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Lactate has received attention as a potential therapeutic intervention for brain diseases, particularly those including energy deficit, exacerbated inflammation, and disrupted redox status, such as cerebral ischemia. However, lactate roles in metabolic or signaling pathways in neural cells remain elusive in the hypoxic and ischemic contexts. Here, we tested the effects of lactate on the survival of a microglial (BV-2) and a neuronal (SH-SY5Y) cell lines during oxygen and glucose deprivation (OGD) or OGD followed by reoxygenation (OGD/R). Lactate signaling was studied by using 3,5-DHBA, an exogenous agonist of lactate receptor GPR81. Inhibition of lactate dehydrogenase (LDH) or monocarboxylate transporters (MCT), using oxamate or 4-CIN, respectively, was performed to evaluate the impact of lactate metabolization and transport on cell viability. The OGD lasted 6 h and the reoxygenation lasted 24 h following OGD (OGD/R). Cell viability, extracellular lactate concentrations, microglial intracellular pH and TNF-ɑ release, and neurite elongation were evaluated. Lactate or 3,5-DHBA treatment during OGD increased microglial survival during reoxygenation. Inhibition of lactate metabolism and transport impaired microglial and neuronal viability. OGD led to intracellular acidification in BV-2 cells, and reoxygenation increased the release of TNF-ɑ, which was reverted by lactate and 3,5-DHBA treatment. Our results suggest that lactate plays a dual role in OGD, acting as a metabolic and a signaling molecule in BV-2 and SH-SY5Y cells. Lactate metabolism and transport are vital for cell survival during OGD. Moreover, lactate treatment and GPR81 activation during OGD promote long-term adaptations that potentially protect cells against secondary cell death during reoxygenation.

Since the first evidence suggesting that maternal nutrition can impact the development of diseases in the offspring, much has been elucidated about its effects on the offspring’s nervous system. Animal studies demonstrated that maternal obesity can predispose the offspring to greater chances of metabolic and neurodevelopmental diseases. However, the mechanisms underlying these responses are not well established. In recent years, the role of the gut-brain axis in the development of anxiety and depression in people with obesity has emerged. Studies investigating changes in the maternal microbiota during pregnancy and also in the offspring demonstrate that conditions such as maternal obesity can modulate the microbiota, leading to long-term outcomes in the offspring. Considering that maternal obesity has also been linked to the development of psychiatric conditions (anxiety and depression), the gut-brain axis is a promising target to be further explored in these neuropsychiatric contexts. In the present study, we review the relationship between maternal obesity and anxious and depressive features, exploring the gut-brain axis as a potential mechanism underlying this relationship.

Since the first studies of the nervous system by the Nobel laureates Camillo Golgi and Santiago Ramon y Cajal using simple dyes and conventional light microscopes, microscopy has come a long way to the most recent techniques that make it possible to perform images in live cells and animals in health and disease. Many pathological conditions of the central nervous system have already been linked to inflammatory responses. In this scenario, several available markers and techniques can help imaging and unveil the neuroinflammatory process. Moreover, microscopy imaging techniques have become even more necessary to validate the large quantity of data generated in the era of 'omics'. This review aims to highlight how to assess neuroinflammation by using microscopy as a tool to provide specific details about the cell's architecture during neuroinflammatory conditions. First, we describe specific markers that have been used in light microscopy studies and that are widely applied to unravel and describe neuroinflammatory mechanisms in distinct conditions. Then, we discuss some important methodologies that facilitate the imaging of these markers, such as immunohistochemistry and immunofluorescence techniques. Emphasis will be given to studies using two-photon microscopy, an approach that revolutionized the real-time assessment of neuroinflammatory processes. Finally, some studies integrating omics with microscopy will be presented. The fusion of these techniques is developing, but the high amount of data generated from these applications will certainly improve comprehension of the molecular mechanisms involved in neuroinflammation.

Since the first studies of the nervous system by the Nobel laureates Camillo Golgi and Santiago Ramon y Cajal using simple dyes and conventional light microscopes, microscopy has come a long way to the most recent techniques that make it possible to perform images in live cells and animals in health and disease. Many pathological conditions of the central nervous system have already been linked to inflammatory responses. In this scenario, several available markers and techniques can help imaging and unveil the neuroinflammatory process. Moreover, microscopy imaging techniques have become even more necessary to validate the large quantity of data generated in the era of 'omics'. This review aims to highlight how to assess neuroinflammation by using microscopy as a tool to provide specific details about the cell's architecture during neuroinflammatory conditions. First, we describe specific markers that have been used in light microscopy studies and that are widely applied to unravel and describe neuroinflammatory mechanisms in distinct conditions. Then, we discuss some important methodologies that facilitate the imaging of these markers, such as immunohistochemistry and immunofluorescence techniques. Emphasis will be given to studies using two-photon microscopy, an approach that revolutionized the real-time assessment of neuroinflammatory processes. Finally, some studies integrating omics with microscopy will be presented. The fusion of these techniques is developing, but the high amount of data generated from these applications will certainly improve comprehension of the molecular mechanisms involved in neuroinflammation.