Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions

BACKGROUND: In many neuroinflammatory diseases, dendritic cells (DCs) accumulate in several compartments of the central nervous system (CNS), including the cerebrospinal fluid (CSF). Myeloid DCs invading the inflamed CNS are thus thought to play a major role in the initiation and perpetuation of CNS-targeted autoimmune responses. We previously reported that, in normal rats, DCs injected intra-CSF migrated outside the CNS and reached the B-cell zone of cervical lymph nodes. However, there is yet no information on the migratory behavior of CSF-circulating DCs under neuroinflammatory conditions. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we performed in vivo transfer experiments in rats suffering from experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. EAE or control rats were injected intra-CSF with bone marrow-derived myeloid DCs labeled with the fluorescent marker carboxyfluorescein diacetate succinimidyl ester (CFSE). In parallel experiments, fluorescent microspheres were injected intra-CSF to EAE rats in order to track endogenous antigen-presenting cells (APCs). Animals were then sacrificed on day 1 or 8 post-injection and their brain and peripheral lymph nodes were assessed for the presence of microspheres(+) APCs or CFSE(+) DCs by immunohistology and/or FACS analysis. Data showed that in EAE rats, DCs injected intra-CSF substantially infiltrated several compartments of the inflamed CNS, including the periventricular demyelinating lesions. We also found that in EAE rats, as compared to controls, a larger number of intra-CSF injected DCs reached the cervical lymph nodes. This migratory behavior was accompanied by an accentuation of EAE clinical signs and an increased systemic antibody response against myelin oligodendrocyte glycoprotein, a major immunogenic myelin antigen. CONCLUSIONS/SIGNIFICANCE: Altogether, these results indicate that CSF-circulating DCs are able to both survey the inflamed brain and to reach the cervical lymph nodes. In EAE and maybe multiple sclerosis, CSF-circulating DCs may thus support the immune responses that develop within and outside the inflamed CNS

Considering the Definition of Addiction

The definition of addiction is explored. Elements of addiction derived from a literature search that uncovered 52 studies include: (a) engagement in the behavior to achieve appetitive effects, (b) preoccupation with the behavior, (c) temporary satiation, (d) loss of control, and (e) suffering negative consequences. Differences from compulsions are suggested. While there is some debate on what is intended by the elements of addictive behavior, we conclude that these five constituents provide a reasonable understanding of what is intended by the concept. Conceptual challenges for future research are mentioned

A Framework for the Specificity of Addictions

Research over the last two decades suggests that a wide range of substance and behavioral addictions may serve similar functions. Yet, co-occurrence of addictions has only been reported among a minority of addicts. “Addiction specificity” pertains to a phenomenon in which one pattern of addictive behaviors may be acquired whereas another is not. This paper presents the PACE model as a framework which might help explain addiction specificity. Pragmatics, attraction, communication, and expectation (PACE) variables are described, which may help give some direction to future research needs in this arena

Immune Modulating Peptides for the Treatment and Suppression of Multiple Sclerosis

Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system recognizes proteins of the myelin sheath as antigenic, thus initiating an inflammatory reaction in the central nervous system. This leads to demyelination of the axons, breakdown of the blood-brain barrier, and lesion formation. Current therapies for the treatment of MS are generally non-specific and weaken the global immune system, thus making the individual susceptible to opportunistic infections. Antigenic peptides and their derivatives are becoming more prevalent for investigation as therapeutic agents for MS because they possess immune-specific characteristics. In addition, other peptides that target vital components of the inflammatory immune response have also been developed. Therefore, the objectives of this review are to (a) summarize the immunological basis for the development of MS, (b) discuss specific and non-specific peptides tested in EAE and in humans, and (c) briefly address some problems and potential solutions with these novel therapies

Cover and contents : “Proceedings of the 11th CEReS Symposium on Enviromental Remote Sensing” February 23, 2009

2009年2月23日（月） 於 千葉大学けやき会