0 software (Tamura

et al., 2007). The origin of the reference strains and their GenBank accession numbers are as follows: Fukui, Japan –AB090073, AB090082, AF202972; Okinawa, Japan –AB190940–AB190942, AB190944, AB190948, AB190950, AB190951, AB190956, AB246733-AB246735; Vietnam –FJ798952, FJ798953, FJ798955, FJ798956, FJ798960, FJ798962, FJ798967–FJ798969; Thailand –GU173873–GU173879; China –AF247651, AF249275, AF367250, EU681369; Australia –AF202973, AF282853; Sweden –AY330664; selleckchem UK –AE000511; and United States –AB015414–AB015415. For the aligned cagA gene sequences, genetic distances were estimated using the Kimura 2-parameter method (Kimura, 1980), and for the translated full amino acid sequences of the CagA protein, the JTT (Jones–Taylor–Thornton) matrix-based method (Jones et al., 1992) was used. Phylogenetic trees were constructed using the neighbor-joining TSA HDAC molecular weight method (Saitou & Nei, 1987), and a bootstrap test (1000 replicates) for phylogeny was performed also using mega 4.0 (Tamura et al., 2007). It has been demonstrated previously that CagA can be divided into Western and East Asian types by the kind of amino acid at a tyrosine phosphorylation site (Higashi et

al., 2002a). Strains that possess WSS (Western CagA-specific, SHP-2-binding sequence) are classified as Western type CagA, whereas strains that possess ESS (East either Asian CagA-specific, SHP-2-binding sequence) are classified as East Asian type CagA (Higashi et al., 2002a). Tyrosine phosphorylation of CagA occurs at unique Glu–Pro–Ile–Try–Ala (EPIYA) motifs repeated several times in the C-terminal region. These

EPIYA motifs are involved in the interaction of CagA with SHP-2. The first and second EPIYA motifs (designated as ‘EPIYA-A’ and ‘EPIYA-B’, respectively) are present in almost all Western and East Asian CagA proteins, although the subsequent amino acid sequence is quite different between Western and East Asian type CagA. The third EPIYA motifs included in WSS or ESS were designated as ‘EPIYA-C’ or ‘EPIYA-D’ (Higashi et al., 2002a), respectively. A total of 19 H. pylori strains from 19 patients was used in this study: eight patients with gastritis, three patients with duodenal ulcer, six with gastric ulcer, and two with gastric cancer. There were ten males and nine females, with a mean age of 52.89±11.55 years (range from 30 to 67 years). All Philippine strains examined were cagA-positive and the CagA genotypes of the 19 Philippine strains are shown in Table 2. The Philippine strains can be divided into East Asian (five strains) or Western (14 strains) types. Sequencing of the cagA gene showed a variable size of 3504–3651 bp full-length encoding region, and the predicted size of CagA in 19 strains ranged from 1168 to 1217 amino acids.

The images include a wealth of macroscopic images, light

microscopy images depicting numerous staining methods and electron microscopy images. Where applicable there are useful tables and schematic drawings for easier understanding and recall. Last but not least the index is very detailed and comprehensive making a search for the basic definitions or findings for a topic of interest speedy and rewarding. The preface states that the general intention of this edition, similar to the previous editions, is to provide a concise introductory text covering the basic morphology of lesions underlying diseases of the nervous system, limiting pathophysiological considerations to essential principles and purposefully excluding historical, clinical, neurological,

radiological imaging data and reference listings. In my see more opinion, this is exactly what the book provides. Although the information provided in the book is a concise and ‘basic’ introduction to the various diseases of the nervous system and their underlying pathology; this edition, similar to previous editions, will surprise the reader with how much valuable information, covering nearly whole spectrum of neuropathological processes, can be included in just over 400 pages. There is no online p38 MAPK assay access or accompanying CD-ROM for image download. However, in my opinion this is an insignificant downside for a practical diagnostic manual providing up to date information on

a broad range of nervous system and skeletal muscle pathologies for a price of £65.00. As a concise easily readable introductory text, with numerous high quality illustrations supplemented with short clear figure legends, this book is a ‘must-have’ for anyone wishing to learn or revise the basics of neuropathology; be they a student, trainee, experienced specialist or scientist. The spectrum of readers who would find the book of value is broad. In addition to pathologists it would provide an excellent introduction Dichloromethane dehalogenase to neuropathology for those in clinical specialties, such as neurology, neurosurgery, psychiatry, neuroradiology, neuroendocrinology and neuroscience. In view of the valuable updates, I am very glad to add this new edition on the bookshelf right next to my old well-loved, hence very much worn-out blue book. I would recommend you to do the same! “
“This chapter contains sections titled: Introduction Modeling Specific Functions or Behaviors Experimental Manipulations: Consequences of Drugs, Toxicants, and Lesions Relevance to Humans References “
“It is an honour to be appointed as the new Editor-in-Chief of Neuropathology and Applied Neurobiology and I look forward to the challenge of following in the footsteps of five distinguished editors to lead the journal forward in the coming years.

24 The persistent myocardial necrosis that leads to an elevated troponin in patients on dialysis has been attributed to left ventricular hypertrophy61 or coronary artery atherosclerosis.2 However, studies www.selleckchem.com/products/Romidepsin-FK228.html using cardiac magnetic resonance imaging have demonstrated that troponin may be high without evidence of myocardial infarction, suggesting that pathologies such as microcirculatory disturbances or increased sympathetic tone may explain the increase in troponin.62 Although there is strong evidence that elevated troponin confers a poorer prognosis in an asymptomatic patient undergoing dialysis,

there is currently no evidence to support biomarker-guided therapy for the individual patient. The most practical reason for measuring troponin in this context is to determine a ‘baseline’ level for each patient that can be referred to if the patient subsequently presents with cardiac symptoms. Whether cTnT or cTnI is measured in this context is not as important as that the same assay be used subsequently. As a tool for identifying patients

at risk, cTnT may be superior to cTnI because the evidence is more robust and interpretable for this assay, largely because of better standardization of assays than cTnI, and selleck screening library because measuring cTnT with current assays will identify more patients at risk. However, elevated cTnI had a stronger mortality association than cTnT in one large study, although this may be due to the chosen cut-off for cTnI being higher than that used for cTnT because of different assay characteristics.43 The performance of troponin assays continues to improve and ‘high-sensitivity’ assays are being developed

that may make the proportion of patients receiving dialysis with elevated cTnI more similar to that with elevated cTnT.22 Regardless of the differences between assays or why the troponin was measured, an abnormal troponin level should underscore the need to carefully review the patient, who is at least twice as likely to die as the patient without elevated troponin. Elevated levels of BNP are also Vildagliptin associated with poorer survival in patients undergoing both haemodialysis43,47,48 and peritoneal dialysis.44,63 The association of NT-BNP-76 with mortality was independent of left ventricular ejection fraction in one study44 and both NT-BNP-76 and extracellular fluid volume overload were independent predictors of cardiovascular mortality in another.64 Patients whose NT-BNP-76 increased at 90 days in the highest tertile of change (≥429 ng/L) had a more than twofold risk of death compared with patients experiencing the lowest tertile of change.47 Although most studies measured NT-BNP-76, higher levels of BNP-32 are also associated with mortality.5 Potential causes of elevated BNP levels in patients undergoing dialysis include systolic dysfunction,5 diastolic dysfunction,65 increased left ventricular mass49 and coronary artery disease.

The results showed that i.t. administration of O1-10 Fabs with OVA

markedly suppressed Small molecule library solubility dmso the early and/or late phases of asthmatic responses caused by passive and active sensitization. Similar results were obtained when Fabs of anti-OVA IgG2b mAb (O2B-3) were i.t. administered. In contrast, neither i.t. injection of intact 01-10/O2B-3 nor systemic injection of O1-10 Fabs suppressed the asthmatic responses. In vitro studies revealed that the capture of OVA by O1-10 Fabs prevented the subsequent binding of intact anti-OVA pAbs to the captured OVA. These results suggest that asthmatic responses may be down-regulated by the i.t. exposure to Fabs of an allergen-specific mAb via a mechanism involving the capture of allergen by Fabs in the respiratory tract before PR-171 research buy the interaction of intact antibody and allergen essential for the induction of asthmatic responses. “
“Inflammatory bowel disease (IBD) is associated with imbalances of the local intestinal immune responses, with dysregulated

CD4+ T cells contributing to the chronic inflammation. Having demonstrated altered T cell maturation in the thymus in two different mouse models of colitis, we set out to investigate whether abnormalities in T cell maturation is present in patients with ulcerative colitis (UC) or Crohn’s disease (CD). Specimens were obtained from peripheral blood (CD; n = 14, UC; n = 22), colon and PtdIns(3,4)P2 small intestinal specimens (CD; n = 6, UC; n = 13). As controls, peripheral blood specimens were obtained from healthy volunteers, patients with adenocarcinomas (n = 18) and colonic specimens from patients with adenocarcinomas (n = 14). Recent thymic

emigrants were estimated by analysis of the normalized ratio of T cell receptor excision circles (TRECs) by real-time polymerase chain reaction (PCR). The frequency of naive- and proliferating T lymphocytes and markers of extrathymic T cell maturation in the mucosa was analyzed by flow cytometry and real time-PCR. TREC levels in peripheral blood T lymphocytes were similar between IBD patients and controls. In contrast, UC patients demonstrated significantly increased levels of TRECs both in intraepithelial and lamina propria lymphocytes from the colonic mucosa compared to patients with adenocarcinomas and CD. However, markers for extrathymic T cell maturation in the mucosa were not different between controls and IBD patients. The increased TREC levels in mucosal but not peripheral blood lymphocytes in UC patients in the absence of increased extrathymic maturation in situ in the mucosa together demonstrate that recent thymic emigrants are recruited rapidly to the inflamed mucosa of these patients.

This pleads for a hypothesis in which UIP and NSIP are two different entities in one continuum.

Before discarding the role of inflammation in the pathogenesis of IPF, we first need to understand the natural history of UIP [27]. Our hypothesis www.selleckchem.com/products/epz-6438.html states the association of a SNP in the IL1RN gene with IPF predisposition; this suggests a role for IL-1 in the beginning of the pathogenetic process. The present study is one of the more expanded studies evaluating IL-1Ra and IL-1β cytokine polymorphisms and corresponding protein levels in IPF. However, a limitation of this study is that the number of IPF patients is relatively small for genetic associations. Conversely, the results are in line with previously published literature [6,28]. Although our data Tamoxifen supplier suggest no effect of age or gender on the IL-1Ra/IL-1β ratio (results not shown), more studies are needed to confirm the role of a decreased ratio in IPF. Another point that needs attention is that the rs2637988 polymorphism influenced the IL-1Ra/IL-1β ratio of but not the individual cytokine levels. The

cytokine values of IL-1Ra and IL-1β were not influenced significantly, but a mild trend is present. Carriers of the G allele had a slightly lower BALF IL-1Ra level (P = 0·21) and a higher BALF IL-1β level (P = 0·16). Although both not significant, when the ratio is calculated this effect is enhanced. A hypothetical explanation is that the balance between pro- and anti-inflammatory cytokines is of more biological importance than the absolute concentrations of IL-1Ra

and IL-1β. Carter et al. [14] showed that carriage of the IL1RN + 2018 allele 2 was associated with a reduced colonic IL-1Ra protein level and a reduced IL-1Ra/total IL-1 ratio. It is likely that in our population a similar effect is present; very however, our population might not be big enough to illustrate this with significant results, and this should be replicated in a larger cohort. In conclusion, this study showed that variation in the IL1RN associates with susceptibility to IPF. The subsequent imbalance between IL-1β and IL-1Ra might have a significant pathogenetic effect in IPF patients. Better understanding of the role of these mediators in the context of disease susceptibility and progression is important, as it may help us to find rational for newly available therapies. The authors thank Annette van der Vis, Danielle Hijdra and Jan Broess for technical and laboratory assistance. None. “
“We previously showed alterations in the thymus during experimental infection with Plasmodium berghei. Such alterations comprised histological changes, with loss of cortical–medullary limits, and the intrathymic presence of parasites.

This work was funded jointly by British Council (UK) and the Indian Government under the UK-India Education and research initiative (UK-IERI) postgraduate funding scheme. “
“Citation Mason KL, Aronoff DM. Postpartum group A Streptococcus sepsis and maternal immunology. https://www.selleckchem.com/products/cx-5461.html Am J Reprod Immunol 2012; 67: 91–100 Group A Streptococcus (GAS) is an historically important agent of puerperal infections and sepsis. The inception of hand-washing and improved hospital

hygiene drastically reduced the incidence of puerperal sepsis, but recently the incidence and severity of postpartum GAS infections has been rising for uncertain reasons. Several epidemiological, host, and microbial factors contribute to the risk for GAS infection and mortality in postpartum women. These include the mode of delivery (vaginal versus cesarean section), the location where labor and delivery occurred, exposure to GAS carriers, the altered immune status associated with pregnancy, the genetic background of the host, the virulence of the infecting GAS strain, and highly specialized immune responses associated with female reproductive tract tissues

and organs. This review will discuss the RAD001 chemical structure complicated factors that contribute to the increased susceptibility to GAS after delivery and potential reasons for the recent increase observed in morbidity and mortality. “
“Mesenchymal stem cells (MSCs) inhibit T-cell activation and proliferation but their effects on individual T-cell-effector pathways and on memory versus naïve T cells remain unclear. MSC influence

on the differentiation of naïve and memory CD4+ T cells toward the Th17 phenotype was examined. CD4+ T cells exposed to Th17-skewing conditions exhibited reduced CD25 and IL-17A expression following SPTLC1 MSC co-culture. Inhibition of IL-17A production persisted upon re-stimulation in the absence of MSCs. These effects were attenuated when cell–cell contact was prevented. Th17 cultures from highly purified naïve- and memory-phenotype responders were similarly inhibited. Th17 inhibition by MSCs was reversed by indomethacin and a selective COX-2 inhibitor. Media from MSC/Th17 co-cultures contained increased prostaglandin E2 (PGE2) levels and potently suppressed Th17 differentiation in fresh cultures. MSC-mediated Th17 inhibition was reversed by a selective EP4 antagonist and was mimicked by synthetic PGE2 and a selective EP4 agonist. Activation-induced IL-17A secretion by naturally occurring, effector-memory Th17 cells from a urinary obstruction model was also inhibited by MSC co-culture in a COX-dependent manner. Overall, MSCs potently inhibit Th17 differentiation from naïve and memory T-cell precursors and inhibit naturally-occurring Th17 cells derived from a site of inflammation. Suppression entails cell-contact-dependent COX-2 induction resulting in direct Th17 inhibition by PGE2 via EP4.

Under these circumstances it is highly likely that presentation of autoantigen also takes place in the joint. Therefore, it could be speculated that, in RA, tolDC would ideally have the ability to act in several locations: in the rheumatoid joint to anergize autoantigen-specific effector T cells locally, and in the draining lymph node to

induce Tregs from autoantigen-specific naive T cells. However, it should be noted that T cells from RA patients can be resistant to at least some tolerogenic signals; for instance, they can resist Selleck RG7204 IL-10- and IDO-mediated suppression [90, 91]. Our tolDC operate, at least partially, via a TGF-β-dependent mechanism and inhibit proliferation and IFN-γ production of peripheral blood RA T cells in vitro (unpublished data); however, whether they can inhibit autoreactive T cells in the rheumatoid joint remains to be determined. Despite the fact that our tolDC have similar ability as mature DC to process and present exogenous antigen, tolDC have lower T cell stimulatory capacity than mature DC, in line with their lower expression of co-stimulatory molecules and low production of proinflammatory cytokines [55, 82]. Moreover, tolDC induce hyporesponsiveness (‘anergy’) in antigen-experienced memory T cells while

polarizing naive T cells towards an anti-inflammatory cytokine profile [55]. We have also shown that, in a mouse in-vivo model Forskolin datasheet of collagen-induced arthritis, murine bone marrow-derived tolDC generated with Dex, VitD3 and LPS have a therapeutic effect: treatment see more of arthritic mice with tolDC (1 million cells injected intravenously three times over 8 days) reduced significantly the severity and progression of arthritis, whereas treatment with immunogenic mature DC did not reduce disease and, in fact, exacerbated arthritis [49]. Interestingly, tolDC exerted a therapeutic effect only if they had been loaded with the immunizing antigen, type

II collagen. Treatment with tolDC was associated with a reduction in Th17 cells and an enhancement of IL-10-producing T cells, and a reduction in type II collagen-specific T cell proliferation, possibly explaining their therapeutic effect. Thus, this type of tolDC is a potentially powerful tool for the treatment of RA and other autoimmune diseases. Before tolDC can be applied in a clinical trial, a protocol to generate clinical grade tolDC, compliant with current good manufacturing practice (cGMP) regulations, had to be established. For this purpose, the research-grade fetal calf serum (FCS)-containing medium was replaced with cGMP-grade medium specialized for DC (CellGro® DC medium from CellGenix, Freiburg, Germany) and LPS was replaced with MPLA, a synthetic cGMP-grade TLR-4 ligand (from Avanti Polar Lipids, Alabaster, AL, USA).

In order to control for the effect of infection on the T cell subpopulations, disease controls were recruited from the immunodeficiency clinic. These were immune-competent patients who had an increased infection burden, in whom no clinical or laboratory evidence for immunodeficiency was found. Results from this group were included only once a period of 1 year had elapsed since discharge from the clinic, to rule out an evolving immunodeficiency.

The immune tests undertaken were guided by clinical and family histories. The typical panel of tests performed included: IgG, IgA and IgM, and serum and urine electrophoresis with immunofixation if indicated. Specific antibody responses to the vaccines tetanus, pneumococcal and Haemophilius influenza B were performed, and if absent/low responses were noted the patient XL765 mouse was vaccinated and these retested after 1 month. Lymphocyte subsets, both percentage and absolute count, GDC-0068 research buy were also performed, including measurement of B cells, CD4 and CD8 T cells and natural killer (NK) cells [3,27]. At the time of analysis, all XLA and 55 of 58 CVID patients were on immunoglobulin

replacement, but not on immunosuppressive therapy. Those with autoimmune cytopenia or lymphoid interstitial pneumonia had not received corticosteroid therapy within 6 months, and only at prior doses <25 mg/kg. No patient had an affected parent, sibling or child. CVID patients

were categorized into the following clinical phenotypes, as described in Chapel et al. [2,3]: infection only (IO), enteropathy, lymphoid malignancy, polyclonal lymphoproliferation (PL), organ-specific autoimmune disease (OSAI) or autoimmune cytopenias (AC) which included immune thrombocytopenia (ITP). ITP is defined as platelets <100 × 109/l, persistent L-NAME HCl (>6 months), one episode treated with steroids [3]. The autoimmune diseases in patients in the OSAI group included: autoimmune thyroid disease (n = 5), psoriasis (n = 6), uveitis (n = 2), vitiligo (n = 2), pernicious anaemia (n = 3), ulcerative colitis (n = 4) and type 1 diabetes (n = 2). Only one patient had a subsequent lymphoid malignancy and only three had an enteropathy, so these categories were not utilized in the analysis; these patients were included in the CVID total group. Figure 1 demonstrates the distribution of clinical phenotypes of the CVID patient group. The number of patients stated in each group in Table 1 is the maximum number of patients analysed for a T cell subpopulation. However, for some of the T cell subpopulations smaller numbers were analysed due to either technical difficulties with a particular tube or limited sample availability. All flow cytometric analysis was performed on ethylenediamine tetraacetic acid (EDTA) blood samples within 48 h of venepuncture.

2), and n = 3 (exp. 3) mice per group. For day 60 p.i., cytokine production and parasite burden in

IL-10FL/FL Cre− and IL-10FL/FL CD4-Cre+ were compared in two independent experiments using n = 3 (exp. 1) and n = 6 (exp. 2) mice per group and IL-10FL/FL Cre− and IL-10FL/FL CD19-Cre+ were compared in two independent experiments using n = 5 (exp. 1) and n = 5 (exp. 2) mice per group. Spleen cells were prepared from naive and infected mice at indicated time points after infection. A total of 5 × 105 spleen cells were cultivated in 96-well round bottom plates for 72 h at 37°C and 5% CO2 in RPMI 1640 medium supplemented with 10% FCS, l-glutamine (2 mg/mL), and gentamycin (50μg/mL). For stimulation, cells were either incubated with medium, 1 μg/mL anti-CD3 (145–2C11) or 12.5 μg/mL L. sigmodontis Ag (LsAg) (prepared as described [20]) in quadruplicates. Supernatants were collected Selleckchem Regorafenib and Vorinostat mw stored at -20°C until analysis. Cytokine concentrations in culture supernatants from spleen cells were quantified by ELISA (R&D Systems, Wiesbaden, Germany) according

to the manufacturer’s instructions. To measure proliferation cell cultures were labeled with 3H thymidine (0.25 μCi/well) and cultured for additional 18–20 h. Plates were frozen until detection of 3H thymidine uptake. The Fc receptors of spleen cells were blocked with Cohn II (Sigma Aldrich) for 10 min on ice. For surface staining, cells were stained with 1:100 dilutions of anti-CD3e-allophycocyanin (clone 145–2C11) and anti-CD49b-PE (clone DX5), with 1:250 dilutions of anti-CD4-allophycocyanin (clone GK1.5), anti-CD4-FITC (clone RM4.5), anti-CD8a-allophycocyanin (clone 53–6.7), anti-CD8a-PerCP cyanine-5.5 (PerCP Cy5.5) (clone 53–6.7), anti-CD11b-allophycocyanin (clone M1/70), anti-CD11c-allophycocyanin (clone N418), and anti-CD19-allophycocyanin (clone 1D3) or with 1:500 dilutions of anti-Gr-1-Alexa Etoposide Fluor 488 (clone RB6–8C5) and CD11b-PerCP Cy5.5 (clone M1/70) purchased from BioLegend (Aachen, Germany), BD Biosciences (Heidelberg, Germany), or eBioscience (San Diego, CA) as indicated for 30 min on ice. Foxp3 expression was determined using

PE–anti-mouse Foxp3 Staining Set (eBioscience) according to the manufacturer’s instructions. Samples were analyzed on a FACSCalibur Flow Cytometer (Becton Dickinson, Mountain View, CA) using Cell Quest software. All statistical tests were performed by ANOVA with Bonferroni posttest using Prism software (GraphPad Software, San Diego, CA). p values below 0.05 were considered statistically significant. I.H. is funded by the Werner-Otto-Stiftung. A.H. and S.S. are funded by the Deutsche Forschungsgemeinschaft SFB 704. We thank Matthias Haury and Dinis Calado for providing the IL-10-eGFP reporter mouse strain. The authors declare no financial or commercial conflict of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors.

The electrophoretic mobility shift assay was performed as described previously [5]. The consensus sequence-specific oligo-nucleotide probes were end-labeled with γ-32P-ATP

according to the manufacturer’s recommendations. The oligonucleotide with the C/EBP consensus binding sequence used were 5′-GGTTCTTGCGCAACTCACTGAA-3′ and 3′-TTCAGTGAGTTGCGCAAGAACC-5 For SRT1720 purchase the binding reaction, 2 ng labeled oligonucleotide (approximately 20 000 cpm) and 2 μg poly dIdC (Amersham Pharmacia Biotech) carrier were incubated with 2 μg nuclear protein in a binding buffer (10 mM HEPES, 60 mM KCl, 1 mM DTT, 1 mM EDTA, 7% glycerol, and pH 7.6) for 30 min at room temperature. DNA–protein complexes were resolved on 6% nondenaturing polyacrylamide gels and visualized by exposure to autoradiographic films. Sprague-Dawley rats (230–250

g) were anesthetized by i.p. injection of chloral hydrate (400 mg/kg), positioned in a stereotaxic apparatus, and either LPS (from Salmonella enteritidis; Sigma, St. Louis, MO), IL-13, IL-13 antibody, or a combination of 2–3 were stereotactically injected into the right cerebral cortex (AP+4.8 mm ML, −5.5 mm, DV −6.0 mm from the bregma) according to Paxinos’ atlas. selleck chemicals llc The animals were categorized into to five groups: group I, PBS injection (30 μL); group II, LPS injection (10 μg); group III, IL-13 (100 μg) injection; group IV, LPS (10 μg) + IL-13 (100 μg) injection; and group V, LPS (10 μg) + IL-13 (100 μg) + IL-13 neutralized antibody (NA, 10 ng) in a final volume of 30 μL PBS injected at a rate of 0.15

μL/min using a 26-gauge Hamilton syringe attached to an automated pump Grape seed extract and left in situ for an additional 5 min to avoid reflux along the injection tract. A 1.5 m diameter, 45 cm deep Morris water maze was filled with water to a depth of 26.5 cm. The water temperature was kept at 26 ± 2˚C. A circular platform, 25 cm high, and 12 cm in diameter was placed into the tank at a fixed location in the centre of one of four imaginary quadrants. Approximately 1.5 L of milk was used to make the water opaque. The rat was then guided to swim to the platform. Activity in the water maze was recorded using a CCD camera on the ceiling above the centre of pool, which was attached to an automated tracking system (Noldus, Netherlands). A single experiment was performed with three rats. Behavioral measures included latency to targets, swing speed (cm/s), number of platform crosses, and percent time within the targeted area. Percent time in appositive object in reversal trial and in targeted object in extinction test was also conducted. Data were analyzed by Etho Vision 3.1. The animals were transcardially perfused with a saline solution containing 0.5% sodium nitrate and heparin (10 U/mL), followed by 4% paraformaldehyde dissolved in 0.1 M phosphate buffer (PB).