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HPA axis activity in multiple sclerosis correlates with disease severity, lesion type and gene expression in normal-appearing white matter

Acta neuropathologica, 2013-08, Vol.126 (2), p.237-249 [Peer Reviewed Journal]

Springer-Verlag Berlin Heidelberg 2013 ;COPYRIGHT 2013 Springer ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-013-1140-7 ;PMID: 23812288

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Title:
HPA axis activity in multiple sclerosis correlates with disease severity, lesion type and gene expression in normal-appearing white matter
Author: Melief, Jeroen ; de Wit, Stella J. ; van Eden, Corbert G. ; Teunissen, Charlotte ; Hamann, Jörg ; Uitdehaag, Bernard M. ; Swaab, Dick ; Huitinga, Inge
Subjects: ACTH ; Adult ; Aged ; Aged, 80 and over ; CD163 antigen ; Cerebrospinal Fluid - physiology ; Corticosteroids ; Corticotropin releasing hormone ; Corticotropin-Releasing Hormone - cerebrospinal fluid ; Corticotropin-Releasing Hormone - metabolism ; Depression, Mental ; Development and progression ; Female ; Gene expression ; Gene Expression - physiology ; Genes ; Glutamate ; Glutamic Acid - cerebrospinal fluid ; Glutamic Acid - metabolism ; Humans ; Hydrocortisone - cerebrospinal fluid ; Hydrocortisone - metabolism ; Hypothalamo-Hypophyseal System - pathology ; Hypothalamo-Hypophyseal System - physiopathology ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mood Disorders - pathology ; Mood Disorders - physiopathology ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Multiple Sclerosis - pathology ; Multiple Sclerosis - physiopathology ; Nerve Degeneration - pathology ; Nerve Degeneration - physiopathology ; Nerve Fibers, Myelinated - pathology ; Nerve Fibers, Myelinated - physiology ; Neurofilament Proteins - cerebrospinal fluid ; Neurofilament Proteins - metabolism ; Neurons - metabolism ; Neurons - pathology ; Neurosciences ; Original Paper ; Pathology ; Pituitary-Adrenal System - pathology ; Pituitary-Adrenal System - physiopathology ; Severity of Illness Index ; tau Proteins - cerebrospinal fluid ; tau Proteins - metabolism ; Tissue Banks ; Transcriptome
Is Part Of: Acta neuropathologica, 2013-08, Vol.126 (2), p.237-249
Description: The hypothalamus–pituitary–adrenal (HPA) axis is activated in most, but not all multiple sclerosis (MS) patients and is implicated in disease progression and comorbid mood disorders. In this post-mortem study, we investigated how HPA axis activity in MS is related to disease severity, neurodegeneration, depression, lesion pathology and gene expression in normal-appearing white matter (NAWM). In 42 MS patients, HPA axis activity was determined by measuring cortisol in cerebrospinal fluid (CSF) and counting hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons. Degree of neurodegeneration was based on levels of glutamate, tau and neurofilament in CSF. Duration of MS and time to EDSS 6 served as indicators of disease severity. Glutamate levels correlated with numbers of CRH-expressing neurons, most prominently in primary progressive MS patients, suggesting that neurodegeneration is a strong determinant of HPA axis activity. High cortisol levels were associated with slower disease progression, especially in females with secondary progressive MS. Patients with low cortisol levels had greater numbers of active lesions and tended towards having less remyelinated plaques than patients with high cortisol levels. Interestingly, NAWM of patients with high cortisol levels displayed elevated expression of glucocorticoid-responsive genes, such as CD163, and decreased expression of pro-inflammatory genes, such as tumor necrosis factor-α. Thus, HPA axis hyperactivity in MS coincides with low inflammation and/or high neurodegeneration, and may impact on lesion pathology and molecular mechanisms in NAWM and thereby be of great importance for suppression of disease activity.
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
Language: English
Identifier: ISSN: 0001-6322
EISSN: 1432-0533
DOI: 10.1007/s00401-013-1140-7
PMID: 23812288
Source: ProQuest One Psychology
MEDLINE
Alma/SFX Local Collection
ProQuest Central

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HPA axis activity in multiple sclerosis correlates with disease severity, lesion type and gene expression in normal-appearing white matter

Springer-Verlag Berlin Heidelberg 2013 ;COPYRIGHT 2013 Springer ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-013-1140-7 ;PMID: 23812288

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