TY - JOUR
T1 - Functional increase of brain histaminergic signaling in Huntington's disease
AU - van Wamelen, Daniel J.
AU - Shan, Ling
AU - Aziz, N. Ahmad
AU - Anink, Jasper J.
AU - Bao, Ai-Min
AU - Roos, Raymund A. C.
AU - Swaab, Dick F.
PY - 2011
Y1 - 2011
N2 - To evaluate whether central histaminergic signaling in Huntington's disease (HD) patients is affected, we assessed mRNA levels of histidine decarboxylase (HDC), volume of and neuron number in the hypothalamic tuberomamillary nucleus (TMN) (HD n = 8, controls n = 8). In addition, we assessed histamine N-methyltransferase (HMT) and histamine receptor (H(1) R, H(2) R and H(3) R) mRNA levels in the inferior frontal gyrus (IFG) (n = 9 and 9) and caudate nucleus (CN) (n = 6 and 6) by real-time polymerase chain reaction. In HD patients, TMN volume and neuronal number was unaltered (P = 0.72, P = 0.25). The levels of HDC mRNA (P = 0.046), IFG HMT (P < 0.001), H(1) R (P < 0.001) and H(3) R mRNA levels (P = 0.011) were increased, while CN H(2) R and H(3) R mRNA levels were decreased (P = 0.041, P = 0.009). In HD patients, we observed a positive correlation between IFG H(3) R mRNA levels and CAG repeat length (P = 0.024) and negative correlations between age at onset of disease and IFG HMT (P = 0.015) and H(1) R (P = 0.021) mRNA levels. These findings indicate a functional increase in brain histaminergic signaling in HD, and provide a rationale for the use of histamine receptor antagonists
AB - To evaluate whether central histaminergic signaling in Huntington's disease (HD) patients is affected, we assessed mRNA levels of histidine decarboxylase (HDC), volume of and neuron number in the hypothalamic tuberomamillary nucleus (TMN) (HD n = 8, controls n = 8). In addition, we assessed histamine N-methyltransferase (HMT) and histamine receptor (H(1) R, H(2) R and H(3) R) mRNA levels in the inferior frontal gyrus (IFG) (n = 9 and 9) and caudate nucleus (CN) (n = 6 and 6) by real-time polymerase chain reaction. In HD patients, TMN volume and neuronal number was unaltered (P = 0.72, P = 0.25). The levels of HDC mRNA (P = 0.046), IFG HMT (P < 0.001), H(1) R (P < 0.001) and H(3) R mRNA levels (P = 0.011) were increased, while CN H(2) R and H(3) R mRNA levels were decreased (P = 0.041, P = 0.009). In HD patients, we observed a positive correlation between IFG H(3) R mRNA levels and CAG repeat length (P = 0.024) and negative correlations between age at onset of disease and IFG HMT (P = 0.015) and H(1) R (P = 0.021) mRNA levels. These findings indicate a functional increase in brain histaminergic signaling in HD, and provide a rationale for the use of histamine receptor antagonists
U2 - https://doi.org/10.1111/j.1750-3639.2010.00465.x
DO - https://doi.org/10.1111/j.1750-3639.2010.00465.x
M3 - Article
C2 - 21106039
SN - 1015-6305
VL - 21
SP - 419
EP - 427
JO - Brain pathology (Zurich, Switzerland)
JF - Brain pathology (Zurich, Switzerland)
IS - 4
ER -