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The mu-opioid receptor (OPRM1) is the principal receptor target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli and to opiate drugs that are attributed to genetic variations in OPRM1. In searching for new functional variants, we employed comparative genome analysis and(More)
The interplay between innate and adaptive immunity is important in multiple sclerosis (MS). The inflammasome complex, which activates caspase-1 to process pro-IL-1beta and pro-IL-18, is rapidly emerging as a pivotal regulator of innate immunity, with nucleotide-binding domain, leucine-rich repeat containing protein family, pyrin domain containing 3 (NLRP3)(More)
Remyelination in multiple sclerosis (MS) is often incomplete. In experimental models, oligodendrocyte progenitor cells (OPCs) rather than previously myelinating oligodendrocytes (OLs) are responsible for remyelination. This study compares the relative susceptibility of adult human OPCs and mature OLs to injury in actively demyelinating MS lesions and under(More)
FTY720 (fingolimod, Gilenya™) is a daily oral therapy for multiple sclerosis that readily accesses the central nervous system (CNS). FTY720 is a structural analog to the sphingolipid sphingosine-1-phosphate (S1P) and is a cognate ligand for the S1P G-protein coupled receptors (S1PR). Studies in experimental autoimmune encephalomyelitis using mice with(More)
BACKGROUND Opioids are the most widely used analgesics for the treatment of clinical pain. They produce their therapeutic effects by binding to mu-opioid receptors (MORs), which are 7 transmembrane domain (7TM) G-protein-coupled receptors (GPCRs), and inhibiting cellular activity. However, the analgesic efficacy of opioids is compromised by side-effects(More)
Subject recruitment. One hundred ninety six (196) healthy European American pain-free females with an age range of 18 to 34 years were genotyped and phenotyped. Demographic characteristics of the cohort at the time of recruitment have been previously described (1-3). This study was nested within a larger prospective study conducted at the University of(More)
Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain during the postnatal period of peak synapse formation. Here we demonstrate a synaptogenic function of netrin-1 in rat and mouse cortical neurons and investigate the underlying(More)
Multiple sclerosis (MS) is an organ-specific autoimmune disease resulting in demyelinating plaques throughout the central nervous system. In MS, the exact role of microglia remains unknown. On one hand, they can present antigens, skew T cell responses, and upregulate the expression of pro-inflammatory molecules. On the other hand, microglia may express(More)
Mu-opioid receptor (MOR) belongs to a family of heptahelical G-protein-coupled receptors (GPCRs). Studies in humans and rodents demonstrated that the OPRM1 gene coding for MOR undergoes extensive alternative splicing afforded by the genetic complexity of OPRM1. Evidence from rodent studies also demonstrates an important role of these alternatively spliced(More)
OBJECTIVE Remyelination in multiple sclerosis has been attributed to the presence of oligodendrocyte progenitor cells (OPCs) in brain parenchyma. However, the precise identity of these progenitors is poorly defined. Here, we characterized populations of OPCs in the adult human brain and examined their myelination capacity and profile of miRNAs. Comparisons(More)