title: Neonatal rat microglia derived from different brain regions have distinct activation responses.
abstract: The regional heterogeneity of neuronal phenotypes is a well-known phenomenon. Whether or not glia derived from different brain regions are phenotypically and functionally distinct is less clear. Here, we show that microglia, the resident immune cells of the brain, display region-specific responses for activating agents including glutamate (GLU), lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP). Primary microglial cultures were prepared from brainstem (Brs), cortex (Ctx), hippocampus (Hip), striatum (Str) and thalamus (Thl) of 1-day-old rats and were shown to upregulate the release of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) in a region- and activator-specific manner. With respect to ATP specifically, ATP-induced changes in microglial tumor necrosis factor-α (TNF-α) release, GLU uptake and purinergic receptor expression were also regionally different. When co-cultured with hypoxia (Hyp)-injured neurons, ATP-stimulated microglia from different regions induced different levels of neurotoxicity. These region-specific responses could be altered by pre-conditioning the microglia in a different neurochemical milieu, with taurine (TAU) being one of the key molecules involved. Together, our results demonstrate that microglia display a regional heterogeneity when activated, and this heterogeneity likely arises from differences in the environment surrounding the microglia. These findings present an additional mechanism that may help to explain the regional selectiveness of various brain pathologies.
authors.affiliation: Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Aaron Y
authors.initials: AY
authors.lastname: Lai
authors.forename: Kamaldeep S
authors.initials: KS
authors.lastname: Dhami
authors.forename: Comfort D
authors.initials: CD
authors.lastname: Dibal
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Todd
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; C489787:MAP2 protein, rat; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha; D003561:Cytarabine; D009569:Nitric Oxide; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; C004479:pimagedine