Age-dependent impairment in learning and memory functions occurs in many animal species, including humans. Although cell death contributes to age-related cognitive impairment in pathological forms of aging, learning and memory deficiencies develop with age even without substantial cell death. The molecular and cellular basis of this biological aging process is not well understood but seems to involve a decline in the aging brain's capacity for experience-dependent plasticity. To aid in resolving this issue, we used a simple snail appetitive classical conditioning paradigm in which the underlying molecular, cellular, and neural network functions can be directly linked to age-associated learning and memory performance (i.e., the Lymnaea stagnalis feeding system). Our results indicate that age does not affect the acquisition of appetitive memory but that retention and/or consolidation of long-term memory become progressively impaired with advancing age. The latter phenomenon correlates with declining electrophysiological excitability in key neurons controlling the feeding behavior. Together, these results present the Lymnaea feeding system as a powerful paradigm for investigations of cellular and molecular foundations of biological aging in the brain.

Contact sensitivity (CS) is one of the primary in vivo models of T cell-mediated inflammation. The presence of CS-initiating CD4 T lymphocytes at the time of challenge is essential for transfer and full development of the late phase CS inflammatory response. From this observation investigators have speculated that early recruitment of CD4 T cells to the site of challenge must occur. Moreover, there must be rapid synthesis/release and disappearance of an important mediator during the first hours after hapten challenge. Using spinning disk confocal microscopy, we observed the very early effector events of the immune response. Simultaneous, real-time visualization of predominant neutrophil and extremely rare CD4 T cell trafficking in the challenged skin vasculature was noted (one rolling CD4 T cell for every 10–18 rolling and adherent neutrophils). We demonstrate that neutrophil adhesion during the early CS response was reduced in C5a receptor-deficient (C5aR−/−) mice or leukotriene B4 receptor antagonist-treated mice, whereas CD4 T cell recruitment was only inhibited in C5aR−/− mice. In line with these observations, leukocyte infiltration and the associated tissue damage were significantly reduced in C5aR−/− mice but not in leukotriene B4 receptor antagonist-treated wild-type mice 24 h after challenge. C5a receptor expression on T cells and not on tissue resident cells was important for the development of a CS response. Thus, by using spinning disk confocal microscopy we visualized the early events of an adaptive immune response and identified the rare but essential recruitment of CD4 T cells via the complement pathway.

The role that mast cells play during contact hypersensitivity (CS) response is unclear because some studies have shown that mast cell-deficient mice have relatively intact CS responses whereas others have shown opposing results. Mast cells secrete a wide range of immunomodulatory mediators and can potentially influence the type of immune response generated in the skin during CS. Therefore, we examined the type of microenvironment generated during CS in both W/Wv mast cell-deficient and wild-type mice in response to different immunizing doses of hapten (oxazolone). The CS response elicited after low-dose oxazolone was significantly diminished in W/Wv mice compared with wild-type mice. Unexpectedly, the CS response elicited in W/Wv mice immunized with high-dose oxazolone was more severe compared with wild-type mice. In addition, after immunization with high-dose oxazolone, the granulocyte infiltrate in W/Wv mice was increased by twofold compared with wild-type mice. A shift in the cytokine milieu toward the expression of type-1 cytokines as well as a significant increase in the local adhesion of neutrophils and CD4 T cells in the microvasculature of the skin was observed after hapten challenge in W/Wv mice immunized with high-dose oxazolone compared with wild-type mice. These results suggest that mast cells can act as regulators and inducers of the inflammatory response depending on immunizing stimulus strength.

478Although there is evidence of an influence of estrogen on the dopaminergic system, 1-2 little is known about the exact mechanisms of action of estrogens on basal ganglia circuitry and their influence on movement disorders.Epidemiological studies have found some clinical genderrelated differences in patients with Parkinson's disease (PD), such as a slightly greater prevalence of PD in men, 3 higher motor scores (i.e., more severe disease) in men using the Unified Parkinson Disease Rating Scale and greater prevalence of levodopa-induced dyskinesia in women.4 Some studies have assessed the possible benefit of hormone replacement therapy in post-menopausal women with PD. [5][6] Moreover, estrogens have been demonstrated to be neuroprotective in both in vitro and in vivo studies.7-8 These findings suggest possible dopaminergic and neuroprotective effects of estrogens. ABSTRACT:Background: A possible influence of estrogens on the dopaminergic system has been hypothesized and investigated by several studies, and fluctuations in motor symptoms related to the menstrual cycle have been reported in some movement disorders patients. We designed a survey to quantify how frequently female patients with various movement disorders are affected by this phenomenon and its impact on symptom severity. Methods: A questionnaire was sent to 104 women between 18-and 60-years-old diagnosed with movement disorders and regularly followed at our centre. Results: From a total of 65 subjects who completed the questionnaire, 54 women reported the onset of their movement disorders before menopause. Twenty of them (37%) experienced changes in their movement disorders during the menstrual cycle. In particular, there was a significant worsening of symptom severity before (p=0.0005) and during menses (p=0.0004). Conclusions: The possible role of such changes should be taken into account when evaluating the efficacy of various therapeutic interventions in movement disorder patients. RÉSUMÉ:Enquête sur l'impact du cycle menstruel sur la sévérité des troubles du mouvement. Contexte : Plusieurs études ont évalué l'hypothèse selon laquelle les oestrogènes auraient une influence sur le système dopaminergique. Des fluctuations des symptômes moteurs reliées au cycle menstruel ont été rapportées chez certaines patientes atteintes de troubles du mouvement. Nous avons procédé à une enquête pour quantifier la fréquence de ce phénomène chez des patientes atteintes de différents troubles du mouvement et son impact sur la sévérité des symptômes. Méthodes : Un questionnaire a été envoyé à 104 femmes âgées de 18 à 60 ans chez qui un diagnostic de trouble du mouvement avait été posé et qui avaient été suivies régulièrement dans notre centre. Résultats : Cinquante-quatre des 65 femmes qui ont complété le questionnaire ont rapporté que leur trouble du mouvement avait commencé avant la ménopause. Vingt d'entre elles (37%) avaient noté des changements dans leur trouble du mouvement au cours de leur cycle menstruel, notamment une augmentation significative de la sévé...