Neuroglia, Volume 6, Issue 2 (June 2025) – 7 articles

Background/Objectives: Nitric oxide (NO) and electromagnetic fields (EMFs) have been reported to influence central nervous system (CNS) function and organization. This study explores the effects of NO modulation and EMF exposure on neurodevelopment and glial fibrillary acidic protein (GFAP) expression and cell morphology, extending the prior work on perinatal EMF exposure in Wistar rats. Methods: Rats were perinatally exposed to water, 1 g/L L-arginine (LA), or 0.5 g/L N-methylarginine (NMA), along with a 7 Hz square-wave EMF at intensities of 0 nT, ≤50 nT, or 500 nT, starting three days before birth and continuing for 14 days postnatally. GFAP expression and cell morphology were analyzed via immunohistochemistry in regions including the hypothalamus, amygdala, hippocampus, and cortex. Results: Significant changes in GFAP morphology and expression are observed. A main EMF effect emerged in the right ventromedial hypothalamus, where the branch length of GFAP-expressing cells increased in EMF-exposed groups compared to the controls [t(32) = −2.52, p = 0.017]. In the hippocampus, LA exposure decreased GFAP expression in the right dentate gyrus compared to water controls [t(23) = 2.37, p = 0.027]. A sex-specific EMF effect was detected in the left CA2 hippocampus, where males exposed to EMF showed significant differences from unexposed males [t(15) = −2.90, p = 0.011]. Conclusions: These findings reveal complex interactions between EMF exposure, sex, and NO modulation, with region-specific effects on GFAP expression in the developing rat brain. Full article

Müller glia exhibit a remarkable regenerative capacity in zebrafish through spontaneous reprogramming post-injury but remain limited in mammals. This review highlights the key mechanisms underlying Müller glia reprogramming, including gene regulatory networks, cytokine signaling, signal transduction pathways, epigenetic modifications, and transcriptional regulation. Cross-species analyses have uncovered conserved gene networks that suppress neurogenesis in mammals, while injury-induced transcriptional profiles reveal divergent regenerative strategies. Combinatorial approaches may enhance the reprogramming of mammalian Müller glia into functional neurons. Nevertheless, significant challenges remain, such as variability in the efficacy of direct reprogramming methods and the limited regeneration of cone photoreceptors, even in regenerative species. We conclude that targeting epigenetic barriers and species-specific regulatory pathways offers promising avenues for clinical translation in retinal disorders such as glaucoma and retinitis pigmentosa. Moving forward, research efforts should prioritize the functional integration of regenerated neurons and the development of standardized methodologies to accelerate therapeutic advancements. Full article

Background/Objectives: The annexin A1 (AnxA1) protein has proven important in ocular disease homeostasis and holds great therapeutic promise. However, its role in the context of the healthy retina remains unknown. Therefore, this study used electroretinography (ERG) to investigate the role of endogenous AnxA1 in the retinal function of wild-type (WT) and AnxA1 knockout mice (AnxA1^−/−). Methods: An extensive repertoire of full-field ERG was applied to AnxA1^−/− and WT mice to examine retinal physiology. Morphometric analyses of the retina were conducted. Results: Our results revealed significant differences in the implicit time of a-wave and b-wave between the WT and AnxA1^−/− groups under scotopic conditions. The negative and positive amplitude components of mesopic ON responses were higher in the AnxA1^-/- group than in the WT group. In contrast, the implicit time of mesopic ON responses were significantly higher in the WT group than in the AnxA1^-/- WT group. However, in photopic OFF responses, only the implicit time was significantly longer in the WT group than in the AnxA1^−/− group. In the histomorphometric analysis, the retina of AnxA1^−/− mice shows increased thickness. Conclusions: The absence of AnxA1 alters retinal morphology and physiology. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition influenced by genetic, environmental, and epigenetic factors, leading to cognitive, emotional, and social impairments. Due to the heterogeneity of ASD, conventional therapies often have limited effectiveness, highlighting the need for complementary interventions. Enriched environments (EEs), characterized by enhanced sensory, cognitive, and motor stimulation, have shown promise in alleviating ASD symptoms. This review examines the role of glial cells in mediating the effects of EE. Methods: A literature review was conducted, analyzing studies on EE interventions in animal models and humans, with a focus on glial involvement in neuroplasticity and synaptic remodeling. Results: Evidence from animal models suggests that EE induces significant glial modifications, including increased synaptogenesis and enhanced neuronal connectivity. Studies in rodent models of ASD have demonstrated that EE reduces stereotypical behaviors, improves social interactions, and enhances cognitive function, effects that are closely associated with astrocyte and microglia activity. Similarly, human studies indicate that EE interventions lead to reduced autism symptom severity and improved cognitive outcomes, further supporting the hypothesis that glial cells play a central role in mediating the beneficial effects of EE. Conclusions: This review highlights the potential of EE as a modulator of the brain’s microenvironment, emphasizing the critical role of glial processes in ASD intervention. These findings suggest that future therapeutic strategies for ASD should integrate approaches that specifically target a glial function to optimize intervention outcomes. However, further research is needed to optimize EE protocols and address ASD heterogeneity. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, with increasing evidence supporting the role of immune dysregulation in its pathophysiology. Neuroinflammation, mediated by microglial activation, pro-inflammatory cytokine production, and blood–brain barrier dysfunction, plays a crucial role in dopaminergic neuronal degeneration. Furthermore, peripheral immune changes, including T cell infiltration, gut microbiota dysbiosis, and systemic inflammation, contribute to disease progression. The bidirectional interaction between the central and peripheral immune systems suggests that immune-based interventions may hold therapeutic potential. While dopaminergic treatments remain the standard of care, immunomodulatory therapies, monoclonal antibodies targeting α-synuclein, and deep brain stimulation (DBS) have demonstrated immunological effects, though clinical efficacy remains uncertain. Advances in immune phenotyping offer new avenues for personalized treatment approaches, optimizing therapeutic responses by stratifying patients based on inflammatory biomarkers. This review highlights the complexities of immune involvement in PD and discusses emerging strategies targeting immune pathways to develop disease-modifying treatments. Full article

In homeostasis, the glial cells support pivotal functions, such as neuronal differentiation, neuroprotection, nutrition, drug metabolism, and immune response in the central nervous system (CNS). Among these cells, astrocytes and microglia have been highlighted due to their role in the pathogenesis of several diseases or due to their role in the defense against several insults (ex., chemicals, and pathogens). In Vitro cytological analysis of astrocytes and microglia has contributed to the understanding of the role of morphological changes in glial cells associated with a neuroprotective or neurotoxic phenotype. Currently, the main tools used for the investigation of glial cell morphology in culture are phase contrast microscopy or immunolabeling/fluorescence microscopy. However, generally, phase contrast microscopy does not generate images with high resolution and therefore does not contribute to visualizing a single cell morphology in confluent cell cultures. On the other hand, immunolabeling requires high-cost consumable antibodies, epifluorescence microscope or confocal microscope, and presents critical steps during the procedure. Therefore, identifying a fast, reproducible, low-cost alternative method that allows the evaluation of glial morphology is essential, especially for neuroscientists from low-income countries. This article aims to revise the use of Rosenfeld’s staining, as an alternative low-cost and easy-to-reproduce method to analyze astrocytic and microglial morphology in culture. Additionally, it shows Rosenfeld’s staining as a valuable tool to analyze changes in neural cell morphology in toxicological studies. Full article

In recent decades, substantial evidence has highlighted the integral roles of neuroglia, particularly astrocytes, microglia, oligodendrocytes, and ependymal cells, in the regulation of synaptic transmission, metabolic support, and immune mechanisms within the central nervous system. In addition to their structural role, these cells actively modulate neurotransmitter homeostasis and influence neuronal plasticity, thereby affecting cognition, mood, and behavior. This review discusses how neuroglial alterations contribute to the pathophysiology of five common psychiatric disorders: major depression, bipolar disorder, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. We synthesized preclinical and clinical findings illustrating that glial dysfunction, including impaired myelination and aberrant neuroinflammatory responses, often parallels disease onset and severity. Moreover, we outline how disruptions in astrocytic glutamate uptake, microglia-mediated synaptic pruning, and blood–brain barrier integrity may underlie the neurobiological heterogeneity observed in these disorders. The therapeutic implications range from anti-inflammatory agents to investigational compounds that aim to stabilize glial function or promote remyelination. However, challenges due to interindividual variability, insufficient biomarkers, and the multifactorial nature of psychiatric illnesses remain. Advances in neuroimaging, liquid biopsy, and more precise molecular techniques may facilitate targeted interventions by stratifying patient subgroups with distinct glial phenotypes. Continued research is essential to translate these insights into clinically efficacious and safe treatments. Full article