Altered emotional and motivational processing in the transgenic rat model for Huntington's disease.

Huntington disease (HD) is caused by an expansion of CAG repeat in the Huntingtin gene. Patients demonstrate a triad of motor, cognitive and psychiatric symptoms. A transgenic rat model (tgHD rats) carrying 51 CAG repeats demonstrate progressive striatal degeneration and polyglutamine aggregates in limbic structures. In this model, emotional function has only been investigated through anxiety studies. Our aim was to extend knowledge on emotional and motivational function in symptomatic tgHD rats. We subjected tgHD and wild-type rats to behavioral protocols testing motor, emotional, and motivational abilities. From 11 to 15 months of age, animals were tested in emotional perception of sucrose using taste reactivity, acquisition, extinction, and re-acquisition of discriminative Pavlovian fear conditioning as well as reactivity to changes in reinforcement values in a runway Pavlovian approach task. Motor tests detected the symptomatic status of tgHD animals from 11 months of age. In comparison to wild types, transgenic animals exhibited emotional blunting of hedonic perception for intermediate sucrose concentration. Moreover, we found emotional alterations with better learning and re-acquisition of discriminative fear conditioning due to a higher level of conditioned fear to aversive stimuli, and hyper-reactivity to a negative hedonic shift in reinforcement value interpreted in term of greater frustration. Neuropathological assessment in the same animals showed a selective shrinkage of the central nucleus of the amygdala. Our results showing emotional blunting and hypersensitivity to negative emotional situations in symptomatic tgHD animals extend the face validity of this model regarding neuropsychiatric symptoms as seen in manifest HD patients, and suggest that some of these symptoms may be related to amygdala dysfunction.

Reduced airway inflammation in CD26/DPP4-deficient F344 rats is associated with altered recruitment patterns of regulatory T cells and expression of pulmonary surfactant proteins.

INTRODUCTION: CD26 is highly expressed on lung epithelial cells as well as on immune cells. Ovalbumin (OVA)-induced airway inflammation induces a further increase of CD26 expression. CD26-deficient rat strains exhibit blunted clinical courses in models of experimental asthma. OBJECTIVE: (1) To investigate the involvement of regulatory T cells (Tregs) and the surfactant system in a rat model of genetic CD26 deficiency. (2) To investigate regulatory mechanisms dependent on the endogenous CD26 expression. (3) To investigate the impact of CD26 on surfactant protein (SP)-levels under inflammatory conditions. METHODS: Wild-type and CD26-deficient F344 rats were sensitized to and challenged with OVA. Subsequently, airway inflammation, SP levels as well as surface tension of the bronchoalveolar lavage (BAL) fluid were evaluated. RESULTS: CD26 deficiency led to decreased airway inflammation, e.g. reduced numbers of eosinophils and activated T cells in the BAL. Remarkably, the CD26-deficient rats exhibited a significantly increased influx of FoxP3(+) Tregs into the lungs and increased IL-10-secretion/production by draining lymph node cells in culture experiments. Furthermore, in OVA-challenged CD26-deficient rats, the increase of the expression of the collectins SP-A and SP-D as well as of the surface tension-active SP-B was significantly less pronounced than in the CD26-positive strain. Only in the wild-type rats, functional alterations of the surfactant system, e.g. the increased surface tension were obvious after OVA challenge. CONCLUSION: Reduced airway inflammation in CD26-deficient F344 rats appear to be mediated by differences in the recruitment and activity of Tregs. This altered inflammation is associated with differences in the SP expression as well as function.

Use of oral irrigators as vehicle for the application of antimicrobial agents in chemical plaque control.

The purpose of the present investigation was to study the topographical distribution of plaque formation using chlorhexidine digluconate (CH) as a mouthrinse and in oral irrigators during experimental gingivitis. Forty dental students (aged 22--26) with clean teeth and healthy gingivae abolished oral hygiene for a period of 3 weeks (Löe et al. 1965). During this period the participants were randomly assigned to one of five groups. Group A rinsed daily with 30 ml of a placebo and Group B with 30 ml 0.1% chlorhexidine digluconate. In Groups C and E a fractionated jet irrigator was used for the daily application of 600 ml placebo (C) or 0.05% CH (E); 600 ml of 0.05% CH was also used in a monojet irrigator (Group D). At the start, after 1, 2 and 3 weeks of no oral hygiene and 1 week following reinstituted oral hygiene, plaque was assessed using the Plaque Index (Silness & Löe 1964) and gingival health was scored according to the criteria of the Gingival Index (Löe & Silness 1963). The discoloration of the teeth was determined using a set of color photos. During the experiment all groups reached plaque levels that were significantly different from each other. The highest PlI were seen in the placebo rinsing group (A) following by placebo irrigation (C). Plaque was significantly reduced in the CH groups. However, rinsing group (A) followed by placebo irrigation (C). Plaque was significantly reduced in the CH groups. However, rinsing (B) formed significantly more plaque than using the oral irrigator (D, E). Group E showed the least amount of plaque. In addition, the interproximal PlI were equally low as the buccal and lingual. With CH (B, D, E), gingivitis did not develop except for some interproximals in Group B. A fractionated jet irrigator was more effective for the application of CH than rinsing.