Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UMLS:C0036341 (
schizophrenia
)
60,220
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We previously identified a group of subjects with
schizophrenia
who, on average, have a 75% decrease in
cholinergic receptor, muscarinic 1
(
CHRM1
) in Brodmann's area (BA) 9. To extend this finding, we determined i) if the decrease in
CHRM1
was present in another functionally related CNS region (BA6), ii) whether the marked decrease in
CHRM1
was accompanied by changes in levels of other CHRMs and iii) potential factors responsible for the decreased
CHRM1
expression. We measured
CHRM1
and CHRM3 using in situ radioligand binding with [(3)H]pirenzepine and [(3)H]4-DAMP respectively in BA6 from 20 subjects with
schizophrenia
who had low levels of
CHRM1
in BA9 (SzLow[(3)H]PZP), 18 subjects with
schizophrenia
whose levels of
CHRM1
were similar to controls (SzNormal[(3)H]PZP) and 20 control subjects. Levels of
CHRM1
, 3 and 4 mRNA were measured using qPCR and levels of the transcription factors, SP1 and SP3, were determined using Western blots. In BA6, the density of [(3)H]pirenzepine binding was decreased in subjects with SzLow[(3)H]PZP (p<0.001) compared to controls. The density of [(3)H]4-DAMP binding, levels of
CHRM1
, 3 and 4 mRNA and levels of SP1 and SP3 was not significantly different between the three groups. This study shows that the previously identified decrease in
CHRM1
expression is not confined to the dorsolateral prefrontal cortex but is present in other cortical areas. The effect shows some specificity to
CHRM1
, with no change in levels of binding to CHRM3. Furthermore, this decrease in
CHRM1
does not appear to be associated with low levels of
CHRM1
mRNA or to simply be regulated by the transcription factors, SP1 and SP3, suggesting that other mechanisms are responsible for the decreased
CHRM1
in these subjects.
...
PMID:An investigation of the factors that regulate muscarinic receptor expression in schizophrenia. 2503 27
