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Type: Artigo de periódico
Title: Jak2 Inhibition Is Neuroprotective And Reduces Astrogliosis After Quinolinic Acid Striatal Lesion In Adult Mice.
Author: Ignarro, Raffaela Silvestre
Vieira, André Schwambach
Sartori, Cesar Renato
Langone, Francesco
Rogério, Fábio
Parada, Carlos Amilcar
Abstract: Quinolinic acid (QA) striatal lesion in rodents induces neuronal death, astrogliosis and migration of neuroblasts from subventricular zone to damaged striatum. These phenomena occur in some human neurodegenerative illnesses, but the underlying mechanisms are unknown. We investigated the effect of AG490, a Janus-kinase 2 (JAK2) inhibitor, on astrogliosis, neuronal loss and neurogenesis in the striatum of adult mice after unilateral infusion of QA (30 nmol). Animals were given subcutaneous injections of AG490 (10 mg/kg) or vehicle immediately after lesion and then once daily for six days. Brain sections were used for neuronal stereological quantification, immunohistochemical and Western Blotting analyses for GFAP and doublecortin, markers of astrocytes and neuroblasts, respectively. The total area of doublecortin-positive cells (ADPC) and the number of neurons (NN) in the lesioned (L) and contralateral (CL) sides were evaluated. Neurogenesis index (NI=ADPC(L)/ADPC(CL)) and neuronal ratio (NR=NN(L)/NN(CL)) were calculated. After QA administration, blotting for GFAP showed an ipsilateral decrease of 19% in AG490- vs vehicle-treated animals. NR was 25% higher in mice given AG490 vs controls given vehicle. NI showed a decrease of 21% in AG490- vs vehicle-treated mice. Our results indicate that JAK2 inhibition reduces QA lesion and suggest that astrogliosis may impair neuronal survival in this model.
Subject: Animals
Blotting, Western
Cell Count
Cell Death
Enzyme Inhibitors
Glial Fibrillary Acidic Protein
Janus Kinase 2
Mice, Inbred C57bl
Microtubule-associated Proteins
Neurodegenerative Diseases
Neuroprotective Agents
Quinolinic Acid
Stat Transcription Factors
Signal Transduction
Citation: Journal Of Chemical Neuroanatomy. v. 48-49, p. 14-22, 2013-Mar.
Rights: fechado
Identifier DOI: 10.1016/j.jchemneu.2013.02.005
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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