Ciglitazone increases basal cytokine expression in the central nervous system of adult rats

Gelinas, David; Lambermon, Mark H. L.; McLaurin, JoAnne

doi:10.1016/j.brainres.2004.12.003

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…PAP‐1 treatment reduced the level of IL‐1β‐ir detected in AON optic nerve to approximately one‐tenth the level of IL‐1β‐ir detected in normal optic nerve. These results are consistent with published reports that IL‐1β has a high constitutive expression by microglia of the normal CNS (Gélinas et al, 2005) and is up‐regulated and secreted by the activated microglia (Howe et al, 2006), reactive astrocytes (Fernandes et al, 2006), and activated mast cells (Woolley and Tetlow, 2000; Fairweather et al, 2004; Sandler et al, 2007), which are present in MS lesions (Olsson, 1974; Kruger et al, 1990; Wucherpfennig et al, 1992; Benveniste, 1997).…”

Section: Resultssupporting

confidence: 94%

Transient 5‐(4‐phenylbutoxy)psoralen (PAP‐1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles

Stokely

Garg

Bhat³

et al. 2008

J of Neuroscience Research

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Discovery of treatments to protect axonal function of neurons and prevent permanent disability associated with progressive multiple sclerosis (MS) has faced the uphill challenge of assessing relatively small changes in accumulated axon damage within a background environment that is disorganized by CNS inflammation. We hypothesized that transient immunosuppression after initiation of MS-like autoimmune mechanisms would disassociate development of MS-like myelinated axon pathology from development of CNS inflammation in a rat model of autoimmune optic neuritis (AON). A rat model of myelin oligodendrocyte glycoprotein peptide-induced AON was transiently treated (on days 3-7 after antigen exposure) with 5-(4-phenylbutoxy)psoralen (PAP-1), an immunomodulatory drug previously shown specifically to suppress proliferation of effector memory T-cells and immunoglobulin class-switched B-cells. Thirteen days after antigen exposure, optic nerves were harvested for quantitative assessment of 12 MS-associated pathologies using microfluorimetry. With one exception, the immunoreactivities (-ir) for eight markers of MS-like neuroinflammation and immune infiltration were significantly reduced (P < 0.05) by transient PAP-1 treatment, often to levels significantly below those detected in normal control rat optic nerves. With one exception, four immunoreactive markers of MS-like myelinated axon pathology were detected at levels indicating increased axon/myelin pathology compared with vehicle-treated rats with AON (P < 0.05). These data suggest the conclusion that early causative mechanisms in CNS autoimmunity initiate signaling mechanisms that diverge into two separate pathways, one that is strongly associated with inflammatory responses and one that is associated predominantly with disturbed axon-myelin interactions and impaired fast axonal transport.

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Section: Resultssupporting

confidence: 94%

Transient 5‐(4‐phenylbutoxy)psoralen (PAP‐1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles

Stokely

Garg

Bhat³

et al. 2008

J of Neuroscience Research

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“…One study with primary ESCs also found increased IL-6 mRNA after exposure to a range of PPAR-g agonists (18). Ciglitazone increased the expression of TNF-a-induced IL-6 mRNA in human cardiac fibroblasts (30), and troglitazone treatment significantly increased both IL-1b and TNF-a mRNA in the central nervous system of rats (39). Another study with human monocytes found that ciglitazone had no effect on IL-6 mRNA but did increase both IL-1 and TNF-a mRNA (40), and a PPAR-g dependent increase in IL-8 mRNA expression occurred in treated cultured macrophage cells (41).…”

Section: Discussionmentioning

confidence: 88%

Peroxisome proliferating activating receptor gamma–independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones

McKinnon

Bersinger

Mueller

2012

Fertility and Sterility

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“…A glial modulator that has been investigated in this respect is the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, pioglitazone (PIO or Actos). PPARs belong to the nuclear hormone receptor family and are expressed in neurons, oligodendrocytes, astrocytes and microglia within the central nervous system (Gélinas et al, 2005; Moreno et al, 2004; Sarruf et al, 2009; Woods et al, 2003). Interest in PPARγ agonists has grown in many neuroinflammatory disorders due to the expression of PPARγ primarily in microglia and the ability of PPARγ agonists to inhibit the expression of cytokines by monocytes/macrophages and microglia (Kielian and Drew, 2003).…”

Section: Drugs Of Abuse and Glial Cell Activitymentioning

confidence: 99%

Glial and neuroinflammatory targets for treating substance use disorders

Bachtell

Jones

Heinzerling

et al. 2017

Drug and Alcohol Dependence

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Background The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders. Methods Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders. Results Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders. Conclusions The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

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Ciglitazone increases basal cytokine expression in the central nervous system of adult rats

Cited by 13 publications

References 37 publications

Transient 5‐(4‐phenylbutoxy)psoralen (PAP‐1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles

Transient 5‐(4‐phenylbutoxy)psoralen (PAP‐1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles

Peroxisome proliferating activating receptor gamma–independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones

Glial and neuroinflammatory targets for treating substance use disorders

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