Adenosine A(2A) receptor and ecto-5'-nucleotidase/CD73 are upregulated in hippocampal astrocytes of human patients with mesial temporal lobe epilepsy (MTLE)

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Paulo Correia de Sá (Autor) ICBAS

Revista

Título: Purinergic Signalling

Vol. 12

Páginas: 719-734

ISSN: 1573-9538

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 30 Citações

Scopus - 30 Citações

Outras Informações

ID Authenticus: P-00K-X8M

DOI: 10.1007/s11302-016-9535-2

Abstract (EN): Refractoriness to existing medications of up to 80 % of the patients with mesial temporal lobe epilepsy (MTLE) prompts for finding new antiepileptic drug targets. The adenosine A(2A) receptor emerges as an interesting pharmacological target since its excitatory nature partially counteracts the dominant antiepileptic role of endogenous adenosine acting via inhibitory A(1) receptors. Gain of function of the excitatory A(2A) receptor has been implicated in a significant number of brain pathologies commonly characterized by neuronal excitotoxicity. Here, we investigated changes in the expression and cellular localization of the A(2A) receptor and of the adenosine-generating enzyme, ecto-5'-nucleotidase/CD73, in the hippocampus of control individuals and MTLE human patients. Western blot analysis indicates that the A(2A) receptor is more abundant in the hippocampus of MTLE patients compared to control individuals. Immunoreactivity against the A(2A) receptor predominates in astrocytes staining positively for the glial fibrillary acidic protein (GFAP). No co-localization was observed between the A(2A) receptor and neuronal cell markers, like synaptotagmin 1/2 (nerve terminals) and neurofilament 200 (axon fibers). Hippocampal astrogliosis observed in MTLE patients was accompanied by a proportionate increase in A(2A) receptor and ecto-5'-nucleotidase/CD73 immunoreactivities. Given our data, we hypothesize that selective blockade of excessive activation of astrocytic A(2A) receptors and/or inhibition of surplus adenosine formation by membrane-bound ecto-5'-nucleotidase/CD73 may reduce neuronal excitability, thus providing a novel therapeutic target for drug-refractory seizures in MTLE patients.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16