Brain-resident microglia predominate over infiltrating myeloid cells in activation, phagocytosis and interaction with T-lymphocytes in the MPTP mouse model of Parkinson disease

Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model

“…Ex vivo labeling of the CD163ϩ macrophages allowed us to follow them in vivo and confirmed their infiltration from the periphery to the brain parenchyma. This is consistent with previous reports documenting infiltration of macrophages, but also T cells, in different neurodegenerative models including PD (Kurkowska-Jastrzebska et al, 1999;Kokovay and Cunningham, 2005;Simard et al, 2006;Rodriguez et al, 2007;Depboylu et al, 2012;Theodore and Maragos, 2015). These infiltrated macrophages may acquire later microglia characteristics (Simard and Rivest, 2004).…”

“…It has been proposed that the immune system plays an active part in the symptoms and progression of PD (Doorn et al, 2012;Blandini, 2013). Supporting this, epidemiological studies show that the use of nonaspirin NSAIDs decreases the risk of developing PD (Rees et al, 2011) and genetic studies described a significant association between polymorphisms in the HLA gene loci and the risk for late-onset PD (Hamza et al, 2010;International Parkinson Disease Genomics Consortium, 2011).…”

“…We have shown previously that both in vitro and in vivo, anti-CD163-Dexa-conjugate attenuated the LPS-induced inflammatory response in rats (Graversen et al, 2012). CD163 is a hemoglobin scavenger receptor (Kristiansen et al, 2001) expressed in monocytes/macrophages that has been involved in different inflammatory diseases Dultz et al, 2016;Liu et al, 2015). In the brain, CD163 is expressed in perivascular macrophages (PVMs) but not in microglia, so it constitutes a potential marker for infiltrated peripheral immune cells in the brain parenchyma (Polfliet et al, 2006).…”

Persistent phagocytic characteristics of microglia in the substantia nigra of long-term Parkinsonian macaques

“…However, the specific role of microglia during this persistent stage is still under scrutiny. We and others have recently reported that in an experimental mouse model of PD in which Parkinsonism was induced by MPTP, microglial motility leads to the formation of complex body-to-body contacts between microglia and dopaminergic neurons that result in the phagocytosis of neuronal cell bodies in the areas of degeneration (Barcia et al, 2012;Depboylu et al, 2012). In mice, interactions between microglia and neurons are transient and precede the elimination of damaged dopaminergic neurons (Barcia et al, 2012).…”

Neurodegeneration and Neuroglia: Emphasis on Astroglia in Alzheimer’s Disease

“…In recent years, neuroinflammatory component begun to be considered in the context of PD and there are indications of specific role for activated microglia in causing the death of dopaminergic neurons (Depboylu et al 2012), although there are also data showing that the activation of microglia follows the death of neurons, rather than causing it (Henry et al 2009). Pharmacological inhibition of microglial activation was found to be neuroprotective against 6-hydroxydopamine (6-OHDA) neurotoxicity (Lazzarini et al 2013), the treatment with 6-OHDA being employed to generate one of the most common animal model of PD.…”