Non-thermal near infra-red (IR) has been shown to have many beneficial photobiological effects on a range of cell types, including neurons. In the present study, a pretreatment with a daily 6
min ...exposure to IR1072 for 10 days yielded a number of significant behavioral effects on middle-aged female CD-1 mice (12-months) tested in a 3D-maze. Middle-aged mice show significant deficits in a working memory test and IR treatment reversed this deficit. Interestingly, the IR treated middle-aged group despite making less memory errors than sham middle-aged group spent longer time in different parts of the maze than both the young group (3-months) and sham-middle-aged group (12-months). Young mice appeared more anxious than middle-aged mice in the first sessions of the test. Exposure to IR appeared to have no significant effects upon exploratory activity or anxiety responses. However, it elicited significant effects on working memory, with the IR middle-aged mice being more considerate in their decision making, which results in an overall improved cognitive performance which is comparable to that of young CD-1 mice. The present study describes a novel method for assessing emotional responses and memory performance in a 3D spatial navigation task and demonstrates the validity of our new all-in-one test and its sensitivity to ageing and non-invasive beneficial IR treatment.
Three set of experiments were performed in an enclosed space (open-field) and in an open space (elevated platform). The surface of the open-field and the elevated platform were divided in nine equal ...squares. Rats were exposed (without previous habituation) in a unique session (experiment 1) or three consecutive sessions (experiment 2) either to an open-field (enclosed space) or to an elevated platform (open space) with and without an object on the centre of the field. In experiment 3, rats were exposed (without previous habituation) either to an enclosed or an open space on five consecutive sessions, one session a day. They were tested in an object recognition test in sessions 1, 3 and 5. In sessions 2 and 4, no objects were present. In experiment 1, we recorded the latency, frequency and duration of entries into different areas of the field. In experiment 3, we recorded the latency, frequency and duration of contacts with objects in addition to entries into different areas of the field.
The first experiment demonstrates that rats exposed for the first time to an enclosed or an open space do not express neophobia toward novel objects in the absence of walls that surround an open-field. They crossed frequently into and spent more time in areas occupied with an object than in unoccupied areas. After two sessions of habituation to an empty open space or an empty enclosed space, the latency of first approach to a novel object is reduced while the frequency and duration of approaches are increased. The third experiment on object recognition confirmed that rats do not avoid novel objects; they made frequent visit and spent more time in the corner of the field occupied with an object than in empty corners. Recording of crossings provided detailed information about the patterns of exploratory behavior of rats but failed to reveal discrimination between novel and familiar objects which was evident in both open and enclosed space with recording of contacts with objects on the fifth exposure.
Exposure to novelty has been shown to induce anxiety responses in a variety of behavioural paradigms. The purpose of the present study was to investigate whether exposition of naïve rats to novelty ...would result in a comparable or a different pattern of responses in an open space versus enclosed space with or without the presence of an object in the centre of the field. Lewis and Wistar rats of both genders were used to illustrate and discuss the value and validity of these anxiety paradigms. We examined a wide range of measures, which cover several aspects of animals’ responses.
The results of this study revealed significant differences between the behaviour of animals in an open space and in the enclosed space. It also revealed significant differences in animal's responses to the presence and absence of an object in the open space and in the enclosed space.
In the enclosed space, rats spent most of their time in the outer area with lower number of exits and avoided the object area except when there was an object, while in the open space rats displayed frequent short duration re-entries in the outer area and spent longer time in the object area in presence of an object. The time spent in the inner area (away from the outer area and the object area) was significantly longer and the number of faecal boli was significantly higher in the open space than in the enclosed space.
In the present report, we will discuss the fundamental differences between enclosed space and open space models, and we will examine some methodological issues related to the current animal models of human behaviour in anxiety. In the enclosed space, animals can avoid the potential threat associated with the centre area of a box and chose the safety of walls and corners, whereas, in the open space animals have to avoid every parts of the field from which there was no safe escape. The response of animals to novelty in an open space model appears more relevant to anxiety than in an enclosed space. The present studies revealed no correlations between the measures of behaviour in enclosed space and the measures of behaviour in open space, which suggest that these two models do not involve the same construct. Our results suggest that the enclosed space model involves avoidance responses while the open space model involves anxiety responses. The open space model can be very useful in understanding the underlying neural mechanisms of anxiety responses, and in assessing the effects of potential anxiolytic drugs.
The NMDAR2B subunit is the focus of increasing interest as a therapeutic target in a wide range of CNS pathologies, including acute and chronic pain, stroke and head trauma, drug-induced dyskinesias, ...and dementias. Due to significant pharmaceutical endeavor, an impressive collection of chemical leads has been developed which target the NR2B subunit, some of which appear to discriminate between closely related subtypes. We now have the benefit of a structural template for the ifenprodil binding site which should further improve future structure activity relationships. A growing appreciation of the likely extrasynaptic localisation of the NR2B receptor subtype and importance of NR2B protein modification, notably tyrosine phosphorylation, may explain its therapeutic importance. The apparent superior preclinical and clinical data for the second and third generation NR2B compounds is likely to reflect subtype selectivity, a unique mode of action and cellular location of the NR2B receptors in the CNS.
•Common to hypertension and pregnancy is exaggerated sympathetic activity.•Characterisation of the GABAA receptor expression in the PVN.•Significant decrease in α5 subunit GABAA receptor in the ...PVN.•Altered α5 subunit GABAA expression may be a contributor to sympatho-excitation.
A characteristic of both hypertension and pregnancy is increased sympathetic nerve activity. The level of sympathetic activation is determined, in part, by a tonic GABAergic inhibition arising from the hypothalamic paraventricular nucleus (PVN). In hypertension, decreases in GABAergic inhibition and increases in glutamatergic excitation within the PVN contribute to this sympatho-excitation. In late-term pregnancy however, the sympatho-excitation appears to be mediated by decreases in GABAergic inhibition only. This study examined whether changes in subunit expression for GABAA receptors in the PVN could provide a molecular basis for the sympatho-excitation characteristic of hypertension and pregnancy. Hypertension and pregnancy were accompanied by significant decrease in the GABAA receptor α5 subunit in the PVN. We suggest that decreases in the α5 subunit of the GABAA receptor may be important in mediating the sympatho-excitation observed in both hypertension and pregnancy.
In the present report we describe the behavior of two albinos (BALB/c and CD-1) and one pigmented (c57/BL6) strains of mice exposed to a novel open space anxiety test in a single 12
min session. The ...test is based on exposure of mice to an unfamiliar elevated platform which is extended on two opposite sides with steep slopes presented downward or upward. In the first experiment, the behavior of mice was examined on the elevated platform at two different heights (75 and 100
cm) with downward slopes. In the second experiment, we examined the behavior of mice on the platform at the lowest height (75
cm) but with upward slopes which lead to a stand. In the third experiment, we examined the behavior of Balb/c mice on the platform at the lowest height (75
cm) with downward slopes, and a hub enclosure providing a protected space located in the centre of the platform. The least anxious strain of mice was expected to take risks and cross onto the slopes (experiments 1 and 3) and onto the stands (experiment 2). The results of experiment 1 show that Balb/c mice did not cross onto the slope, and CD-1 mice made more crossings into and spent more time on the slopes than c57 mice. The increase in the heights of the platform reduced the number of crossings on the platform in all three strains of mice, and decreased the time spent on the platform before first entry onto a slope in c57 and in CD-1 mice. It also decreased the number of entries and duration of entries onto the slopes in CD-1 mice. In experiment 2, Balb/c mice did cross onto the upward slopes but significantly less than c57 and CD-1 mice but they did not cross onto the stands attached to the end of the slopes. CD-1 mice made more entries onto and spent more time on the stands than c57 mice. In the third experiment, Balb/c and c57 mice spent most of their time inside a protective space (cylinder) placed in the centre of the platform demonstrating strong avoidance responses of the outer area of the platform, and only three c57 mice crossed onto the slopes for a very brief duration in one or two entries. In all three experiments, mice entered more frequently and spent more time in the outer areas than in the inner areas of the platform, particularly in the areas adjacent to slopes than in the areas adjacent to a void space. CD-1 mice appears the least anxious taking more risks by venturing onto the slopes and onto the stands while Balb/c appears the most anxious spending a large amount of time in the areas adjacent to the slopes. The different configurations of the test apparatus (experiments 1 and 2) seem to provide different incentives for the drive to explore and escape which may account for differences in anxiety responses whereas the presence of a protective space (experiment 3) appears to encourage avoidance responses.
The Mascarene Aloes are used in the traditional pharmacopoeia against various ailments including cutaneous diseases and as antispasmodics. Scientific evidence to support these claims is non‐existent ...and mainly based on the scientific repute of A. vera. The antioxidant profile of methanolic leaf extracts of A. purpurea Lam., A. tormentorii (Marais) L. E. Newton & G. D. Rowley, A. lomatophylloides Balf. f., A. macra Haw. and A. vera (L.) Burm. f. was studied using the total antioxidant capacity, copper equivalent and superoxide dismutase assays. In vitro cytotoxicity was evaluated on CAD (Cath.‐a‐differentiated) neuronal cells by the methyl tetrazolium assay, and the neuroprotective profile was assessed using hydrogen peroxide‐induced neurotoxicity with the CAD cells. The aloin and vitexin content were determined by high‐performance liquid chromatography with diode‐array detection. A. purpurea had the highest aloin content (546.6 nmol/g), while A. tormentorii had the highest vitexin content (67.3 nmol/g). A. macra (concentration <0.1 mg/mL) elicited a 10% cytotoxicity effect on CAD cells while other Mascarene Aloes were not cytotoxic. This study validates the antioxidant and neuroprotective potential of Mascarene Aloes focusing on their aloin and vitexin content that are also present in other reputed medicinal Aloes.
Background and Purpose
The histamine H4 receptor has a primary role in inflammatory functions, making it an attractive target for the treatment of asthma and refractory inflammation. These ...observations suggested a facilitating action on autoimmune diseases. Here we have assessed the role of H4 receptors in experimental autoimmune encephalomyelitis (EAE) a model of multiple sclerosis (MS).
Experimental Approach
We induced EAE with myelin oligodendrocyte glycoprotein (MOG35–55) in C57BL/6 female mice as a model of MS. The histamine H4 receptor antagonist 5‐chloro‐2‐(4‐methylpiperazin‐1‐yl)carbonyl‐1H‐indole (JNJ7777120) was injected i.p. daily starting at day 10 post‐immunization (D10 p.i.). Disease severity was monitored by clinical and histopathological evaluation of inflammatory cells infiltrating into the spinal cord, anti‐MOG35–55 antibody production, assay of T‐cell proliferation by 3H‐thymidine incorporation, mononucleate cell phenotype by flow cytometry, cytokine production by elisa assay and transcription factor quantification of mRNA expression.
Key Results
Treatment with JNJ7777120 exacerbated EAE, increased inflammation and demyelination in the spinal cord of EAE mice and increased IFN‐γ expression in lymph nodes, whereas it suppressed IL‐4 and IL‐10, and augmented expression of the transcription factors Tbet, FOXP3 and IL‐17 mRNA in lymphocytes. JNJ7777120 did not affect proliferation of anti‐MOG35–55 T‐cells, anti‐MOG35–55 antibody production or mononucleate cell phenotype.
Conclusions and Implications
H4 receptor blockade was detrimental in EAE. Given the interest in the development of H4 receptor antagonists as anti‐inflammatory compounds, it is important to understand the role of H4 receptors in immune diseases to anticipate clinical benefits and also predict possible detrimental effects.
Linked Articles
This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Abstract Familiarity can imply a reduction of fear and anxiety, which may render learning and memory performance insensitive to NMDA receptor antagonism. Our previous study indicates that MK-801 ...(dizocilpine), NMDA antagonist, increased anxiety and prevented the acquisition of a spatial memory task. Here, we examined whether MK-801 will produce anxiety in mice that were familiar with the test environment. Male C57BL/6J mice were exposed, one session a day for 7 days, to a 3D maze, which consisted of nine arms attached to upward inclined bridges radiating from a nonagonal platform. In this maze, high anxiety mice avoid the arms in the first sessions. One group of mice received saline (SAL) while a second group received MK-801 (MKD1), both on day one. A third group received saline in the first 3 sessions, and MK 801 in subsequent sessions (MKD4). Saline and MK-801 (0.1 mg/kg) were administered intraperitoneally 30 min before the test. MKD4 mice demonstrated an increase in bridge and arm visits, and reached arm/bridge entries ratio close to 1 in session 5. SAL mice also crossed frequently onto the arms, and reached a comparable ratio, but this was achieved with a lower number of arm visits. MKD1 mice demonstrated a reduced number of arm visits in each session compared to SAL and MKD4 mice. Dizocilpine produced anxiety in mice treated from day 1 of the test, but not in those treated from day 4. It also impaired habituation in animals familiar with the test environment; it produced sustained non-habituating hyperactivity.
Dendritic cells (DC) are the major antigen-presenting cells and play a key role in adaptive immunity as they are able to activate naive T cells. It was recently described, that the histamine H₄ ...receptor (H4R) is present on human monocyte-derived DC and that chemotaxis and T-helper (Th)1-Th2 polarization is mediated by this receptor. However, the distribution of histamine receptors on murine DC has not been studied yet. The histamine receptor expression on murine bone marrow (BM)-derived DC and effects of histamine and H4R agonism on DC migration through skin were studied. As it was demonstrated in scratching experiments that NMRI mice are more susceptible to H4R-mediated itch than BALB/c mice, DC function of NMRI and BALB/c mice was compared. The mRNA of the H1R, H2R and H4R could be detected in murine BM-derived DC, while mRNA of the H3R was found to be low or undetectable. There were no distinct differences in mRNA expression and in H4R protein level (flow cytometry) between NMRI compared with BALB/c mice indicating, that a higher susceptibility is not associated with a generally higher H4R expression in all cell types. Histamine as well as the H4R agonist clobenpropit induced an enhanced chemotaxis in the skin DC migration assay. The enhanced chemotaxis was blocked by the H4R antagonist JNJ7777120. This finding was confirmed by in vitro migration experiments with BM-derived DC. Referring to DC migration, blocking the H4R on inflammatory cells might be a promising anti-inflammatory, immunomodulatory strategy.
PDF
