Neuroinflammation contributes to many neurologic disorders including Alzheimer’s disease, multiple sclerosis, and stroke. Microglia is brain resident myeloid cells and have emerged as a key driver of the neuroinflammatory responses. MicroRNAs (miRNAs) provide a novel layer of gene regulation and play a critical role in regulating the inflammatory response of peripheral macrophages. However, little is known about the miRNA in inflammatory activation of microglia. To elucidate the role that miRNAs have on microglial phenotypes under classical (M1) or alternative (M2) activation under lipopolysaccharide (‘M1’-skewing) and interleukin-4 (‘M2a’-skewing) stimulation conditions, we performed microarray expression profiling and bioinformatics analysis of both mRNA and miRNA using primary cultured murine microglia. miR-689, miR-124, and miR-155 were the most strongly associated miRNAs predicted to mediate pro-inflammatory pathways and M1-like activation phenotype. miR-155, the most strongly up-regulated miRNA, regulates the signal transducer and activator of transcription 3 signaling pathway enabling the late phase response to M1-skewing stimulation. Reduced expression in miR-689 and miR-124 are associated with dis-inhibition of many canonical inflammatory pathways. miR-124, miR-711, miR-145 are the strongly associated miRNAs predicted to mediate anti-inflammatory pathways and M2-like activation phenotype. Reductions in miR-711 and miR-124 may regulate inflammatory signaling pathways and peroxisome proliferator-activated receptor-gamma pathway. miR-145 potentially regulate peripheral monocyte/macrophage differentiation and faciliate the M2-skewing phenotype. Overall, through combined miRNA and mRNA expression profiling and bioinformatics analysis we have identified six miRNAs and their putative roles in M1 and M2-skewing of microglial activation through different signaling pathways.

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Peripheral and CNS inflammation leads to aberrations in developmental and

Systemic lupus erythematosus (SLE) is a chronic, multiorgan, systemic autoimmune disease that is more common in women than men and is typically diagnosed during reproductive age, necessitating sex-specific considerations in care. In women there is no substantive evidence to suggest that SLE reduces fertility, but subfertility may occur as a result of active disease, immunosuppressive drugs, and age-related declines in fertility related to delays in childbearing. Although pregnancy outcomes have improved, SLE still poses risks in pregnancy that contribute to poorer maternal and fetal outcomes. Cyclophosphamide, an important agent for the treatment of severe or life-threatening lupus, may adversely affect fertility, particularly with increases in dose and patient age. Fertility

The emerging field of neuroimmune pharmacology (NIP) is the confluence of three distinct disciplines: neuroscience, immunology, and pharmacology (Gendelman and Ikezu 2008). NIP was born from the realization that inflammation within the central nervous system (CNS) plays a crucial role in many neurological pathologies and as such offers a rich array of novel pharmacological targets as potential therapeutics. As this field is likely to have a major impact in medical science, educating future physicians on this area will help increase awareness and may potentially inspire them to pursue careers in the field of NIP. However, a key challenge for medical educators, is how best to incorporate new material on emerging fields, such as NIP, into the medical school curriculum, specifically in the context of a medical neuroscience course. We propose the addition of two 50-min lectures plus an additional optional 2-h lab module to the standard first year medical neuroscience class curriculum. Lecture 1 will focus on how the CNS and the immune system inter-communicate with one another with emphasis on neuroanatomical features and chemical signal transduction between the two systems. Lecture 2 provides an introduction to inflammation in the CNS and provides a series of clinical correlates to describe how CNS inflammation contributes to the disease process. The lab module provides detailed visual examples of how CNS inflammation influences disease processes and provides two examples of how application of an immunomodulatory pharmacological agent can modify disease processes.