Early P2X7R-related astrogliosis in autoimmune encephalomyelitis

Astrocytes are the main cells responsible for maintenance of brain homeostasis. Undisturbed action and signaling with other cells are crucial for proper functioning of the central nervous system (CNS). Dysfunctional astrocytes may determine the degree of neuronal injury and are associated with several brain pathologies, among which are multiple sclerosis (MS) and the animal model of this disease which is known as experimental autoimmune encephalomyelitis (EAE). One of the many functions of astrocytes is their response to CNS damage when they undergo reactive gliosis. Our data reveal that activation of astrocytes occurs in forebrains of immunized rats at a very early stage of EAE, well before the symptomatic phase of the disease. We have noted enhanced expression of GFAP and S100β starting from day 4 post-immunization. Temporal coincidence between the expression of astrocyte activation markers and the expression of connexin 43 and purinergic P2X7 receptor (P2X7R) was also observed. Administration of Brilliant blue G, an antagonist of P2X7R, significantly decreases astrogliosis as confirmed by immunohistochemical analysis and observation of decreased levels of GFAP and S100β. The condition of the treated animals was improved and the neurological symptoms of the disease were alleviated. With the knowledge that cerebral astroglia represent the main source of ATP and glutamate which are potentially neurotoxic substances released through P2X7R and connexin hemichannels, we suggest that astroglia may be involved in pathogenesis of MS/EAE at a very early stage through the purinergic/glutamatergic mechanisms.