Dual role of microglia in health and disease: pushing the balance toward repair.

摘要: Microglial cells have been traditionally regarded as the rowdy foot soldiers of Central Nervous System (CNS), always on edge causing massive destruction when provoked. Nevertheless, microglia are responsible and/or strongly contribute to maintenance CNS homeostasis, immune surveillance and synaptic plasticity. Until now, it was believed these complex processes depended two polarizing stimuli received by microglia: “bad” ones leading a classical pro-inflammatory response (M1), “good” typical anti-inflammatory profile (M2). However, under M1 M2 conditions, can differentiate into different population subsets develop specific patterns activity. Gertig Hanisch (2014) extensively review heterogeneity responses discuss how impacts cytokine production, clearance tissue debris, antigen presentation or ability sense neurotransmitters. The challenge will be development tools that allow us select subpopulation interest modulate its specifically an optimal therapeutic effect. Microglia classically addressed resident macrophages CNS. In sense, committed removal foreign/infectious particles cellular components maintain healthy brain parenchyma. Nau et al. distinguish pathways which increase phagocytosis intracellular elimination pathogens albeit with outcomes neuronal survival. Stimulation one several toll-like receptors nucleotide-binding oligomerization domain-containing protein 2 leads release products damage. Conversely, authors report activation palmitoylethanolamide increases without mediators. discovery molecules eliminate damaging surrounding likely strengthen resist infection. On latter phagocytic function microglia, Gitik show paxillin cofilin promotes degenerated myelin in SIRP-alpha knocked-down positive correlation between phagocytosis. Myelin breakdown occurs following traumatic axonal injury neurodegenerative disorders such multiple sclerosis. Understanding mechanisms underlying necessary strategies promote remyelination more efficiently while preserving nearby intact tissue. This study further emphasizes importance studying nature their interactions other cell types at stages disease progression order maximize overall recovery Chronic also amyotrophic lateral sclerosis (ALS), most aggressive form adult motor neuron degeneration. Brites Vaz intricate crosstalk neurons glial cells, including ALS onset progression. early stage beneficial effect overly activated later become neurotoxic. neuron-microglia selection adequate model contribution this dynamics warrants attention from Neiva (2014). group discusses important biochemical physiological differences immortalized lines primary alert possible pitfalls using artificial culture systems. note, suggest supplementation microglial media fractalkine induces vivo-like morphology behavior compared vitro models. Although proposed requires additional characterization is aware strategy we choose validate detrimental properties. An emerging target for anti-neuroinflammatory histamine, mainly known role peripheral inflammatory mediator. Rocha current literature histamine modulation activity but present new data secretome histamine-stimulated dopaminergic death. By examining effects antihistamines survival, unveil perspectives platforms Parkinson's disease. changes not only pathological context aging brain. To better understand mechanisms, Caldeira propose reactive aged microglia. study, 16 days evidence morphological reduced functional corresponding irresponsive/senescent cells. life expectancy age-related diseases highlights developing control recover Both lead loss extents. approach delay halt death replacement dead/dying stimulate neurogenesis. neurogenic niche has increasingly addressed. Marshall regional (neurogenic niches vs. cerebral cortex) affect proliferative Authors conclude possess intrinsic spatially-restricted characteristics them distinct populations independently environment. distinction allows isolated efficient promoting interact shape mature neurons. Cristovao comment novel pre-synaptic differentiation means formation aberrant synapse occurring neurodevelopment disorders. cause significant density marker synapsin I, observed presence non-primed axons. dissecting maternal infection during pregnancy they may impact fetal formation. research topic, researchers presented work views molecular developed disease, remodeling aging. We expect herein advance our understanding microglia-mediated toward survival regeneration therefore approaches repair diseased injured