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Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis.
MedLine Citation:
PMID:  21613335     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Progranulin (PGRN) is a fundamental neurotrophic factor, and is also involved in inflammation and wound repair. PGRN may have pro- or anti-inflammatory properties, depending upon proteolysis of the anti-inflammatory parent PGRN protein and the generation of pro-inflammatory granulin peptides. Objectives: Our objectives were as follows: (1) to evaluate the presence and distribution of PGRN in multiple sclerosis (MS) brain tissue, correlating it with demyelination and inflammation; (2) to evaluate cerebrospinal fluid (CSF) PGRN concentrations in patients with MS and controls, in relationship to the clinical features of the disease. Methods: Our study involved the following: (1) neuropathological study of PGRN on post-mortem tissue of 19 MS and six control brains; (2) evaluation of PGRN CSF concentration in 40 MS patients, 15 non-inflammatory controls and five inflammatory controls (viral encephalitis). Results: In active demyelinating lesions, PGRN was expressed on macrophages/microglia. In the normal-appearing white matter (NAWM), expression of PGRN was observed on activated microglia. PGRN was expressed by neurons and microglia in cortical lesions and in normal-appearing cortex. No expression of PGRN was observed in controls, except on neurons. PGRN CSF concentrations were significantly higher in patients with relapsing-remitting MS during relapses and in progressive MS patients, compared with relapsing-remitting MS patients during remissions and with non-inflammatory controls. Conclusions: PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS.
Authors:
Marco Vercellino; Silvia Grifoni; Alberto Romagnolo; Silvia Masera; Alessandra Mattioda; Claudia Trebini; Carlotta Chiavazza; Laura Caligiana; Elisabetta Capello; Giovanni Luigi Mancardi; Dario Giobbe; Roberto Mutani; Maria Teresa Giordana; Paola Cavalla
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-25
Journal Detail:
Title:  Multiple sclerosis (Houndmills, Basingstoke, England)     Volume:  -     ISSN:  1477-0970     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9509185     Medline TA:  Mult Scler     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neuroscience, AOU S. Giovanni Battista di Torino, Turin, Italy.
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