GABA transporters (GAT-1) in Alzheimer's disease.

The presynaptically located gamma-aminobutyric acid (GABA) transporter (GAT-1) was studied in a group of patients with Alzheimer's disease (AD) and in a control group using the GAT-1 selective radioligand [3H]tiagabine. Post mortem brain tissue from frontal cortex, temporal cortex, and caudate nucleus from 18 AD patients and 23 age-matched controls were studied. The binding was saturable (Kd 26 nM) and region specific. There were no significant differences between the groups with respect to the binding capacity (Bmax) and binding affinity (Kd). The unaltered [3H]tiagabine binding to GAT-1 protein indicates that intrinsic GABA neurons are spared in Alzheimer's disease.

Serotonergic, noradrenergic, and dopaminergic measures in suicide brains.

Concentrations of the three main monoamines (5-HT, NA, and DA), their metabolites (5-HIAA, DOPAC, and HVA), and the serotonin precursor 5-hydroxy-L-tryptophan were simultaneously measured in frontal cortex, gyrus cinguli, and hypothalamus from 23 controls and 18 suicide victims. Overall suicides did not show significant differences with respect to the control group in any of the measured compounds. Significant increases in noradrenaline and dopamine concentrations were noted in the carbon monoxide poisoning suicides, together with a significant increased hypothalamic dopamine in the drug overdose suicides. It is suggested that the suicidal behavior is not related to substantial changes in cortical and hypothalamic monoaminergic function; however, the reported results could be secondary to the rapid effect of hypoxia and of the acute self-administration of certain drugs in specific metabolic pathways.

Gamma-aminobutyric acid-B (GABAB) binding sites in postmortem suicide brains.

Gamma-aminobutyric acid-B (GABAB) binding sites labelled with [3H]GABA were determined in postmortem frontal cortex samples of 20 control subjects and 16 suicides. The suicide group was further subdivided according to the method of suicide and the existence of depressive symptoms prior to death. No significant differences in GABAB binding were found either between overall suicide and control groups or between the control group and the other subgroups (violent suicide, nonviolent suicide, nondepressed and depressed suicide victims). A significant increase in GABAB binding was observed in those individuals dying from carbon monoxide poisoning. It is concluded that although GABAB binding sites are not altered in our suicide group, a presynaptic dysfunction might account for the increased GABAB binding found in the carbon monoxide subgroup.

Elevated density of [3H]imipramine binding in aged human brain.

Aging was associated with an increase in the density of specific binding sites for [3H]imipramine in postmortem specimens of human hypothalamus, frontal cortex, and parietal cortex. In general, [3H]imipramine binding was not affected by factors considered difficult to control in postmortem studies, i.e., time from death to autopsy and cause of death. The in vitro regulation of [3H]imipramine binding by sodium was impaired with age in hypothalamic homogenates. In vitro regulation of [3H]imipramine binding by chloride was intact. Determination of the concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid in hypothalamus and frontal cortex indicated no apparent age-related changes in indole metabolism. The age-related increase in brain [3H]imipramine binding and impairment in the in vitro regulation of binding by ions are similar to changes observed previously in aged mouse brain. The increase in brain antidepressant binding sites is discussed in relationship to other indices of brain serotonergic function in aging and to the relationship of [3H]imipramine binding and depression.

Genetic aspects of psoriasis: mode of inheritance and action of PUVA on DNA.

The results of some family and experimental studies related to psoriasis are summarized. Complex segregation analysis of Lomholt's classical family material of psoriasis from the Faroe Islands gave clear evidence of a major locus (additive gene with a frequency of 0.07) plus a strong polygenic component (genetic heritability 0.87). An analysis of another family material showed complete linkage between the major locus for psoriasis and the HLA region. Treatment of cells with 8-methoxypsoralene plus a small dose of UVA induces monoadducts, some of which appear to remain in the DNA for at least 7 days of post-treatment incubation. These monoadducts can be activated to form DNA cross-links by a second, larger UVA dose. 8-Methoxypsoralene plus UVA-induced DNA cross-links can be modified by a repair process which involves the formation of DNA breaks. This process in not observed in XPA cells.