FROM SELENIUM TO SYNAPSE: UNDERSTANDING THE IMPACT OF SELENIUM DEFICIENCY ON PARVALBUMIN INTERNEURONS AND PERINEURONAL NETS IN CORTICAL CULTURES
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2024
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Parvalbumin interneurons (PVIs) are a critical subgroup of GABAergic interneurons involved in neural circuitry. They are integral to generating and modulating gamma oscillations, which are necessary for enhancing information processing by reducing circuit noise and amplifying circuit signals. During development, these interneurons are surrounded by unique extracellular matrix structures called perineuronal nets (PNNs). In neurodevelopmental disorders such as Schizophrenia (SCZ), evidence has pointed to damage or loss in both PVIs and PNNs, and a possible culprit is increased oxidative stress, particularly during development. Selenoproteins, a unique clade of proteins identified by the incorporation of the amino acid selenocysteine, are necessary for PVI development. Most selenoproteins are antioxidant enzymes and several, such as GPX4 and SELENOP, are important to PVI development. This relationship between selenoproteins and PVIs has been explored in depth using several knockout (KO) mouse models. However, more research is needed to understand the involvement of nutritional selenium (Se) for maturing PVIs. Additionally, no studies have examined the role of selenium or selenoproteins in the development of PNNs. Here, using in vitro cultures of primary cortical tissue, we show that Se-deficiency driven by reduced bioavailable selenium, decreases the expression of critical antioxidant selenoproteins, drives oxidative stress in PVIs, and reduces the number of mature PNNs. Critically, we find that Se-deficiency influences the formation of synapses around PNN positive PVIs. This results in changes to cortical network activity, which has broad implications for our understanding and emphasizes the importance of micronutrients in developing the central nervous system (CNS).
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Cellular biology, Molecular biology, Neurosciences, GABAergic Interneuron, Oxidative Stress, Parvalbumin Interneuron, Perineuronal Net, Selenium, Selenoprotein
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119 pages
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