Abstract
Microglia are important cells in the brain that can acquire different morphological and functional phenotypes dependent on the local situation they encounter. Knowledge on the region-specific gene signature of microglia may hold valuable clues for microglial functioning in health and disease, e.g., Parkinson’s disease (PD) in which microglial phenotypes differ between affected brain regions. Therefore, we here investigated whether regional differences exist in gene expression profiles of microglia that are isolated from healthy rat brain regions relevant for PD. We used an optimized isolation protocol based on a rapid isolation of microglia from discrete rat gray matter regions using density gradients and fluorescent-activated cell sorting. Application of the present protocol followed by gene expression analysis enabled us to identify subtle differences in region-specific microglial expression profiles and show that the genetic profile of microglia already differs between different brain regions when studied under control conditions. As such, these novel findings imply that brain region-specific microglial gene expression profiles exist that may contribute to the region-specific differences in microglia responsivity during disease conditions, such as seen in, e.g., PD.
Highlights
Microglia are the primary, innate immune cells of the central nervous system (CNS) responsible for safeguarding and maintenance of brain homeostasis
Prior studies have suggested that microglial activation is largely detrimental in the context of homeostatic brain disturbances, it is well accepted that microglia can benefit CNS function and provide neuroprotection, shape neuronal circuits and promote axonal regeneration (Ekdahl et al, 2003; Walter and Neumann, 2009; Welser et al, 2010; Czeh et al, 2011; Wake et al, 2013)
After sorting of the microglial cells, their amount ranged from 1.1 × microglial cells in the substantia nigra (SN) to 1.2 × microglial cells in the olfactory bulb (OB) (Table 2)
Summary
Innate immune cells of the central nervous system (CNS) responsible for safeguarding and maintenance of brain homeostasis. By constantly surveying their microenvironment, microglia can quickly respond to a disturbed homeostasis caused, by e.g., pathogens or injury. Under such conditions, microglia undergo typical morphological and functional alterations and become engaged in processes like phagocytosis, cytokine production, antigen presentation and/or cell proliferation (Nimmerjahn et al, 2005; Hanisch and Kettenmann, 2007; Kettenmann et al, 2011; Doorn et al, 2014a). Previous views on microglia as a rather uniform cell population present throughout the brain, have been replaced by the concept that these cells can acquire specific phenotypes depending on their region-specific environment (Lucin and Wyss-Coray, 2009; Ransohoff and Perry, 2009; Olah et al, 2011)
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