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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

JAK2 inhibition is neuroprotective and reduces astrogliosis after quinolinic acid striatal lesion in adult mice

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Author(s):
Ignarro, Raffaela Silvestre [1] ; Vieira, Andre Schwambach [1] ; Sartori, Cesar Renato [1] ; Langone, Francesco [1] ; Rogerio, Fabio [2] ; Parada, Carlos Amilcar [1]
Total Authors: 6
Affiliation:
[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, BR-13083865 Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Dept Pathol, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Chemical Neuroanatomy; v. 48-49, p. 14-22, MAR 2013.
Web of Science Citations: 15
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. (C) 2013 Elsevier B.V. All rights reserved. (AU)