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Microglia-Induced Maladaptive Plasticity Can Be Modulated by Neuropeptides In Vivo
Stefano Morara1, Anna Maria Colangelo2, Luciano Provini3
1Neuroscience Institute (CNR), Via Vanvitelli 32, 20129 Milano, Italy ; Department of BIOMETRA, University of Milano, Via Vanvitelli 32, 20129 Milano, Italy.
Abstract:
Microglia-induced maladaptive plasticity is being recognized as a major cause of deleterious self-sustaining pathological processes that occur in neurodegenerative and neuroinflammatory diseases. Microglia, the primary homeostatic guardian of the central nervous system, exert critical functions both during development, in neural circuit reshaping, and during adult life, in the brain physiological and pathological surveillance. This delicate critical role can be disrupted by neural, but also peripheral, noxious stimuli that can prime microglia to become overreactive to a second noxious stimulus or worsen underlying pathological processes. Among regulators of microglia, neuropeptides can play a major role. Their receptors are widely expressed in microglial cells and neuropeptide challenge can potently influence microglial activity in vitro. More relevantly, this regulator activity has been assessed also in vivo, in experimental models of brain diseases. Neuropeptide action in the central nervous system has been associated with beneficial effects in neurodegenerative and neuroinflammatory pathological experimental models. This review describes some of the mechanisms of the microglia maladaptive plasticity in vivo and how neuropeptide activity can represent a useful therapeutical target in a variety of human brain pathologies.
Insights
Microglia drive harmful plasticity in brain diseases. Neuropeptides can regulate microglia, offering a potential therapeutic target for neurodegenerative and neuroinflammatory conditions.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia, the central nervous system's immune cells, maintain brain homeostasis but can contribute to neuroinflammation and neurodegeneration.
- Disruptions from neural or peripheral stimuli can lead to microglial overreactivity and maladaptive plasticity, worsening pathological processes.
- Neuropeptides are emerging as key regulators of microglial function.
Purpose of the Study:
- To review the mechanisms of microglia-induced maladaptive plasticity in vivo.
- To explore the role of neuropeptides in modulating microglial activity.
- To discuss the therapeutic potential of targeting neuropeptide pathways for brain pathologies.
Main Methods:
- Literature review of in vitro and in vivo studies on microglia and neuropeptides.
- Analysis of experimental models of neurodegenerative and neuroinflammatory diseases.
- Examination of neuropeptide receptor expression and function on microglia.
Main Results:
- Microglia-induced maladaptive plasticity is a significant factor in neurodegenerative and neuroinflammatory diseases.
- Neuropeptides can potently influence microglial activity both in vitro and in vivo.
- Neuropeptide administration has shown beneficial effects in experimental models of brain diseases.
Conclusions:
- Neuropeptide signaling represents a promising therapeutic avenue for managing microglia-driven pathologies.
- Targeting neuropeptide-microglia interactions could offer novel treatment strategies for various human brain disorders.
- Understanding neuropeptide modulation of microglia is crucial for developing effective neuroprotective therapies.
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