Age Stability of Human Brain 5-HT Terminals Studied with [&lt;sup&gt;3&lt;/sup&gt;H]Paroxetine Binding

The effect of age on the monoamines 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA), their metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3,4-dihydroxphenylacetic acid (DOPAC), and the 5-HT precursor 5-hydroxy-L-tryptophan (5-HTP), together with the peptides neuropeptide Y (NPY), somatostatin (SOM), and corticotropin-releasing factor (CRF), was studied in frontal cortex, gyrus cinguli and hypothalamus from 23 healthy control subjects, aged 16-75 years. After correcting for postmortem interval, significant decreases in gyrus cinguli NA, NPY and CRF, and hypothalamic DA, HVA, and 5-HIAA concentrations were obtained with advancing age. The involvement of the monoaminergic system in several functional abnormalities appearing in senescence is suggested. Furthermore, evidence is given of the participation of the peptidergic systems in the aging process.

Section: The Serotonergic Systemsupporting

confidence: 84%

Brain monoaminergic and neuropeptidergic variations in human aging

Arranz

Blennow²,

Ekman³

et al. 1996

“…Importantly, as in a previous study (Andersson et al, 1992), no relationship could be found in this study between either the affinity or the density of [3H]paroxetine binding with the age of the donor or the PMI for the tissue. As [3H]paroxetine is a highly selective ligand for the serotonin transporter (Habert et al, 1985;Mellerup et al, 1986;Marcusson et al, 1988), these data indicate that the serotonin transporter is a stable molecule which is suitable for study using autopsy tissue.…”

Section: Discussioncontrasting

confidence: 48%

Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine

Naylor¹,

Dean²,

Opeskin

et al. 1996

[3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd = 0.50 +/- 0.04 vs. 0.24 +/- 0.02nM; mean +/- S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd = 0.50 +/- 0.07 vs. 0.50 +/- 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.

“…These findings show concordancy upon the different brain regions studied, and are in agreement with data reported by other researchers (Lawrence et al, 1990;Andersson et al, 1992) who did not find any significant differences in human brains from suicide victims. Similar results with respect to age-related changes have been reported for both [3H]imipramine and [3H]paroxetine binding sites, which may indicate the stability of the 5-HT terminals with increasing age in the human brain (Andersson and Marcusson, 1990;Andersson et al, 1992).…”

Section: Discussionsupporting

confidence: 93%

High affinity [3H]imipramine and [3H]paroxetine binding sites in suicide brains

Rosel

Arranz

Vallejo

et al. 1997

Specific binding of [3H]imipramine and [3H]paroxetine was simultaneously examined in human brains (frontal cortex, temporal cortex, cingulate cortex, hypothalamus, hippocampus and amygdala) from 11 controls and 11 depressed suicide victims. A single saturable high affinity site was obtained for both radioligands. Age was not related to significant changes in [3H]imipramine and [3H]paroxetine binding parameters, which indicates the stability of the brain serotonergic system with increasing age. A major finding of the present study concerns the existence of a significant decrease in the maximum number (Bmax) of [3H]imipramine binding sites in hippocampus from depressed suicides as compared with the control group, without changes in the binding affinity (Kd). In contrast, when [3H]paroxetine was used as radioligand, no changes in either Bmax or Kd were detected in any of the brain regions studied. These findings suggest that [3H]imipramine may be a better marker than [3H]paroxetine when alterations in the presynaptic serotonergic uptake site are to be detected.