Microglial phenotypes in Parkinson's disease and animal models of the disease. (August 2017)

• Record Type: Journal Article
• Authors: Joers, Valerie; Tansey, Malú G.; Mulas, Giovanna; Carta, Anna R.
• Is Part Of: Progress in neurobiology. Volume 155(2017:Aug.)
• Page Start: 57
• Page End: 75
• Publication Date: 2017-08
• Subjects: BBB blood-brain barrier -- CSF cerebral spinal fluid -- COX1 cyclo-oxygenase 1 -- COX2 cyclo-oxygenase 2 -- CRP C reactive protein -- DA dopamine -- EGF Epidermal growth factor -- FACIT functional assessment of chronic illness therapy -- FcγRII Fc gamma receptor II -- HADS hospital anxiety and depression scale -- IFN-γ interferon-gamma -- IL-1 βinterleukin-1 beta -- IL-6 interleukin-6 -- IL-12 interleukin-12 -- IP-10 interferon gamma-induced protein-10 -- LRRK2 leucine-rich repeat kinase 2 -- LPS lipopolysaccharide -- MHC-II major histocompatibility complex-II -- MCP-1 monocyte chemotactic protein-1 -- MIP-1β macrophage inflammatory protein-1β -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- NFκB nuclear factor kappa beta -- NT-proCNP N-terminal Pro-C-type natriuretic peptide -- PET positron emission tomography -- RNF11 Ring Finger Protein 11 -- SN substantia nigra -- TGF-β transforming growth factor β -- TNF tumor necrosis factor -- TLR toll-like receptor -- 6-OHDA 6-hydroxydopamine; Microglia -- Neurodegeneration -- Neuroinflammation -- Parkinson's -- Immune -- Neuroprotection; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2016.04.006
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: Microglia exist in a heterogenous population and their phenotypes are not permanently polarized into two categories. Neuroinflammation and microglia activation are considered neuropathological hallmarks, however their precise role in relation to disease progression is not clear. Animal models have provided insights on dynamic changes of microglia phenotypes in relation to disease progression especially prior to the development of motor deficits. Microglial phenotypes in the aging brain become further altered in PD giving rise to a prevalence of pro-inflammatory microglia, which likely contribute to progressive neuronal loss. Malfunction at multiple steps of NFκB signaling that may have a causal interrelationship with pathological microglia activation in animal models of PD. Abstract: Over the last decade the important concept has emerged that microglia, similar to other tissue macrophages, assume different phenotypes and serve several effector functions, generating the theory that activated microglia can be organized by their pro-inflammatory or anti-inflammatory and repairing functions. Importantly, microglia exist in a heterogenous population and their phenotypes are not permanently polarized into two categories; they exist along a continuum where they acquire different profiles based on their local environment. In Parkinson's disease (PD), neuroinflammation and microglia activation are considered neuropathological hallmarks, however their precise role in relation to disease progression is not clear, yet represent a critical challenge in the search of disease-modifying strategies. This review will critically address current knowledge on the activation states of microglia as well as microglial phenotypes found in PD and in animal models of PD, focusing on the expression of surface molecules as well as pro-inflammatory and anti-inflammatory cytokine production during the disease process. While human studies have reported an elevation of both pro- or anti-inflammatory markers in the serum and CSF of PD patients, animal models have provided insights on dynamic changes of microglia phenotypes in relation to disease progression especially prior to the development of motor deficits. We also review recent evidence of malfunction at multiple steps of NFκB signaling that may have a causal interrelationship with pathological microglia activation in animal models of PD. Finally, we discuss the immune-modifying strategies that have been explored regarding mechanisms of chronic microglial activation.