Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis
| Autor: | Paola Cavalla, Giovanni Luigi Mancardi, Claudia Trebini, Dario Giobbe, Silvia Masera, Roberto Mutani, Silvia Grifoni, Carlotta Chiavazza, Alessandra Mattioda, Laura Caligiana, Maria Teresa Giordana, Alberto Romagnolo, Elisabetta Capello, Marco Vercellino |
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| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Enzyme-Linked Immunosorbent Assay Inflammation Neuropathology multiple sclerosis Neuroprotection 03 medical and health sciences Progranulins 0302 clinical medicine Cerebrospinal fluid Neurotrophic factors progranulin medicine Humans biochemistry 030212 general & internal medicine neuropathology Microglia business.industry Macrophages Multiple sclerosis Brain medicine.disease Immunohistochemistry medicine.anatomical_structure Neurology Intercellular Signaling Peptides and Proteins Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Multiple Sclerosis Journal. 17:1194-1201 |
| ISSN: | 1477-0970 1352-4585 |
| DOI: | 10.1177/1352458511406164 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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