Increased number of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of patients with multiple sclerosis.
Observations in experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis (MS), have indicated that a low activity of the hypothalamo-pituitary-adrenal (HPA) system is accompanied by a high susceptibility for EAE in rat strains and that elevated corticosteroid levels are necessary for spontaneous recovery from EAE. The HPA axis activity is regulated by both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both types of neurons are localized in the paraventricular nucleus (PVN) of the hypothalamus. We determined the number of immunocytochemically identified CRH-immunoreactive (CRH-IR) and AVP-immunoreactive (AVP-IR) neurons in the PVN of the human hypothalamus of 8 MS patients, aged 34-63 years, and 8 age-matched control subjects without any primary neurological or psychiatric disorders, aged 30-59 years. In addition, the number of oxytocin (OXT) immunoreactive (OXT-IR) neurons was determined, since these neurons innervate brain stem nuclei and might thus be related to autonomic disturbances in MS. In MS the staining intensity for AVP was clearly lower and for OXT slightly lower. For CRH, the staining intensity was similar in both groups, and, moreover, in MS patients the number of CRH-IR cells in the PVN was found to be about 2.4 times higher than that in the control group. The number of OXT-IR or AVP-IR cells in the PVN of MS patients was not significantly different from that of the control group. Our results point to an activation of the neuroendocrine HPA axis which may be compatible with the idea that the HPA axis is involved in recovery from MS.(ABSTRACT TRUNCATED AT 250 WORDS)
Purba
J S
JS
Graduate School of Neurosciences, The Netherlands Institute for Brain Research, Amsterdam.
Raadsheer
F C
FC
Hofman
M A
MA
Ravid
R
R
Polman
C H
CH
Kamphorst
W
W
Swaab
D F
DF
D000328:Adult; D001127:Arginine Vasopressin / Q000276:immunology; D002452:Cell Count; D003346:Corticotropin-Releasing Hormone / Q000276:immunology*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000276:immunology / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009474:Neurons / Q000276:immunology*; D010286:Paraventricular Hypothalamic Nucleus / Q000473:pathology*
D001127:Arginine Vasopressin; D003346:Corticotropin-Releasing Hormone