14 There is a strong association between high UF rates INK 128 order and the incidence of IDH.15

High UF rates are often the product of short dialysis times restricting conventional HD. They are further exacerbated by patient comorbidities, cardiovascular disease and autonomic instability, high intra-dialytic weight gain and the prescription of multiple antihypertensive medications. The importance of the UF rate in the aetiology of IDH is highlighted by the lower incidence of IDH observed in short daily and nocturnal home HD patients.16 More frequent treatments result in lesser intra-dialytic weight gains and therefore a lower rate of UF per treatment. This avoids the excessive falls in plasma volume associated with higher UF rates. The dry weight or IBW can be simply defined as the lowest weight tolerated by the patient without manifesting any symptoms, and is in theory analogous to the patient’s normal physiological weight. In clinical practice IBW and the target UF volume are usually determined by the clinical assessment of fluid status and degree of inter-dialytic weight gain. While clinical assessment is adequate in determining the IBW in most situations, it is unable to predict which patients will develop IDH and the onset of episodes in these patients. Modulation of blood volume has been developed to allow better assessment of IBW and to predict learn more and prevent episodes

of IDH. BVM devices (such as Crit-line® or Hemoscan®) use light to continuously measure haematocrit or haemoglobin values. A reduction in BV results in a greater concentration of haematocrit or haemoglobin and a lesser passage of light.17,18 The relative blood volume (RBV) is a measure of the

BV at a given time and is expressed as a percentage of the volume at the commencement of treatment.19 With volume overload, there is a relatively small change in RBV with fluid removal and therefore fluid removal is usually well tolerated. As the patient approaches IBW, there are more significant changes in RBV with equivalent UF prescriptions. It is the slope of the RBV curve rather the absolute value that can provide information about the patient’s haemodynamic stability.20 The concept of a critical RBV that predicts IDH was found to click here vary markedly from patient to patient, and between treatments in the same patient.21 Early studies demonstrated that the RBV curve decreases more rapidly in dialysis sessions with IDH,22 and that changes in RBV can be used to predict and therefore prevent episodes of IDH.23,24,25 Several small studies have suggested BVM devices may be useful to predict IDH and allow intervention to prevent subsequent episodes (Table 1).27,28,30 In a prospective, randomized cross-over trial of 12 IDH-prone patients, BVM was compared with conventional dialysis monitoring.28 The incidence of IDH in patients having dialysis sessions using BVM was 33.3%, compared with 81.

IFN-β-mediated immunomodulatory functions may differentially operate depending on the responding cell subset acting on T- or B-cell proliferation, GPCR Compound Library solubility dmso modulation of cytokine production, and regulation of adhesion molecules involved in lymphocyte migration across the blood-brain barrier [18]. For these reasons, investigating the action of IFN-β therapy on B cells might be of great relevance to understand

their pathogenic role in the development and regulation of autoimmune inflammatory response in MS. There is increasing recognition that TLRs and TLR-driven responses can play a key role in the pathogenesis of several autoimmune diseases, including MS. TLR7 and TLR9 are selectively expressed by B cells, and when activated by specific ligands, lead to their proliferation and differentiation into Ig-secreting cells. Given the key importance of B lymphocytes in MS disease, we investigated whether IFN-β therapy would modulate Ig synthesis in MS patients by performing a longitudinal study conducted with unseparated PBMCs isolated from 15 Cell Cycle inhibitor MS patients before (T0) and

1 month after (T1) the beginning of IFN-β therapy. Moreover, PBMCs isolated from 10 healthy donors (HDs) were also included in this study as comparative control. To this end, PBMCs were cultured in vitro with either a specific TLR7 (the synthetic small molecule

3M001) or TLR9 (a type B CpG, 2006) agonist for 7 days and then IgM (Fig. 1A) and IgG production were Aspartate evaluated by Elispot (Fig. 1B) and Elisa assay (Supporting Information Fig. 1). The TLR9-mediated B-cell stimulation led to a similar frequency of IgM- and IgG-secreting cells in both HD- and MS-affected individuals and this Ab release was not modified in response to IFN-β treatment. On the other hand, it was very interesting to find that the basal level of TLR7-induced Ig production was significantly lower in MS patients as compared with that in HD, showing a specific defect in TLR7 responses in B cells from MS sufferers. Surprisingly, 1 month of IFN-β therapy was able to partially restore this deficiency and selectively increase the production of IgM and IgG upon TLR7 triggering, re-establishing the level of Ab release found in HDs. The analysis of Ig content by Elisa confirmed the results obtained by Elispot assay (Supporting Information Fig. 1). IFN-β-mediated effect was long-lasting since it was still observed after 6 months of IFN-β treatment (data not shown). However, IFN-β did not enhance auto-Ab production as demonstrated by measurement of both homogeneous and speckled patterns of anti-ANA Abs on sera of MS patients before and after therapy (data not shown) [19].

As judged by morphological criteria and Turk colourant find more staining, more than 90–95% of the adherent cells were macrophages. The biological activity of TNF-α was

determined using a sensitive actinomycin D-treated murine L-929 fibroblast assay, as described previously [35]. Briefly, L-929 cells were plated in 96-well plates (Costar) at 1·8×104 cells/well in 0·1 ml and allowed to grow to near confluence overnight at 37°C in 95% air, 5% CO2. Serially diluted macrophage supernatants were added to the L-929 cells. After 18 h of incubation in the presence of 10 µg/ml actinomycin D (Amersham Biosciences, Piscataway, NJ, USA), the plates were washed with PBS and viable cells were fixed and stained with violet crystal solution (0·1% in 20% methanol) for 20 min at 37°C. Then, absorbance of the blue colour extracted with 30% acetic acid was measured with a microtitre plate reader (Organon Tecnika, C.A. Buenos Aires Argentina) at 550 ηm. The activity titre of TNF-α in lytic units/ml (LU50/ml) was calculated from the reciprocal of the dilution necessary for 50% cell lysis. Plasma were collected and frozen at −20°C until use. TNF-α and IL-10 ELISA were performed on flat-bottomed polystyrene microtitre plates (OptEIA set; BD Biosciences,

San Diego, CA, USA) according to the Dabrafenib manufacturer’s instructions. The antibody response to SRBC was evaluated through a haemagglutination assay. Briefly, serum samples were inactivated at 56°C for 30 min and diluted in a double dilution test using PBS–bovine serum albumin (BSA) 0·2%. Then, 50 µl of each dilution was dispensed in a round-bottomed 96-well microplate and 50 µl of 0·25% SRBC in PBS–BSA was added. Finally, the plates were incubated for 24 h at room temperature and the titre was considered as the reciprocal of the last positive dilution. To measure mouse IgG and Glycogen branching enzyme IgM, anti-SRBC serum samples were prepared at different dilutions in PBS–BSA 0·5%. Then, 10 µl of serum were incubated with 3 µl of

1% SRBC (PBS–BSA 0·5%) for 30 min at 4°C. The cells were washed three times and (PE) anti-IgM or (FITC) anti-IgG was added and incubated for 30 min at 4°C. Cells were washed and immunoglobulins were evaluated in a Becton Dickinson FACScan using CellQuest software (Becton Dickinson, San Jose, CA, USA). Controls of SRBC incubated with labelled antibodies in the absence of serum were also carried out. Values are expressed as the mean ± standard error of the mean (s.e.m.) of n observations. The statistical significance of differences between TNF-α samples measured by the L-929 bioassay was determined using the non-parametric Friedman test followed by Wilcoxon’s signed-rank test. ELISA and haemagglutination assays were analysed using the Mann–Whitney unpaired test. All statistical tests were interpreted in a two-tailed fashion and P < 0·05 was considered significant. A daily i.p.

The most robust

human immune model is generated by implantation of human fetal thymic and liver tissues in irradiated recipients followed by intravenous injection of autologous fetal liver haematopoietic stem cells [often referred to as the BLT (bone marrow, liver, thymus) model]. To evaluate the non-obese diabetic (NOD)-scid IL2rγnull (NSG)–BLT model, we have assessed various engraftment parameters and how these parameters influence the longevity of NSG–BLT mice. We observed that irradiation and subrenal capsule implantation of thymus/liver fragments was optimal for generating human immune systems. However, after 4 months, a high number of NSG–BLT mice develop a fatal graft-versus-host disease (GVHD)-like syndrome, which correlates with the activation of human T cells and increased levels of human immunoglobulin (Ig). Onset of GVHD was not delayed in NSG mice lacking murine major histocompatibility find more complex (MHC) classes I or II and was not associated with a loss of human regulatory T cells or absence of intrathymic cells of mouse origin (mouse CD45+). Our findings demonstrate that NSG–BLT mice develop robust human immune systems, but that the experimental window for these mice may be limited by the development of GVHD-like

pathological changes. Immunodeficient mice engrafted with human immune systems represent a promising alternative for the in-vivo study of human immune systems without www.selleck.co.jp/products/AG-014699.html placing patients at risk [1-4]. These ‘humanized’ mice are created by the engraftment of immunodeficient mice with mature human immune cell populations, human Alectinib in vivo haematopoietic stem cells (HSC) or human fetal tissues [5-7]. Early humanized models using immunodeficient mice bearing the Prkdcscid (scid) recombination activating gene

1 (Rag1null) or 2 (Rag2null) mutations were limited by low levels of systemic engraftment of human immune cells, variability in the overall levels of human cell survival and limited functionality of the human immune system [8]. The limitations of these initial immunodeficient mouse models were largely overcome by the introduction of targeted mutations in the interleukin (IL)-2 receptor common gamma chain (IL2rg) gene [8]. The IL-2rγ-chain is required for high-affinity ligand binding and signalling through multiple cytokine receptors, including those for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 [9]. Immunodeficient mice bearing a targeted mutation within the IL2rg gene support higher levels of human haematolymphoid engraftment than all previous immunodeficient stocks and permit the engraftment of functional human immune systems [10-19]. Although a number of engraftment strategies are currently being used to produce humanized mice [8], the implantation of human fetal thymic and liver tissues accompanied by intravenous (i.v.

cRNA preparation, purification and labelling, array hybridisation and scanning were performed Saracatinib in vitro according to the manufacturer’s protocol (Illumina). Gene expression was compared between (I) tumour spheroids, (II) tumour cells only sorted out from co-cultures

and (III) co-culture spheroids. Four biological replicates (monocytes from different donors) for co-culture spheroids and two replicates for tumour spheroids were studied using Illumina HumanRef-8 v.2.0 chips. Illumina BeadStudio was used for background correction and generating average signal intensity. R/Bioconductor 30 was used for quantile normalisation 31. Probes showing low variability were discarded by applying interquartile filter (IQR=0.25). A linear model 32 was employed by controlling the number of false positives by false discovery rate (FDR) with adjusted p-value of ≤0.05 33. A log2 fold change signal threshold (log2(FC)≥1.0) was applied for comparison of (I) and (II), and (log2(FC)≥1.5) for comparison of (II) and (III). MultiExperiment Viewer 34, 35 was used for hierarchical clustering, setting a Euclidean Nutlin-3a cell line distance as the measure of dissimilarity and average linkage as the linkage method. To identify biologically relevant regulatory processes and pathways, MetaCore with a FDR adjusted p-value of ≤0.05 was used. Primers were designed using Primer-3 (Supporting Information Table 3). Real-time

PCR was performed with Stratagene Mx3000P (Agilent). All gene expressions were normalised to Selleckchem Pembrolizumab housekeeping gene hypoxanthine phosphoribosyltransferase (HPRT). Tumour cells were labelled with anti-EpCAM-FITC, stained with propidium iodide (15 μg/mL; Sigma) and analysed by flow cytometry. Pre-cleared cell culture supernatants

(days 5–8) were used for cytokine measurement (Bio-Plex Pro Human Cytokine Groups I and II, BioRad). Culture medium with 5% HS was used as blank and diluent. Detection was carried out with Luminex 200TM. Results were acquired using IS 2.3 software. CCL8 and CCL13 were detected using Duoset ELISA Development Systems (R&D Systems). Samples were diluted and prepared according to manufacturer’s protocol. Culture medium with 5% HS was used as the blank. Supernatants were incubated at 37°C, 5% CO2, 30 min to allow pH equilibration before assay. Total white blood cells (WBC) were obtained from buffy coats after red blood cell lysis. Totally, 7.5×105 WBC were seeded onto cell culture inserts (BD) with 8.0 μm pore sizes, incubated with supernatants in wells for 1 h. T cells (CD3, CD4, CD8) that trans-migrated through the inserts were distinguished by fluorescence labelling and analysed by flow cytometry (LSRII, BD). Countbright beads (Invitrogen) were used for cell number quantification. WBC from six donors and supernatants from three replicates (spheroid cultures) were used. Tumour cells from co-culture spheroids were labelled with anti-EpCAM-FITC followed by anti-FITC microbeads (Miltenyi) for magnetic sorting into tumour cells and TAMs.

Streptococcus salivarius DSM 23307, characterized in this study, is sensitive to the main antibiotics used for the treatment of URTIs, does not possess dangerous enzymatic reactions, as demonstrated by its metabolic profile, and lacks the main streptococcal virulence genes, that is, sagA, smeZ-2, and speB. All this is further proof of its virtuous nature. Moreover, a fundamental property of this strain is its strong BLIS activity against S. pneumoniae including virulent and multidrug resistance strains such as the most diffused serotypes circulating in our country

involved in severe infections in children and adults (Resti et al., 2010; Ansaldi et al., 2011); furthermore, it does not interfere with other S. salivarius strains. The BLIS activity of S. salivarius DSM 23307

is not associated with typical streptococcal bacteriocin genes such as salA, sboB, srtA, scnA, and sivA as demonstrated by PCR experiments, Gemcitabine research buy suggesting the presence of variant or different antimicrobial peptide genes. These molecular data correlated with its unusual inhibitory spectrum primarily oriented BMS-907351 price versus S. pneumoniae and only in particular growth conditions, that is, in TSYCa versus S. pyogenes. The strong in vitro capacity to inhibit S. pneumoniae resembles the BLIS activity of the nisin inhibitory spectrum (Goldstein et al., 1998), even if the RNA Synthesis inhibitor presence of this gene was excluded. Another essential characteristic of strains for use as bacterial replacement therapy is their capability to adhere to host tissues: the cells of S. salivarius DSM 23307 remained attached to the HEp-2 monolayer demonstrating a good adherence capacity. In conclusion, in this study, we identified one strain as a potential oral probiotic, possessing desirable characteristics for bacteria-therapy: S. salivarius DSM 23307 possesses a strong activity against S. pneumoniae and is harmless to other S. salivarius strains, it is non-pathogenic for the host as demonstrated by safety assessment and

it efficiently adheres to human larynx cells. Further studies on S. salivarius DSM 23307 are ongoing both to completely characterize the antimicrobial peptides and to confirm its probiotic use in humans. This work was supported in part by DMG Italia s.r.l. and by research funding of S.S. and M.S. The authors thank Antony Bridgewood for the language revision. “
“Programmed death-ligand 1 (PD-L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death-1 (PD-1). However, the mechanism of PD-L1-mediated inhibitory signalling after PD-L1 cross-linking by anti-PD-L1 monoclonal antibody (mAb) or PD-1–immunogloblin fusion protein (PD-1-Ig) is still unknown, although it may induce cell death of PD-L1+ cells required for regular immune reactions.

Given the enormous morbidity and mortality associated with these devastating diseases, the potential impact of vitamin D supplementation at a population level is staggering and is certainly worthy of further investigation in well-designed clinical trials. G. D and G. E. conceived the idea of the review. G. D., S. K., J. K., S. R., and G. E. drafted the manuscript and critically reviewed the content. G. D. is supported by the AANF/CMSC

John F. Kurtzke Clinician-Scientist Award, a Goodger Scholarship (University of Oxford), and the NIHR Biomedical Research Centre, Oxford. None. “
“Tauopathies are clinically, morphologically, and biochemically this website heterogeneous neurodegenerative diseases characterised by the deposition of abnormal tau protein in the brain. The neuropathological phenotypes are distinguished based on the involvement of different anatomical areas, cell types and presence of distinct isoforms of tau in the pathological deposits. The nomenclature of primary tauopathies overlaps with the modern classification of frontotemporal lobar degeneration. Neuropathological phenotypes comprise Pick`s disease, progressive supranuclear palsy,

corticobasal degeneration, argyrophilic grain disease, primary age-related tauopathy (PART), formerly called Acalabrutinib purchase also as neurofibrillary tangle-only dementia, and a recently characterised entity called globular glial tauopathy. Mutations in the gene encoding the microtubule associated protein tau (MAPT) are associated with frontotemporal dementia and parkinsonism linked to chromosome 17. In addition, further neurodegenerative conditions with diverse aetiologies may be associated with tau pathologies. Thus the spectrum of tau pathologies and tauopathy entities expands beyond the traditionally discussed disease-forms. Detailed ADP ribosylation factor multidisciplinary studies are still required understand their significance. “
“Since cystatin C (CysC) in involved in some forms of neurodegeneration, we investigated

the possible relationship between CysC and multiple system atrophy (MSA), including its parkinsonian (MSAp) and cerebellar (MSAc) phenotypes. Cystatin C gene (CST3) haplotypes were determined by PCR followed by KspI digestion in 50 MSA patients and 108 controls. CST3 and cathepsins B, D and L1 mRNA levels were studied in frozen post-mortem caudate nucleus and cerebellar samples of 8 MSAp, 4 MSAc and 18 control brains and analyzed by the deltadeltaCt method. CysC immunohistochemistry was performed on 3 MSAp, 3 MSAc and 3 control cerebella. Additionally, determination of CST3 and cathepsins B, D and L1 mRNA levels and immunohistochemistry for CysC were carried out in cerebella from 3 patients with paraneoplastic cerebellar degeneration, 3 with spinocerebellar ataxia (type 3, SCA3) and 3 with cerebellar ischemia (CI). In the set of blood samples, the CST3 B-haplotype was associated with MSAp (OR 4.86, CI 1.84-13.3).

One of the advanced lipid-based delivery systems is the solid–lipid nanoparticles (SLNs), which can be one of the alternative delivery system to electroporation. SLNs are basically composed of high-melting-point lipids that act as a solid core, covered by surfactants. The use of materials that are generally recognized as safe (i.e. triglycerides, partial glycerides, fatty acids, steroids) [35] leads to an advantageous toxicity profile [36].The SLN production by hot high-pressure homogenization is easy, and no organic solvents are required [37]. Scaling-up is standardized up to 50-kg batches [38], and steam sterilization is possible [39]. The excellent activity and superiority of DOTAP–cetyl palmitate–SLN were reproducible.

The positively charged SLN would bind to polyanionic DNA via electrostatic

force leading Epigenetics inhibitor to SLN–DNA complex that will protect DNA from interaction with small molecules in the environment and will be taken into cell by an endocytosis process [40]. An additional advantage of delivering vaccine candidates by nanoparticles is the potential to enhance their stability during transport, and this is critical in areas that lack reliable cold storage chain (2–8°C) [41]. Our previous results revealed that stable formulation of cSLN was able to protect pDNA in DNase I challenge assay and deliver it to the right immune cells for the proper immune response induction [22]. In this study, we generated a DNA vaccine encoding A2–CPA–CPB−CTE as a trifusion gene and compared the impact of DNA vaccine delivery to immune cells (e.g. physical/electroporation vs. chemical/cSLN formulation) on the development of protective immune response against an infectious Navitoclax purchase L. infantum challenge. The pcDNA–A2–CPA–CPB−CTE was formulated into cationic

lipid particles with nanometre Bay 11-7085 range (~240–250 nm). In our experimental system, the administration of pcDNA–A2–CPA–CPB−CTE in BALB/c mice elicited the induction of specific Th1 and Th2 clones, indicating a mixed immune response and the production of IFN-γ and IL-10, although IFN-γ was much higher than IL-10, especially in G2 using the cSLN formulation. However, a higher amount of IFN-γ was obtained in G1 immunized via electroporation in response to both rA2–rCPA–rCPB and F/T L. infantum antigens at 4 and 8 weeks after challenge. Although IFN-γ secretion at 8 weeks after challenge in G1 was higher than in G2, there were no significant differences in IFN-γ: IL-10 ratio between these two groups. Also, at 8 weeks after challenge, the IFN-γ: IL-10 ratio in splenocytes from mice immunized with pcDNA–A2–CPA–CPB−CTE (G1 and G2) stimulated with rA2–rCPA–rCPB was significantly higher than G3 (~28·25- and 26·5-fold; P < 0·01) and G4 (~8·69- and 8·154-fold; P < 0·01). The same result was obtained with splenocytes stimulated by F/T L. infantum antigen. So, we can conclude that these two delivery strategies elicit the same immune responses with efficient protection.

“
“Although some patients with diabetic nephropathy with overt proteinuria have microscopic haematuria, the pathological characteristics and clinical significance related to microscopic haematuria have not yet been clarified. The aim of the present

study was to clarify the pathological characteristics and clinical significance of microscopic haematuria. Eighty-four type 2 diabetes patients with overt proteinuria and biopsy-confirmed diabetic nephropathy were enrolled. The clinical and histological findings were compated between the patients with persistent haematuria (group 1, n = 25) and those with persistent non-haematuria (group 2, n = 23) after renal biopsy. The association between persistent haematuria and renal outcome

at 5 years was examined. Histological scoring was made according to the original system and that of Tervaert et al. Thirty-six MI-503 concentration patients (43%) had microscopic haematuria at the time of renal biopsy. Age was significantly smaller and blood pressure was significantly greater in group 1 than see more in group 2 (age: group 1, 56 ± 10 years; group 2, 62 ± 9 years; P = 0.03, systolic blood pressure: group 1, 152 ± 16 mmHg; group 2, 140 ± 16 mmHg; P = 0.01). There were no significant differences in histological parameters between the two groups. A logistic regression model demonstrated that arteriolar hyalinosis was significantly associated with persistent haematuria (OR = 2.81; P = 0.04). There were no significant differences in changes in reciprocal serum creatinine and rates of doubling of serum creatinine after renal biopsy between the two groups. Although those arteriolar hyalinosis was

associated with persistent haematuria, the clinical significance of microscopic haematuria was minor in diabetic nephropathy in type 2 diabetes patients with overt proteinuria. “
“Aim:  Peritoneal dialysis patients with ultrafiltration failure frequently have fluid overload. It is known that the increase in the ultrafiltration is associated with decrease in the left ventricle (LV) dysfunction. This study was designed to examine the potential effects of serum brain natriuretic peptide (BNP) on cardiac functions and to determine the relationship between BNP and cardiac parameters in continuous ambulatory peritoneal dialysis (CAPD) patients with ultrafiltration failure. Methods:  Twenty-eight patients with high or high-average membrane permeability as indicated by the peritoneal equilibration test were enrolled and randomized to receive either once or twice daily icodextrin. Serum BNP levels and echocardiographic measurements were evaluated at baseline and at the end of the eighth week. The correlations between the percentage changes of parameters from baseline were also studied. Results:  In both groups there was a significant decrease in serum BNP, LV mass, heart rate (HR) and cardiothoracic index (CTI) and an improvement in ejection fraction (all P < 0.05).

The enrichment objects can include various ‘toys’ of different find more shapes, sizes, colours, textures and smells, as well as specific facilitators of physical activity, such as tunnels, ladders, ropes and running wheels. This enhancement of sensory, cognitive and motor

activity is thought to stimulate neural activity across a range of central (and peripheral) systems, and a variety of subsequent cellular and molecular changes, which will be discussed below. Environmental enrichment is a relative term, defined in the context of ‘standard housing’, which varies between laboratories. Standard housing for laboratory rodents often includes minimal objects (apart from bedding and nesting material) added to the Smoothened Agonist home cage and might therefore be considered a form of sensorimotor deprivation [1]. This may impact on the ‘environmental construct validity’ of standard-housed preclinical models of brain disorders and have implications for clinical translation, as discussed recently [2,3]. Nevertheless, it is the difference between ‘enriched’ and ‘standard’ conditions which is crucial for such laboratory animal studies, allowing the experimenter to define EE-induced changes to brain structure and function, as well as molecular and cellular correlates. The first description of environmental enrichment of experimental animals

was by the pioneering neuroscientist (-)-p-Bromotetramisole Oxalate Donald Hebb, involving free-roaming rats in a home environment, relative to standard-housed caged controls [4]. Since Hebb’s first description, a wide variety of EE experiments have been performed using laboratory mice and rats. These EE effects on wild-type rodents have been reviewed extensively [1,5,6] and therefore will only be discussed briefly in the present article. However, key aspects of the reproducible effects of EE on wild-type rodents include cognitive enhancement, enhanced synaptic plasticity, adult hippocampal neurogenesis, synaptogenesis and modulation of gene expression [7]. Furthermore, following the

review of EE effects in animal models of brain disorders, I will briefly discuss potential mechanisms suggested by studies in wild-type rodents. The first evidence that EE could be beneficial in a genetic model of a brain disorder was provided using Huntington’s disease transgenic mice [8], as discussed in a later section. This was followed up with EE studies in animal models other neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease [9], which will be reviewed in detail below. Furthermore, EE has also been found to induce beneficial effects in animal models of a range of other CNS disorders, including depression [10–12], epilepsy [13–15], stroke [16–18], multiple sclerosis [19], addiction [20,21], schizophrenia [22], autism spectrum disorders [23–25] and other neurodevelopmental disorders [26,27].