PMID- 14705110
OWN - NLM
STAT- MEDLINE
DCOM- 20040312
LR  - 20220318
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 55
IP  - 1
DP  - 2004 Jan
TI  - Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple 
      sclerosis with hypothalamic lesions.
PG  - 37-45
AB  - In this postmortem study, we investigated the relationship between multiple 
      sclerosis (MS) lesions in the hypothalamus and the state of activity of 
      corticotropin-releasing hormone (CRH)-producing neurons that control the 
      hypothalamus-pituitary-adrenal (HPA) axis. A high incidence (15/16) of MS lesions 
      was found in the hypothalamus, of which more than 50% was active, that is, 
      contained activated macrophages. MS patients have increased numbers of 
      CRH-immunoreactive neurons coexpressing vasopressin (CRH/VP neurons), a sign of 
      chronic activation of CRH neurons and increased CRH mRNA expression. Active MS 
      lesions correlated with a low number of hyperactive CRH/VP neurons. High human 
      leukocyte antigen (HLA)-DR, -DP, -DQ expression, a measure for macrophage and 
      microglial activation, correlated with low CRH mRNA expression. The nearer the 
      HLA expression was situated to the CRH neurons, the stronger the inhibiting 
      effect, suggesting that activated microglial cells or macrophages suppress these 
      neurons. The more active MS lesions were present in the hypothalamus, the shorter 
      was the disease duration until the moment of death, indicating an unfavorable 
      course of the disease. Thus, MS patients have a chronically activated CRH system, 
      but, in the subgroup of patients with active MS lesions in the hypothalamus, this 
      activation is impaired and the disease course is worse.
FAU - Huitinga, Inge
AU  - Huitinga I
AD  - Netherlands Institute for Brain Research, Amsterdam, The Netherlands. 
      i.huitinga@nih.knaw.nl
FAU - Erkut, Zeynel A
AU  - Erkut ZA
FAU - van Beurden, Denis
AU  - van Beurden D
FAU - Swaab, Dick F
AU  - Swaab DF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (HLA Antigens)
RN  - 0 (RNA, Messenger)
RN  - 11000-17-2 (Vasopressins)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Corticotropin-Releasing Hormone/metabolism
MH  - Female
MH  - HLA Antigens/physiology
MH  - Humans
MH  - Hypothalamo-Hypophyseal System/*physiopathology
MH  - Hypothalamus/metabolism/*pathology
MH  - Image Processing, Computer-Assisted
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Macrophage Activation/physiology
MH  - Male
MH  - Microglia/physiology
MH  - Middle Aged
MH  - Multiple Sclerosis/*pathology/physiopathology
MH  - Neurons/*metabolism
MH  - Pituitary-Adrenal System/*physiopathology
MH  - RNA, Messenger/analysis
MH  - Vasopressins/metabolism
EDAT- 2004/01/06 05:00
MHDA- 2004/03/16 05:00
CRDT- 2004/01/06 05:00
PHST- 2004/01/06 05:00 [pubmed]
PHST- 2004/03/16 05:00 [medline]
PHST- 2004/01/06 05:00 [entrez]
AID - 10.1002/ana.10766 [doi]
PST - ppublish
SO  - Ann Neurol. 2004 Jan;55(1):37-45. doi: 10.1002/ana.10766.