Intrinsic ecto-5'-Nucleotidase/A 1 R Coupling may Confer Neuroprotection to the Cerebellum in Experimental Autoimmune Encephalomyelitis

• Published in: Molecular neurobiology 2024-11, Vol.61 (11), p.9284
• Main Authors: Stekic, Andjela, Stevic, Dejan, Dokmanovic, Tamara, Anastasov, Marina, Popovic, Danica, Stanojevic, Jelena, Jovanovic, Milica Zeljkovic, Stevanovic, Ivana, Nedeljkovic, Nadezda, Dragic, Milorad
• Format: Article
• Language: English
• Subjects: 5'-Nucleotidase - metabolism; Adenosine Deaminase - metabolism; Animals; Astrocytes - metabolism; Astrocytes - pathology; Cerebellum - metabolism; Cerebellum - pathology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Gliosis - metabolism; Gliosis - pathology; Mice; Mice, Inbred C57BL; Neuroprotection; Receptor, Adenosine A1 - metabolism; Receptor, Adenosine A2A - metabolism
• ISSN: 1559-1182
• DOI: 10.1007/s12035-024-04174-9

Experimental autoimmune encephalomyelitis (EAE) is widely used animal model of multiple sclerosis (MS). The disease is characterized by demyelination and neurodegeneration triggered by infiltrated autoimmune cells and their interaction with astrocytes and microglia. While neuroinflammation is most common in the spinal cord and brainstem, it is less prevalent in the cerebellum, where it predisposes to rapid disease progression. Because the induction and progression of EAE are tightly regulated by adenosinergic signaling, in the present study we compared the adenosine-producing and -degrading enzymes, ecto-5'-nucleotidase (eN/CD73) and adenosine deaminase (ADA), as well as the expression levels of adenosine receptors A R and A R subtypes in nearby areas around the fourth cerebral ventricle-the pontine tegmentum, the choroid plexus (CP), and the cerebellum. Significant differences in histopathological findings were observed between pontine tegmentum and cerebellum on the same horizontal section level. Reactive astrogliosis and massive infiltration of CD4 + cells and macrophages in CP and pontine tegmentum resulted in local demyelination. In cerebellum, there was no evidence of infiltrates, microgliosis and neuroinflammation at the same sectional level. In addition, Bergman glia showed no signs of reactive gliosis. As for adenosinergic signaling, significant upregulation of eN/CD73 was observed in all areas studied, but in association with different adenosine receptor subtypes. In CP and pons, overexpression of eN/CD73 was coupled with induction of A R, whereas in cerebellum, a modest increase in eN/CD73 in resident Bergman glia was accompanied by a strong induction of A R in the same type of astrocytes. Thus, the presence of specialized astroglia and intrinsic differences in adenosinergic signaling may play a critical role in the differential regional susceptibility to EAE inflammation.