Fundamental Neurochemistry Review: Lipids across microglial states.

The capacity of immune cells to alter their function based on their metabolism is the basis of the emerging field of immunometabolism. Microglia are the resident innate immune cells of the central nervous system, and it is a current focus of the field to investigate how alterations in their metabolism impact these cells. Microglia have the ability to utilize lipids, such as fatty acids, as energy sources, but also alterations in lipids can impact microglial form and function.

Microglia degrade Alzheimer's amyloid-beta deposits extracellularly via digestive exophagy.

How microglia digest Alzheimer's fibrillar amyloid-beta (Aβ) plaques that are too large to be phagocytosed is not well understood. Here, we show that primary microglial cells create acidic extracellular compartments, lysosomal synapses, on model plaques and digest them with exocytosed lysosomal enzymes. This mechanism, called digestive exophagy, is confirmed by electron microscopy in 5xFAD mouse brains, which shows that a lysosomal enzyme, acid phosphatase, is secreted toward the plaques in structures resembling lysosomal synapses.

Female mice exhibit similar long-term plasticity and microglial properties between the dorsal and ventral hippocampal poles.

The hippocampus is a heterogenous structure that exhibits functional segregation along its longitudinal axis. We recently showed that in male mice, microglia, the brain's resident immune cells, differ between the dorsal (DH) and ventral (VH) hippocampus, impacting long-term potentiation (LTP) mainly through the CX3CL1-CX3CR1 signaling. Here, we assessed the specific features of the hippocampal poles in female mice, demonstrating a similar LTP amplitude in VH and DH in both control and Cx3cr1 knock-out mice.

Ultrastructural features of psychological stress resilience in the brain: a microglial perspective.

Psychological stress is the major risk factor for major depressive disorder. Sustained stress causes changes in behaviour, brain connectivity and in its cells and organelles. Resilience to stress is understood as the ability to recover from stress in a positive way or the resistance to the negative effects of psychological stress.

Abstinence from cocaine self-administration promotes microglia pruning of astrocytes which drives cocaine-seeking behavior.

Rodent drug self-administration leads to compromised ability of astrocytes to maintain glutamate homeostasis within the brain's reward circuitry, as well as reductions in surface area, volume, and synaptic colocalization of astrocyte membranes. However, the mechanisms driving astrocyte responses to cocaine are unknown. Here, we report that long-access cocaine self-administration followed by prolonged home cage abstinence results in decreased branching complexity of nucleus accumbens astrocytes, characterized by the loss of peripheral processes.

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis.

Lipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) .

Microglia in Neurodegenerative Diseases.

Neurodegenerative diseases are manifested by a progressive death of neural cells, resulting in the deterioration of central nervous system (CNS) functions, ultimately leading to specific behavioural and cognitive symptoms associated with affected brain regions. Several neurodegenerative disorders are caused by genetic variants or mutations, although the majority of cases are sporadic and linked to various environmental risk factors, with yet an unknown aetiology. Neuroglial changes are fundamental and often lead to the pathophysiology of neurodegenerative diseases.

Microglia and Sleep Disorders.

Sleep is a physiological state that is essential for maintaining physical and mental health. Sleep disorders and sleep deprivation therefore have many adverse effects, including an increased risk of metabolic diseases and a decline in cognitive function that may be implicated in the long-term development of neurodegenerative diseases. There is increasing evidence that microglia, the resident immune cells of the central nervous system (CNS), are involved in regulating the sleep-wake cycle and the CNS response to sleep alteration and deprivation.

Microglia and Microbiome-Gut-Brain Axis.

The mammalian gut contains a community of microorganisms called gut microbiome. The gut microbiome is integrated into mammalian physiology, contributing to metabolism, production of metabolites, and promoting immunomodulatory actions. Microglia, the brain's resident innate immune cells, play an essential role in homeostatic neurogenesis, synaptic remodeling, and glial maturation.

Adult Neurogenesis, Learning and Memory.

Neural plasticity can be defined as the ability of neural circuits to be shaped by external and internal factors. It provides the brain with a capacity for functional and morphological remodelling, with many lines of evidence indicating that these changes are vital for learning and memory formation. The basis of this brain plasticity resides in activity- and experience-driven modifications of synaptic strength, including synaptic formation, elimination or weakening, as well as of modulation of neuronal population, which drive the structural reorganization of neural networks.

Synapse Regulation.

Microglia are the resident immune cells of the brain. As such, they rapidly detect changes in normal brain homeostasis and accurately respond by fine-tuning in a tightly regulated manner their morphology, gene expression, and functional behavior. Depending on the nature of these changes, microglia can thicken and retract their processes, proliferate and migrate, release numerous signaling factors and compounds influencing neuronal physiology (e.

General Pathophysiology of Microglia.

Microglia, which are the resident innate immune cells of the central nervous system (CNS), have emerged as critical for maintaining health by not only ensuring proper development, activity, and plasticity of neurones and glial cells but also maintaining and restoring homeostasis when faced with various challenges across the lifespan. This chapter is dedicated to the current understanding of microglia, including their beneficial versus detrimental roles, which are highly complex, rely on various microglial states, and intimately depend on their spatiotemporal context. Microglia are first contextualized within the perspective of finding therapeutic strategies to cure diseases in the twenty-first century-the overall functions of neuroglia with relation one to another and to neurones, and their shared CNS environment.

Bone marrow-derived myeloid cells transiently colonize the brain during postnatal development and interact with glutamatergic synapses.

Although the roles of embryonic yolk sac-derived, resident microglia in neurodevelopment were extensively studied, the possible involvement of bone marrow-derived cells remains elusive. In this work, we used a fate-mapping strategy to selectively label bone marrow-derived cells and their progeny in the brain (FLT3IBA1). FLT3IBA1 cells were confirmed to be transiently present in the healthy brain during early postnatal development.

Fibulin-2 is an extracellular matrix inhibitor of oligodendrocytes relevant to multiple sclerosis.

Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS), stroke, and Alzheimer's disease. Regeneration of myelin (remyelination) decreases the vulnerability of demyelinated axons, but this repair process commonly fails with disease progression. A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions, which remains to be better defined.

The emerging neuroimmune hypothesis of bipolar disorder: An updated overview of neuroimmune and microglial findings.

Bipolar disorder (BD) is a severe and multifactorial disease, with onset usually in young adulthood, which follows a progressive course throughout life. Replicated epidemiological studies have suggested inflammatory mechanisms and neuroimmune risk factors as primary contributors to the onset and development of BD. While not all patients display overt markers of inflammation, significant evidence suggests that aberrant immune signaling contributes to all stages of the disease and seems to be mood phase dependent, likely explaining the heterogeneity of findings observed in this population.

Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies.

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies.

Established and emerging techniques for the study of microglia: visualization, depletion, and fate mapping.

The central nervous system (CNS) is an essential hub for neuronal communication. As a major component of the CNS, glial cells are vital in the maintenance and regulation of neuronal network dynamics. Research on microglia, the resident innate immune cells of the CNS, has advanced considerably in recent years, and our understanding of their diverse functions continues to grow.