Cytokines and CNS development.

Division of Biology, California Institute of Technology, 1200 East California Boulevard M/C 216-76, Pasadena, CA 91125, USA.
Neuron (Impact Factor: 15.98). 10/2009; 64(1):61-78. DOI: 10.1016/j.neuron.2009.09.002
Source: PubMed

ABSTRACT Cytokines are pleotrophic proteins that coordinate the host response to infection as well as mediate normal, ongoing signaling between cells of nonimmune tissues, including the nervous system. As a consequence of this dual role, cytokines induced in response to maternal infection or prenatal hypoxia can profoundly impact fetal neurodevelopment. The neurodevelopmental roles of individual cytokine signaling pathways are being elucidated through gain- and loss-of-function studies in cell culture and model organisms. We review this work with a particular emphasis on studies where cytokines, their receptors, or components of their signaling pathways have been altered in vivo. The extensive and diverse requirements for properly regulated cytokine signaling during normal nervous system development revealed by these studies sets the foundation for ongoing and future work aimed at understanding how cytokines induced normally and pathologically during critical stages of fetal development alter nervous system function and behavior later in life.


Available from: Paul H Patterson, Apr 18, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The immunomodulatory cytokine interleukin-33 (IL-33) is a member of the IL-1 cytokine family. Its high level of expression in the central nervous system (CNS) suggests it is likely to play an important role in CNS function. Current research evidence indicates it is involved in the development of several neurological autoimmune. diseases, including multiple sclerosis (MS).However, the function of IL-33 in CNS homeostasis under healthy physiological conditions is yet to be clarified. This study therefore aims to further understand the exact function and the underlying mechanism of IL-33 in the CNS through investigating: 1) the regional expression of IL-33 and its receptor ST2 in brain tissues of naïve (healthy) and diseased mice; to compare the expression of IL-33 and ST2 receptors in CNS under healthy and diseased condition and 2) the expression of IL-33 and ST2 in the hippocampal culture cells and the function of IL-33 in the brain under healthy conditions.
    01/2015, Degree: MRes in Biomedical Science, Supervisor: Dr.Hui Rong Jiang and Dr.Trevor Bushell
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Increasing epidemiological and experimental evidence implicates gestational infections as one important factor involved in the pathogenesis of several neuropsychiatric disorders. Corresponding preclinical model systems based upon maternal immune activation (MIA) by treatment of the pregnant female have been developed. These MIA animal model systems have been successfully used in basic and translational research approaches, contributing to the investigation of the underlying pathophysiological mechanisms at the molecular, cellular and behavioural levels. The present article focusses on the application of a specific MIA rodent paradigm, based upon treatment of the gestating dam with the viral mimic polyinosinic-poly cytidilic acid (Poly(I:C)), a synthetic analog of double-stranded RNA (dsRNA) which activates the Toll-like receptor 3 (TLR3) pathway. Important advantages and constraints of this animal model will be discussed, specifically in light of gestational infection as one vulnerability factor contributing to the complex aetiology of mood and psychotic disorders, which are likely the result of intricate multi-level gene x environment interactions. Improving our currently incomplete understanding of the molecular pathomechanistic principles underlying these disorders is a prerequisite for the development of alternative therapeutic approaches which are critically needed in light of the important drawbacks and limitations of currently available pharmacological treatment options regarding efficacy and side effects. The particular relevance of the Poly(I:C) MIA model for the discovery of novel drug targets for symptomatic and preventive therapeutic strategies in mood and psychotic disorders is highlighted in this review article.
    Pharmacology [?] Therapeutics 01/2015; 116. DOI:10.1016/j.pharmthera.2015.01.001 · 7.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Longitudinal epidemiological studies with birth cohorts have shown that physical aggression in humans does not appear suddenly in adolescence as commonly thought. In fact, physically aggressive behaviour is observed as early as 12 months after birth, its frequency peaks around 2-4 years of age and decreases in frequency until early adulthood. However, a minority of children (3-7%) maintain a high frequency of physical aggression from childhood to adolescence and develop serious social adjustment problems during adulthood. Genetic factors and early social experiences, as well as their interaction, have been shown to play an important role in the development of chronic aggressive behaviour. However, the biological mechanisms underlying these associations are just beginning to be uncovered. Recent evidence suggests that epigenetic mechanisms are responsive to adverse environments and could be involved in the development of chronic aggression. Using both gene candidate and genomic approaches, recent studies have identified epigenetic marks, such as DNA methylation alterations in genes involved in the stress response and the serotonin and immune systems to be partly responsible for the long-lasting effects of early adversity. Further longitudinal studies with biological, environmental and behavioural assessments from birth onwards are needed to elucidate the sequence of events that leads to these long-lasting epigenetic marks associated with early adversity and aggression. © 2015. Published by The Company of Biologists Ltd.
    Journal of Experimental Biology 01/2015; 218(Pt 1):123-133. DOI:10.1242/jeb.111401 · 3.00 Impact Factor

Similar Publications