Copyright (C) 2010 S Karger AG, Basel”
“We tested the hypot

Copyright (C) 2010 S. Karger AG, Basel”
“We tested the hypothesis that oxidized low-density lipoprotein (oxLDL)-induced click here inactivation of Akt within endothelial progenitor cells (EPCs) is mediated at the level of Phosphoinositide 3-kinase (PI3K), specifically by nitrosylation of the p85 subunit of PI3K, and that this action is critical in provoking oxLDL-induced EPC apoptosis. Hypercholesterolemic ApoE null mice had a significant reduction of the phosphorylated Akt (p-Akt)/Akt ratio in EPCs, as

well as a greater percentage of apoptosis in these cells than EPCs isolated from wild-type (WT) C57Bl/6 mice. EPCs were isolated from WT spleen and exposed to oxLDL in vitro. oxLDL increased O(2)(-) and Selleckchem BVD-523 H(2)O(2) in these cells and induced a dose-and time-dependent reduction in the p-Akt/Akt ratio and increase in EPC apoptosis. These effects were significantly reduced by the antioxidants superoxide dismutase, L-NAME, epicatechin and FeTPPs. oxLDL also induced nitrosylation of the p85 subunit of PI3K and subsequent dissociation of the p85 and p110 subunits, an effect significantly reduced by all the antioxidant agents tested. EPC transfection with a constitutively active Akt isoform (Ad-myrAkt)

significantly reduced oxLDL-induced apoptosis of WT EPCs. The present findings indicate that oxLDL disrupts the PI3K/Akt signaling pathway at the level of p85 in EPCs. This dysfunction can be reversed by ex vivo antioxidant therapy. Copyright (C) 2010 S. Karger AG, Basel”
“Background/Aims: Aminopeptidase P (APP) is specifically enriched in caveolae on the luminal surface of pulmonary vascular endothelium. APP antibodies bind lung endothelium in vivo and are rapidly and actively pumped across the endothelium into lung tissue. Here we characterize the immunotargeting properties and pharmacokinetics of the APP-specific recombinant antibody 833c. Methods: We used in situ binding, biodistribution analysis and in vivo imaging to assess the lung targeting of 833c. Results: HSP90 More

than 80% of 833c bound during the first pass through isolated perfused lungs. Dynamic SPECT acquisition showed that 833c rapidly and specifically targeted the lungs in vivo, reaching maximum levels within 2 min after intravenous injection. CT-SPECT imaging revealed specific targeting of 833c to the thoracic cavity and co-localization with a lung perfusion marker, Tc99m-labeled macroaggregated albumin. Biodistribution analysis confirmed lung-specific uptake of 833c which declined by first-order kinetics (t(1/2) = 110 h) with significant levels of 833c still present 30 days after injection. Conclusion: These data show that APP expressed in endothelial caveolae appears to be readily accessible to circulating antibody rather specifically in lung.

We report the good long-term outcome of endovascular

We report the good long-term outcome of endovascular repair of a large innominate artery true aneurysm due to Takayasu’s arteritis. A stent graft was safely and successfully deployed to exclude the aneurysm; assessment by vascular imaging at 8-year follow-up demonstrated

the efficacy of the procedure. (J Vasc Surg 2012;56:504-7.)”
“The invaluable antineoplastic bisindole alkaloids of Catharanthus roseus and their precursor, vindoline, are not produced in cell cultures. The intricacies involved in endogenous (cellular differentiation) and exogenous (elicitation) regulation of their biosynthesis need to be dissected out for favorable exploitation. This study aimed at elucidating the effect of Pythium aphanidermatum homogenate and methyl jasmonate (MeJa) on in vitro cultures (of cv. ‘Dhawal’) representing increasing level of differentiation (suspension < callus < shoots) in terms of alkaloid accumulation and transcript abundance of strictosidine beta-d-glucosidase (SGD) and acetyl-CoA: 4-O-deacetylvindoline 4-O-acetyl-transferase (DAT) genes, representing intermediate and late steps, respectively, of terpenoid indole alkaloid biosynthesis. Elicitation of suspension

cultures caused transcriptional upregulation of SGD and enhanced the accumulation of total alkaloids but did not produce vindoline as DAT transcripts were always found to be absent in suspension-cultured cells. Vindoline was also not detected in unelicited and MeJa-treated callus but appeared upon elicitation with fungal homogenate for 24 h that coincided see more with maximal DAT transcription. Transcript levels of both genes increased upon elicitation of callus but remained below

levels present in the mature plant leaf. Elicitation caused appearance of vindoline in shoots and increased the transcript abundance of both genes beyond levels observed in the mature plant leaf. Differentiation was essential Flavopiridol (Alvocidib) for expression of DAT but not SGD, and vindoline biosynthetic potential increased with it.”
“Objective: This was a systematic review and meta-analysis of the mode of anesthesia and outcome after endovascular aneurysm repair (EVAR).

Methods: Review methods were according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Published and unpublished literature was searched. The primary outcome was 30-day mortality. Secondary outcomes were categorized for patient selection, perioperative outcomes, and postoperative outcomes. Weighted mean differences (WMD) were calculated for continuous variables, such as length of stay, and pooled odds ratios (OR) were calculated for discrete variables such as major morbidity.

Results: Ten studies of 13,459 patients given local anesthesia (LA) or general anesthesia (GA) were eligible for analysis. There was no difference in 30-day mortality. The LA patients were older than the GA patients (WMD, 0.17; P = .

Es32 was more sensitive than Es524, with toxicity detected at 50

Es32 was more sensitive than Es524, with toxicity detected at 50 mu g/L Cu, whereas Es524 displayed negative effects only when exposed to 250 mu g/L Cu. Differential soluble proteome profiling for each strain exposed to sub-lethal copper levels allowed to identify the induction of proteins related to processes such as energy production, selleck chemical glutathione metabolism as well as accumulation of HSPs. In addition, the inter-strain comparison of stress-related proteomes led to identify features related to copper tolerance in Es524, such as striking expression of a PSII Mn-stabilizing protein and a Fucoxanthine chlorophyll a c binding protein.

Es524 also expressed specific stress-related enzymes such as RNA helicases from the DEAD box families and a vanadium-dependent bromoperoxidase. These observations were supported by RT-qPCR for some of the identified genes and an enzyme activity assay for vanadium-dependent bromoperoxidase. Therefore,

the occurrence of two different phenotypes within two distinct E. siliculosus strains studied at the physiological and proteomic levels strongly suggest that persistent 7-Cl-O-Nec1 cell line copper stress may represent a selective force leading to the development of strains genetically adapted to copper contaminated sites.”
“Objective: Current information regarding coverage of accessory renal arteries (ARAs) during endovascular aneurysm repair (EVAR) is based on small case series with limited follow-up. This study evaluates the outcomes of ARA coverage in a large contemporary cohort.

Methods: Consecutive EVAR data from January 2004 to August 2010 were collected in a prospective database at a University Hospital. Patient and aneurysm-related characteristics, imaging studies, and ARA coverage versus preservation were analyzed. Volumetric analysis of three-dimensional reconstruction computed tomography scans was used to assess renal infarction volume extent. Long-term renal function and overall

technical success of aneurysm exclusion were compared.

Results: A cohort of 426 EVARs was identified. ARAs were present in 69 patients with a mean follow-up of 27 months (range, 1 to 60 months). Forty-five ARAs were covered in 40 patients; 29 patients had intentional ARA preservation. Patient and anatomic characteristics were similar between groups except Beta adrenergic receptor kinase that ARA coverage patients had shorter aneurysm necks (P = .03). Renal infarctions occurred in 84% of kidneys with covered ARAs. There was no significant deterioration in long-term glomerular filtration rate when compared with patients in the control group. No difference in the rate of endoleak, secondary procedures, or the requirement for antihypertensive medications was found.

Conclusions: This study is the largest to date with the longest follow-up relating to ARA coverage. Contrary to previous reports, renal infarction after ARA coverage is common. Nevertheless, coverage is well tolerated based upon preservation of renal function without additional morbidity.

A scoring system based on anatomic criteria has been developed to

A scoring system based on anatomic criteria has been developed to facilitate patient selection

for CAS. Advancements in simulation science also enable IWP-2 solubility dmso case evaluation through patient-specific virtual reality (VR) rehearsal on an endovascular simulator. This study aimed to validate the anatomic scoring system for CAS using the patient-specific VR technology.

Methods: Three patients were selected and graded according to the CAS scoring system (maximum score, 9): one easy (score, <4.9), one intermediate (score, 5.0-5.9), and one difficult (score, >7.0). The three cases were performed on the simulator in random order by 20 novice interventionalists pretrained in CAS. Technical performances were assessed using simulator-based metrics and expert-based ratings.

Results: The interventionalists took significantly longer to perform the difficult CAS case (median, 31.6 vs 19.7 vs 14.6 minutes; P < .0001) compared with the intermediate and easy cases; similarly, more fluoroscopy time (20.7 vs 12.1 vs 8.2 minutes; P <. 0001), contrast volume (56.5 vs 51.5 vs 50.0 mL; P = .0060), and roadmaps (10 vs 9 vs mTOR inhibitor 9; P = .0040) were used. The quality of performance declined significantly as the cases became more

challenging (score, 24 vs 22 vs 19; P < .0001).

Conclusions: The anatomic scoring system for CAS can predict the difficulty of a CAS procedure as measured by patient-specific VR. This scoring system, with or

without the additional use of patient-specific VR, can guide Docetaxel chemical structure novice interventionalists in selecting appropriate patients for CAS. This may reduce the perioperative stroke risk and enhance patient safety. (J Vasc Surg 2012;56:1763-70.)”
“The intrinsically unfolded protein a-synuclein has an N-terminal domain with seven imperfect KTKEGV sequence repeats and a C-terminal domain with a large proportion of acidic residues. We characterized pK(a) values for all 26 sites in the protein that ionize below pH 7 using 2D H-1-N-15 HSQC and 3D C(CO)NH NMR experiments. The N-terminal domain shows systematically lowered pK(a) values, suggesting weak electrostatic interactions between acidic and basic residues in the KTKEGV repeats. By contrast, the C-terminal domain shows elevated pKa values due to electrostatic repulsion between like charges. The effects are smaller but persist at physiological salt concentrations. For alpha-synuclein in the membrane-like environment of sodium dodecylsulfate (SDS) micelles, we characterized the pK(a) of His50, a residue of particular interest since it is flanked within one turn of the a-helix structure by the Parkinson’s disease-linked mutants E46K and A53T. The pK(a) of His50 is raised by 1.4 pH units in the micelle-bound state.

This paper describes a species-specific, real time polymerase cha

This paper describes a species-specific, real time polymerase chain reaction (PCR), based on unique molecular markers that were found in the G-protein-coupled chemokine receptor (GPCR) gene sequences of CaPVs, that uses dual hybridization probes for their simultaneous detection, quantitation and genotyping.


assay can differentiate between CaPV strains based on differences in the melting point temperature (Tm) obtained after fluorescence melting curve analysis (FMCA). It is highly sensitive and presents low intra- and inter-run variation.

This real time PCR assay will make a significant contribution to CaPV diagnosis and to the better understanding of the epidemiology of CaPVs by

enabling rapid genotyping and gene-based PD-0332991 chemical structure classification this website of viral strains and unequivocal identification of isolates. (C) 2010 Elsevier B.V. All rights reserved.”
“Steroid 11 beta-hydroxylase (CYP11B1; EC is a mitochondrial enzyme located in the zona fasciculata of the adrenal cortex and also in the brain that mediates the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone (DOC) to corticosterone. Inhibitors of CYP11B1, such as metyrapone and etomidate, reduce glucocorticoid synthesis and raise levels of DOC providing greater availability for metabolic conversion to the GABA(A) receptor modulating neurosteroid allotetrahydrodeoxycorticosterone (THDOC). Because THDOC is a potent anticonvulsant, it is plausible that CYP11B1 inhibitors could protect against seizures. Here we demonstrate that metyrapone affords dose-dependent Adenosine protection against 6-Hz seizures 30 min after injection (ED50, 191 mg/kg), but is markedly more potent at 6 h (ED50, 30 mg/kg). Similarly, etomidate is also protective at 30 min and 6 h (ED50 values,

4.5 and 1.7 mg/kg). Finasteride, an inhibitor of neurosteroid synthesis, attenuated the anticonvulsant effects of both CYP11B1 inhibitors at 6 h, but not 30 min following their injection. Plasma THDOC levels measured by liquid chromatography-mass spectrometry were markedly increased 6 h after injection of both CYP11B1 inhibitors and this increase was attenuated by finasteride pretreatment. We conclude that inhibition of CYP11B1 causes delayed seizure protection due to slow build-up of neurosteroids. Early seizure protection is independent of neurosteroids. Published by Elsevier Ltd.”
“The gene encoding the capsid protein in ORF1 of the genome of infectious myonecrosis virus (IMNV) (Gen-Bank AY570982) was amplified into three parts named CP-N (nucleotides 2248-3045), CP-I (nucleotides 3046-3954) and CP-C (nucleotides 3955-4953).

“Psychiatric neurosurgery, specifically stereotactic ablat

“Psychiatric neurosurgery, specifically stereotactic ablation, has continued since the 1940s, mainly at a few centers in Europe and the US. Since the late 1990s, the resurgence of interest in this field has been remarkable; reports of both lesion procedures and the newer technique of deep brain stimulation (DBS) have increased rapidly. In early 2009, the US FDA granted limited humanitarian approval for DBS for otherwise intractable obsessive-compulsive disorder (OCD), the first SAHA ic50 such approval for a psychiatric illness. Several factors explain the emergence

of DBS and continued small-scale use of refined lesion procedures. DBS and stereotactic ablation have been successful and widely used for movement disorders. There remains an unmet clinical need: current drug and behavioral treatments offer limited benefit to some seriously ill people. Understandings of the neurocircuitry underlying psychopathology and the response to treatment, while still works in progress,

are much enhanced. Here, we review Sapanisertib mouse modern lesion procedures and DBS for OCD in the context of neurocircuitry. A key issue is that clinical benefit can be obtained after surgeries targeting different brain structures. This fits well with anatomical models, in which circuits connecting orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), basal ganglia, and thalamus are central to OCD pathophysiology and treatment response. As in movement disorders, dedicated interdisciplinary teams, here led by psychiatrists, are required to implement these procedures and maintain care for patients so treated. Available data, although limited, support the promise of stereotactic ablation or DBS in carefully selected patients. Benefit in such cases appears not to be confined to obsessions and

compulsions, but includes changes in affective state. Caution is imperative, and key issues in long-term management of psychiatric neurosurgery patients deserve focused attention. DBS and contemporary ablation also present different patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use. Neuropsychopharmacology Reviews (2010) 35, 317-336; doi:10.1038/npp.2009.128; published online Protirelin 16 September 2009″
“Objective: Percutaneous pulmonary valve replacement has been recently introduced into clinical practice. Patients with transcatheter pulmonary valve replacement will definitely face the problems of valve degeneration. In addition to surgical re-replacement of the degenerated bioprosthetic valves, we studied the replacement of degenerated bioprosthetic valves with transcatheter reimplantation of stent-mounted pulmonary valves.

Methods: Percutaneous pulmonary valve replacement was first performed in 6 sheep used a homemade valved stent.

The MsrA(-/-) mice did not have any significant difference in spo

The MsrA(-/-) mice did not have any significant difference in spontaneous distance traveled when compared to controls at 17 months of age. in contrast, our previous report showed decreased locomotor activity in the MsrA(-/-) mice at 12 months of age and older when fed ad-libitum. After completion of the caloric restriction diet, dopamine levels were comparable to control mice. This differs from the abnormal dopamine levels previously

observed in MsrA(-/-) mice fed ad-libitum. Thus, caloric restriction had a neutralization effect on MsrA ablation. In summary, it is suggested that caloric restriction alleviates abnormal locomotor activity and dopamine levels in the brain of the methionine sulfoxide reductase A knockout mouse. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: We investigated the long-term HKI-272 purchase outcome of urethral reconstruction using colonic mucosa grafts for long segment, complex urethral strictures. Another aim was to identify clinical factors impacting long-term outcomes.

Materials and Methods: We retrospectively reviewed the records of 36 consecutive patients with a mean age of 39.8 years (range 17 to 70) who underwent colonic mucosal graft urethroplasty for long segment, complex urethral stricture from October 2000 to November 2006. Patients were evaluated postoperatively at scheduled office visits at our institution and/or by telephone interview. Successful repair

was defined as normal voiding without any postoperative procedure such as dilation.

Results: Urethral reconstruction with done with colonic mucosa grafts 10 to 20 cm long (mean 15.1). One patient was lost to followup. Carteolol HCl Mean followup in the remaining cases was 53.6 months (range 26 to 94). Outcomes were successful in 30 of 35 patients (85.7%). Complications, specifically meatal stenosis, bulbar or bulbomembranous urethral stenosis and proximal anastomotic site stricture, developed in 5 patients (13.3%).

Conclusions: Colonic mucosa graft urethroplasty is a feasible procedure for complex urethral strictures. The most common complications are meatal stenosis and stenosis at the anastomosis.”

of cortical representational maps and their plasticity have been described in dystonia. A common polymorphism for BDNF has been associated with abnormal cortical plasticity, and thus might contribute to pathogenesis of dystonia in some subjects. As a first step towards this suggestion, the current study examined the prevalence of this polymorphism. BDNF genotype was examined in 34 subjects with cervical dystonia, 54 age-matched healthy controls, and 53 subjects with a different movement disorder, Parkinson’s disease. ApoE genotype, known to influence neurological outcome in some conditions, was also examined as a control. In subjects with cervical dystonia, the val(66)met polymorphism was approximately twice as prevalent when compared to either control group.

Methods/Results: Using in vivo stationary microperfusion, we obse

Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO(3)(-) reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH4Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases Gemcitabine proximal tubule Na+ reabsorption.

The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension. Copyright (C) 2012 S. Karger AG, Basel”
“Both schizophrenia and oxidative stress have been associated with immune system abnormalities in interleukin-2 and -6 (IL-2; IL-6) and increases Chk inhibitor in superoxide dismutase (SOD) activity. These abnormalities may improve during antipsychotic drug treatment that reduces symptoms in schizophrenic patients.

Subjects included 30 healthy controls

(HC) and 78 schizophrenic (SCH) in-patients who were randomly assigned to 12 weeks of double-blind treatment with risperidone 6 mg/day or haloperidol 20 mg/day. Ratings using the Positive and Negative Syndrome Scale (PANSS) were correlated with blood SOD and serum IL-2 levels.

SCH patients who were medication-free for 2 weeks had greater SOD, IL-2, and IL-6 levels than HC. At baseline, these SOD elevations were associated Flucloronide with higher PANSS total scores and the IL-2 elevations with lower PANSS positive symptom scores. The SOD and IL-2 levels in the SCH were also positively correlated. After treatment, PANSS positive symptoms and both SOD and IL-2 showed

a significant decrease, but IL-6 showed no change. The SOD and IL-2 reductions were correlated with the reductions in PANSS total score, and SOD reductions also correlated with positive subscore reductions. Females showed these associations more strongly than males.

Our results suggest that the dysregulation in the cytokine system and oxidative stress in patients with schizophrenia is implicated in clinical symptoms and is improved at least partially with antipsychotic treatment. The stronger associations in females deserve further study and confirmation.”
“Over recent decades biotechnology has made significant advances owing to the emergence of powerful biochemical and biophysical instrumentation. The development of such technologies has enabled high-throughput assessment of compounds, the implementation of recombinant DNA technology, and large-scale manufacture of monoclonal antibodies.

Different loci are associated with varenicline vs bupropion respo

Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to selleck chemical guide treatment decisions. Neuropsychopharmacology (2012) 37, 641-650; doi: 10.1038/npp.2011.232;

published online 2 November 2011″
“Intravenous immunoglobulin (IVIg) is therapeutically used in a variety of immune-mediated diseases. The beneficial effects of Wig in auto-antibody-mediated diseases can be explained by neutralization, accelerated clearance and prevention of Fc gamma-receptor binding of auto-antibodies. However, the means by which Wig exerts therapeutic effects in disorders mediated by cellular immunity have remained enigmatic. Clinical improvements, followed by IVIg treatment, often extend beyond the half-life of infused IgG, thereby indicating that IVIg modifies the cellular immune compartment for a

prolonged period. Here, we discuss recent advances in the MM-102 molecular weight understanding of different, mutually non-exclusive mechanisms of action of Wig on cells of the innate and adaptive immune system. These mechanisms might explain the beneficial effects of IVIg in certain autoimmune and inflammatory diseases.”
“Whipple’s disease (WD) is a chronic multisystemic infection, caused by the bacterium Tropheryma whipplei. The main clinical presentations are classic WD (CWD) with histologic lesions in the gastrointestinal tract, endocarditis, and isolated. neurologic infection. The current strategy for diagnosis remains invasive.The present study aimed to select the protein candidates for serological diagnosis of WD. The first step was to identify candidate proteins by an immunoproteomic approach combining 2-DE using a total extract of a T. whipplei, irrununoblotting, and

MS. The second step was to validate the discovered biornarkers using a recombinant protein-based ELISA. Serum samples from 18 patients with WD and from 54 control individuals were tested. A sugar ABC transporter, TWT328 (sensitivity (Se) 61%, specificity (Sp) 87%, positive predictive value (PPV) 61%, negative predictive value (NPV) 87%, and Dichloromethane dehalogenase positive likelihood ratio (PLR) 4.69) was the best marker for development of serodiagnosis for CWD. We also obtained a reproducible immunoreactive protein pattern for patients with isolated neurological infection due to T whipplei (Se 100%, Sp 93%, PPV 55.5%, NPV 100%, and PLR 13.51) as an encouraging step towards noninvasive diagnosis of this particular manifestation. Nine recombinant candidates have been successfully screened with serum samples. Results from these ELISA assays skewed with those obtained with immunoblots.”
“Impulsive action, the failure to withhold an inappropriate response, is treated clinically with dopamine agonists such as amphetamine.

Male Wistar rats were implanted with guide cannulae

to pe

Male Wistar rats were implanted with guide cannulae

to perform bilateral microinjections into the PFC and microdialysis experiments in the amygdala and/or ventral hippocampus, simultaneously. Spontaneous motor activity was monitored in the open field.

Injections of CPP (1 mu g/0.5 mu l) into the PFC increased dialysate concentrations of dopamine and acetylcholine in the amygdala, acetylcholine and free corticosterone in the hippocampus and MS-275 in vitro also motor activity. Simultaneous injections of muscimol (0.5 mu g/0.5 mu l) into the PFC counteracted the increases of dopamine and acetylcholine in the amygdala and hippocampus and also significantly reduced the peak increase of corticosterone in the hippocampus. Injections of muscimol (0.05 and 0.5 mu g/0.5 mu l) reduced the NF-��B inhibitor increases of motor activity produced by prefrontal NMDA antagonists.

These results suggest that the hypofunction of NMDA receptors in the PFC produces corticolimbic hyperactivity through the activation

of prefrontal efferent projections to subcortical/limbic areas.”
“Simian hemorrhagic fever virus (SHFV) is an arterivirus that causes severe disease in captive macaques. We describe two new SHFV variants subclinically infecting wild African red-tailed guenons (Cercopithecus ascanius). Both variants are highly divergent from the prototype virus and variants infecting sympatric red colobus (Procolobus rufomitratus). All known SHFV variants are monophyletic and share three open reading frames not present in other arteriviruses. Our data suggest a need to modify the current arterivirus classification.”
“Performance on the Cambridge Neuropsychological Test Automated Battery touchscreen paired-associates learning (PAL) test is predictive of Alzheimer’s disease and impaired in schizophrenia and chronic drug users. An automated computer touchscreen PAL task for rats has been previously GNAT2 established. A pharmacologically validated PAL task for mice would be a highly valuable tool, which could be useful for a number of experimental aims including drug discovery.

This study sought to investigate the effects of systemic administration of cholinergic

agents on task performance in C57Bl/6 mice.

Scopolamine hydrobromide (0.02, 0.2, and 2.0 mg/kg), dicyclomine hydrochloride (M(1) receptor antagonist; 2.0, 4.0, and 8.0 mg/kg), and donepezil hydrochloride (cholinesterase inhibitor; 0.03, 0.1, and 0.3 mg/kg) were administered post-acquisition in C57Bl/6 mice performing the PAL task.

Scopolamine (0.2 and 2.0 mg/kg) and dicyclomine (at all administered doses) significantly impaired PAL performance. A significant facilitation in PAL was revealed in mice following donepezil administration (0.3 mg/kg).

The present study shows that mice can acquire the rodent PAL task and that the cholinergic system is important for PAL task performance. M(1) receptors in particular are likely implicated in normal performance of PAL.