Adaptive Gene Expression Induced by a Combination of IL-1β and LPS in Primary Cultures of Mouse Astrocytes

Astrocytes are vital cells within the central nervous system (CNS), as they perform a critical role in supporting neurons by providing nutrients, such as lactate for energy, and safeguarding them against the toxicity of excessive neurotransmitters, such as glutamate. This study investigates astrocyte adaptive mechanisms in response to chronic inflammation. The primary aim is to assess the long-term effects of an inflammation-induced environment using a combination of lipopolysaccharide (LPS) and interleukin-1β (IL-1β), on the expression of key genes involved in essential metabolic pathways for astrocyte function, including glutamate metabolism and clearance, lactate synthesis and transport, and glucose metabolism. We observed an upregulation of the glutamate transporter <i>eaat2</i> (but not <i>eaat1</i>), leading to glutamate accumulation and altered glutamate-glutamine cycling, as well as increased glycolytic activity and lactate production/export via hexokinases (<i>hk1</i> and <i>hk2</i>) and the <i>mct4</i> lactate transporter. Interestingly, these mechanisms are reversible, indicating a precisely controlled adaptive system. This investigation facilitated the identification of the signaling pathways involved in astrocyte adaptive responses to stress. This will further guide our investigations towards the more complex domain of resistance and adaptation of CNS in pathophysiological conditions.