Human brain cytosolic histamine-N-methyltransferase is decreased in Down syndrome and increased in Pick's disease.
Histamine-N-methyltransferase (HMT) inactivates the neurotransmitter histamine. Central histaminergic deficits may contribute to the cognitive impairment of neurodegenerative disorders including Alzheimer's disease (AD) and Down syndrome (DS). However, there is no evidence for histaminergic deficits in Pick's disease (PiD). HMT levels were measured in the frontal cortex and cerebellum of brains of patients with AD, DS, and PiD, and normal aged subjects using proteomics techniques. In frontal cortex, HMT was significantly decreased in DS, but significantly increased in PiD compared with controls. HMT levels were comparable in cerebellum of all groups. Elevated HMT in PiD could lead to increased histamine degradation that in turn would be in agreement with impaired cognitive functions of PiD. Decreased HMT in DS would be compatible with findings of decreased histamine synthesis, thus reflecting a compensation mechanism to antagonize reduced synthesis by decreased degradation.
Kim
Seong Hwan
SH
Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A-1090 Vienna, Austria.
Krapfenbauer
Kurt
K
Cheon
Myeong Sook
MS
Fountoulakis
Michael
M
Cairns
Nigel J
NJ
Lubec
Gert
G
D000368:Aged; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003600:Cytosol / Q000201:enzymology*; D004314:Down Syndrome / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006632:Histamine / Q000378:metabolism*; D006637:Histamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D020774:Pick Disease of the Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
D006632:Histamine; D006637:Histamine N-Methyltransferase