5-Hydroxytryptamine-sensitive [3H]imipramine binding of protein nature in the human brain. II. Effect of normal aging and dementia disorders.
Recently, a high-affinity [3H]imipramine binding site of protein nature that appeared related to the 5-hydroxytryptamine (5-HT, serotonin) uptake mechanism was demonstrated in the rat brain. In a preceding paper a similar [3H]imipramine binding site of protein nature and displaceable by 5-HT was demonstrated in the human brain. Most previous [3H]imipramine binding studies of the human brain have used desipramine-sensitive binding, which appears to contain a significant amount of additional binding not related to 5-HT neurons. Therefore this study of the human brain in the normal aging, in Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) and in multiinfarction dementia (MID) presents data on 5-HT-sensitive [3H]imipramine binding. The influence of normal aging (17-100 years) was studied in the frontal and cingulate cortices, in the putamen, caudate nucleus, amygdala and in the hippocampus. An age-related change in 5-HT-sensitive [3H]imipramine binding was only noted in the cingulate cortex with a 50% loss in Bmax over the adult age range. In contrast, desipramine-sensitive [3H]imipramine binding studied in the frontal cortex and in the putamen showed marked increases in Bmax with age which correlated with increases in Kd. It is suggested that these increases are related to an increased binding to lipophilic membrane components not related to 5-HT neurons. The 5-HT-sensitive [3H]imipramine binding (Bmax) was reduced to 60% of control in the cingulate cortex and to 50% in the putamen in AD/SDAT. In MID there was a 50% loss of [3H]imipramine binding sites (Bmax) in the putamen, but a 30% loss in the cingulate cortex did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathology, University of Umeå, Sweden.
J O
JO
Marcusson
I
I
Alafuzoff
I T
IT
Bäckström
E
E
Ericson
C G
CG
Gottfries
B
B
Winblad
D000368:Aged; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D006801:Humans; D007099:Imipramine / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D012701:Serotonin / Q000494:pharmacology*; D014316:Tritium
D009419:Nerve Tissue Proteins; D014316:Tritium; D012701:Serotonin; D007099:Imipramine