adjuvant apaziquone instillations in patients with high risk nonmuscle invasive RNA Synthesis inhibitor bladder cancer.

Materials and Methods: Patients with high risk

nonmuscle invasive urothelial carcinoma of the bladder underwent transurethral resection of all bladder tumor(s), and received 6 weekly adjuvant intravesical apaziquone Tyrosine-protein kinase BLK instillations of 4 mg in 40 ml. Patients with carcinoma in situ received 3 further maintenance instillations at months 3, 6 and 12. Followup consisted of cystoscopy, urine cytology and observation of adverse events every 3 months for 18 months.

Results: A total of 53 patients were enrolled in the study. Although all patients were high risk according to the definitions used when the study was initiated, according to most recent guideline criteria, 80% and 20% of these patients would now be considered intermediate and high risk for recurrence, and 50% and 44% would be considered intermediate and high risk for progression, respectively. Intent to treat analysis of 49 patients with papillary tumors showed recurrent tumors in 34.7% and 44.9% at 12 and 18 months, respectively. One patient had progression to T2 or greater urothelial carcinoma after 9 months. There were 4 patients with carcinoma in situ who had complete responses at 3 months but discontinued treatment due to cystitis, recurrent papillary disease, urinary incontinence and dysuria. Most other side effects were mild (grade 1 to 2).

Conclusions: Adjuvant intravesical instillations of apaziquone are generally well tolerated. The recurrence rates of 34.7% after 12 months and 44.

By mutagenesis of the Con-1 replicon, we show that disruption of this alternative pairing inhibited replication, a phenotype that could be restored to wild-type levels through the introduction STI571 supplier of compensating mutations in the upstream region. Substitution of the CRE with the analogous region of different genotypes of HCV produced replicons with phenotypes consistent with the hypothesis that both local and long-range interactions are critical for a fundamental aspect of genome replication. This report

further extends the known interactions of the SL9266 CRE, which has also been shown to form a “”kissing loop”" interaction with the 3 ‘ NCR (P. Friebe, J. Boudet, J. P. Simorre, and R. Bartenschlager, J. selleck chemicals Virol. 79: 380-392, 2005), and suggests that cooperative long-range binding with both 5 ‘ and 3 ‘ sequences stabilizes the CRE at the core of a complex pseudoknot. Alternatively, if the long-range interactions

were mutually exclusive, the SL9266 CRE may function as a molecular switch controlling a critical aspect of HCV genome replication.”
“Enzootic nasal tumor virus (ENTV) is a close relative of jaagsiekte sheep retrovirus (JSRV), and the two viruses use the same receptor, hyaluronidase 2 (Hyal2), for cell entry. We report here that, unlike the JSRV envelope (Env) protein, the ENTV Env protein does not induce cell fusion at pHs of 5.0 and above but requires a much lower pH (4.0 to 4.5) for fusion to occur. The entry of ENTV Env pseudovirions was substantially inhibited by bafilomycin A1 (BafA1) but was surprisingly enhanced by lysosomotropic agents and lysosomal protease inhibitors following a 4- to 6-h treatment period; of note, prolonged treatment with BafA1 or ammonium chloride completely blocked ENTV entry. Unlike typical pH-dependent viruses,

ENTV Env pseudovirions were virtually resistant to inactivation at a low pH (4.5 or 5.0). Using chimeras formed from ENTV and JSRV Env proteins, we demonstrated that the transmembrane (TM) subunit of ENTV Env is primarily responsible for its unusually low pH requirement for fusion but found that the surface (SU) subunit of ENTV Env also critically influences its relatively low and pH-dependent fusion activity. Furthermore, the poor infectivity of ENTV pseudovirions in human cells was significantly improved by either replacing the SU subunit of ENTV Env with that of JSRV Env Phenylethanolamine N-methyltransferase or overexpressing the functional Hyal2 receptor in target cells, suggesting that ENTV SU-Hyal2 interaction is likely to be the limiting step for viral infectivity. Collectively, our data reveal that the fusogenicity of ENTV Env is intrinsically lower than that of JSRV Env and that ENTV requires a more acidic pH for fusion, which may occur in an intracellular compartment(s) distinct from that used by JSRV.”
“Eastern equine encephalitis virus ( EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon.

Viral genetic diversity was positively correlated with host immunity, represented by levels of alanine aminotransferase (ALT), but was negatively correlated with the viral copy number. During the immunotolerant phase, when the host immunity was feeble (ALT < 20 U/liter), viral nucleotide diversity decreased while copy LY2109761 cost numbers increased. Rates of evolutionary change derived

for different patients were in a very narrow range (1.6 x 10(-5) to 5.4 x 10(-5)/site/year). As the disease progressed toward the immunoclearance phase (ALT > 20 U/liter), viral diversity increased but copy numbers decreased. Evolutionary rates varied among patients in accordance with their levels of ALT, ranging from 9.6 x 10(-6) to 3.2 x 10(-4)/site/year. More than half (19/32 sites) of positively selected sites resided in immune epitopes, suggesting their possible role in host immunity. Our results demonstrate that host immunity is a dominant factor in HBV evolution. Different selective forces, including immune-mediated positive selection and virus-mediated negative selection, operate in tandem in shaping viral population dynamics within a host.”
“Presynaptic CB, cannabinoid receptors are frequently targets of endogenous cannabinoids (endocannabinoids) released from

postsynaptic neurons. It is known that the glutamatergic Akt inhibitor afferent input to a neuron can trigger endocannabinoid production and that the released endocannabinoid can suppress the glutamatergic input. We tested the hypothesis that activation of the glutamatergic input to a neuron leads to an endocannabinoid-mediated suppression of the GABAergic afferent input to the same neuron. Spontaneous postsynaptic currents (sPSCs) were recorded with patch-clamp techniques in Purkinje cells

Atezolizumab manufacturer in mouse cerebellar brain slices. Activation of the climbing fiber-mediated glutamatergic input to Purkinje cells led to a suppression of the sPSCs by 34 +/- 3%. This suppression was mostly due to suppression of GABAergic spontaneous inhibitory postsynaptic current (sIPSCs), because 93% of the sPSCs recorded in Purkinje cells were GABAergic sIPSCs. Blockade of ionotropic, but not metabotropic glutamate receptors, prevented the suppression. The climbing fiber activation led to an increase in calcium concentration in the Purkinje cells, and this increase was necessary for the suppression of sPSCs, because the suppression did not occur when the calcium increase was prevented by BAPTA. No sPSC suppression was observed in the presence of the CB, antagonist rimonabant or the diacylglycerol lipase inhibitor orlistat. In a further series of experiments GABAergic sIPSCs were recorded: these sIPSCs were also suppressed after climbing fiber activation, and the suppression was sensitive to the CB, antagonist SLV319.

We conducted a randomised, double-blind, crossover study in 14 healthy volunteers to determine the effects of oral inorganic nitrate (8 mmol KNO3) vs. placebo (8 mmol KCl) on endothelial function, measured by flow-mediated dilatation (FMD) of the brachial artery, prior to and 3 h following capsule ingestion. In addition, blood pressure (BP) was measured and aortic pulse wave velocity (aPWV) determined. Finally, blood, saliva and urine samples

were collected for chemiluminescence analysis of [nitrite] and [nitrate] prior to and 3 h following interventions. Inorganic nitrate supplementation had no effect on endothelial function in healthy volunteers (6.9 +/- 1.1% pre- to 7.1 +/- 1.1% post-KNO3).

Despite this, there was a significant elevation of plasma [nitrite] (0.4 +/- 0.1 mu M pre- to 0.7 +/- buy AZD3965 0.2 mu M post-KNO3, p < 0.001). In addition these changes in [nitrite] were associated with a decrease in systolic BP (116.9 +/- 3.8 mm Hg pre- vs. 112.1 +/- 3.4 mm Hg post-KNO3, p < 0.05) buy Trichostatin A and aPWV (6.5 +/- 0.1 m/s pre- to 6.2 +/- 0.1 post-KNO3, p < 0.01). In contrast KCl capsules had no effect on any of the parameters measured. These findings demonstrate that although inorganic nitrate ingestion does not alter endothelial function per se, it does appear to improve blood flow, in combination with a reduction in blood pressure. It is likely that these changes are due to the intra-vascular production of NO. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.”
“Microbial fuel cells (MFCs) represent an emerging technology for electricity generation from renewable biomass. Given the demand for a better understanding of the bio/inorganic interface

that plays a key role in MFC energy production, small-scale MFCs are receiving considerable attention owing to their intrinsic advantages in both fundamental studies Dolutegravir chemical structure and applications as high-throughput platforms. Here, we present a brief review centered on the development of miniature MFCs at the milliliter to microliter scale. The principles, design motifs and experimental demonstrations of representative miniature MFC devices and systems are introduced, followed by a discussion of the key challenges and opportunities for realizing the exciting potentials of miniaturized MFCs.”
“Proteomics is routinely utilized for biomarker discovery above and beyond its general use in basic science. Multiple platforms provide a robust pipeline of candidates that require verification and validation as biomarkers of disease. Within the field of oncology, tissue biomarkers are in high demand as tools of diagnosis, prognosis and prediction of response to therapy. By examining the proteome, rather than the transcriptome, there is the potential to directly interrogate the drug targets and define biomarkers at the most proximate level.

Extracorporeal membrane oxygenation implantation was performed through the femoral vessels or axillary artery or through the right atrium and ascending aorta. Additional intra-aortic balloon pumps were used in 30 patients.

Results: Average patient age was 60.1 +/- 13.6 years. There were 35 male patients. Average duration of extracorporeal membrane oxygenation was 6.4 +/- 4.5 days. Twenty-five patients could be successfully weaned from extracorporeal MI-503 in vivo membrane oxygenation.

The 30-day mortality was 53% (24/ 45 patients). The in-hospital mortality was 71% (32/ 45 patients). Thirteen (29%) patients could be successfully discharged. After a follow-up period of up to 3 years, 10 (22%) patients were still alive.

Conclusions: Extracorporeal membrane oxygenation offers sufficient cardiopulmonary support in adults with similar hospital and midterm survival rates to those of other mechanical support systems. Early indication, alternative peripheral cannulation techniques, and reduced anticoagulation to avoid perioperative bleeding could improve our results with increasing

GDC-0449 mouse experience.”
“The serotonin 5-HT6 receptor has become a promising target for the treatment of neuropsychological diseases, such as affective disorders. Increasing evidence implicates stress and its effector system, the hypothalamic-pituitary-adrenal Fluocinolone acetonide (HPA) axis, in the neurobiology of depression. In addition, there are important memory disturbances in stress-related psychiatric disorders that have been associated to an impairment of the HPA axis reactivity. The aim of the present work is to study the functional interactions between 5-HT6 receptors and HPA axis. In

a situation of increased HPA axis responsiveness (maternal separation, MS) no differences were found in the expression of 5-HT6 gene in the hippocampus or frontal cortex, although serotonin levels were higher in the frontal cortex of MS rats. 5-HT6 receptor mRNA expression increased significantly in the hippocampus in a situation of decreased glucocorticoid levels, such as adrenalectomy. Cognitive deficits associated to HPA dysfunction, such those found in the MS model, were fully reversed by administration of SB271046, a selective 5-HT6 receptor antagonist. A chronic treatment with SB271046 did not modify CRF mRNA levels in the hypothalamus, but there was a higher glucocorticoid receptor density in the hippocampus compared to control. In contrast, in the frontal cortex, treatment with SB271046 induced a significant decrease in glucocorticoid receptor density.