An extensive microglial-astrocyte-monocyte-neuronal cross talk seems to be crucial for normal brain function, development, and recovery. However, under certain conditions neuroinflammatory interactions between brain cells and neuroimmune cells influence disease outcome and brain pathology. Microglial cells express a range of functional states with dynamically pleomorphic profiles from a surveilling status of synaptic transmission to an active player in major events of development such as synaptic elimination, regeneration, and repair. Also, inflammation mediates a series of neurotoxic roles in neuropsychiatric conditions and neurodegenerative diseases. The present review discusses data on the involvement of neuroinflammatory conditions that alter neuroimmune interactions in four different pathologies. In the first section of this review, we discuss the ability of the early developing brain to respond to a focal lesion with a rapid compensatory plasticity of intact axons and the role of microglial activation and proinflammatory cytokines in brain repair. In the second section, we present data of neuroinflammation and neurodegenerative disorders and discuss the role of reactive astrocytes in motor neuron toxicity and the progression of amyotrophic lateral sclerosis. In the third section, we discuss major depressive disorders as the consequence of dysfunctional interactions between neural and immune signals that result in increased peripheral immune responses and increase proinflammatory cytokines. In the last section, we discuss autism spectrum disorders and altered brain circuitries that emerge from abnormal long-term responses of innate inflammatory cytokines and microglial phenotypic dysfunctions.

Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial–immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre- and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.

Neuron–glia interactions are fundamental to the development and function of the nervous system. During development, glia, including astrocytes, microglia, and oligodendrocytes, influence neuronal differentiation and migration, synapse formation and refinement, and myelination. In the mature brain, glia are crucial for maintaining neural homeostasis, modulating synaptic activity, and supporting metabolic functions. Neurons, inherently vulnerable to various stressors, rely on glia for protection and repair. However, glia, in their reactive state, can also promote neuronal damage, which contributes to neurodegenerative and neuropsychiatric diseases. Understanding the dual role of glia—as both protectors and potential aggressors—sheds light on their complex contributions to disease etiology and pathology. By appropriately modulating glial activity, it may be possible to mitigate neurodegeneration and restore neuronal function. In this review, which originated from the International Society for Neurochemistry (ISN) Advanced School in 2019 held in Montreal, Canada, we first describe the critical importance of glia in the development and maintenance of a healthy nervous system as well as their contributions to neuronal damage and neurological disorders. We then discuss potential strategies to modulate glial activity during disease to protect and promote a properly functioning nervous system. We propose that targeting glial cells presents a promising therapeutic avenue for rebuilding the nervous system. image

Discussing substance abuse, licit or not, requires dynamism when it comes to adolescents. Games are a powerful tool to bring the subject up for discussion. Here we describe a collaborative board game designed to address this subject using current neuroscience knowledge about neurophysiology of (drug) addiction. The game highlights the action of 22 neuroactive drugs, classified into the following groups: (1) depressants; (2) hallucinogens; (3) stimulants and (4) others (anabolic steroids and prescription drugs). In addition, the game was developed to approach specific neuroscience-related themes such as: (1) brain structures (e.g. lobes); (2) cell types present in the nervous system; (3) neurotransmitter actions; (4) impact of drug abuse on the nervous system function; (5) the concept of overdose. Moreover, the game has got an educational proposal that combines the individual and social aspects of development, addressing concepts of neurosciences in a playful and stimulating way, aiming to promote not only awareness regarding the abuse of chemical substances, but also to stimulate the social development of the participants at the same time. It is worth mentioning that drug cards also bring curiosities and cultural trivia, including music and art, making it more attractive for young audiences.