Galanin-like immunoreactivity is unchanged in Alzheimer's disease and Parkinson's disease dementia cerebral cortex.

Galanin is a recently isolated neuropeptide that is of particular interest in dementing disorders because of its known colocalization with choline acetyltransferase in magnocellular neurons of the basal nucleus of Meynert. These neurons degenerate in Alzheimer's disease, and there is a corresponding deficiency of cortical choline acetyltransferase activity. In the present study, galanin-like immunoreactivity was measured in the postmortem cerebral cortex and hippocampus of 10 controls and 14 patients who had had Alzheimer's disease. Significant reductions of choline acetyltransferase activity (50-60%) were found in all regions examined; however, there was no significant effect on concentrations of galanin-like immunoreactivity. Similar measurements were made in postmortem tissues of 12 control and 13 demented Parkinsonian patients who had had Alzheimer-type cortical pathology. Choline acetyltransferase activity was again significantly decreased in all regions examined but there were no significant reductions in galanin-like immunoreactivity. Experimental lesions of the fornix in rats produced parallel significantly correlated reductions of both choline acetyltransferase activity and galanin-like immunoreactivity in the hippocampus. Galanin-like immunoreactivity in the human hypothalamus consisted of two molecular-weight species on gel-permeation chromatography, and two forms were resolved by reverse-phase HPLC. The paradoxical preservation of galanin-like immunoreactivity, despite depletion of the activity of choline acetyltransferase, with which it is colocalized, is as yet unexplained. Recent studies have shown that galanin inhibits both acetylcholine release in the hippocampus and memory acquisition; therefore, preserved galanin may exacerbate the cholinergic and cognitive deficits that accompany dementia.

Effect of cysteamine on somatostatin and neuropeptide Y in rat striatum and cortical synaptosomes.

Local injection of cysteamine into rat striatum results in a rapid but reversible reduction in somatostatin-like immunoreactivity (SLI). Since somatostatin and neuropeptide Y are co-localized in striatal and cortical neurons, we examined the effects of cysteamine in these areas. SLI and neuropeptide Y-like immunoreactivity (NPYLI) were measured following local injection of cysteamine into the striatum. In addition, we examined the effects of cysteamine on SLI and NPYLI in cortical synaptosomes. SLI was significantly reduced in both experiments, but NPYLI was unaffected. These results suggest that the mechanism by which somatostatin is depleted by cysteamine is one of specific biochemical modification, probably affecting the somatostatin disulfide bond, rather than one affecting neuronal metabolism.

Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease.

Neuropeptide Y is a 36-amino acid peptide that is found in high concentrations in cerebral cortex and is contained in cortical neurons. We measured concentrations of this peptide in postmortem tissue from patients with Alzheimer's disease and controls using a sensitive and specific radioimmunoassay. High-performance liquid chromatography showed that more than 95% of immunoreactivity co-migrated with synthetic standards in both Alzheimer's disease and control frontal cortex. Significant reductions in neuropeptide Y-like immunoreactivity were found in eleven cortical regions, the hippocampus, and the locus ceruleus. The regions particularly affected included the temporal lobe, frontal lobe, and occipital cortex. As neuropeptide Y is co-localized with somatostatin in a considerable proportion of cortical neurons, the loss of immunoreactivity may in part reflect degeneration of these neurons. Further study of the selective vulnerability of these neurons in Alzheimer's disease cortex may provide clues to the nature of the underlying disease process.

A comparison of regional somatostatin and neuropeptide Y distribution in rat striatum and brain.

Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were detected using specific radioimmunoassays in extracts from rat brain. Since we have previously found a topographic distribution of SLI in rat striatum the distribution of NPYLI was examined in the same regions. NPYLI showed an identical distribution to SLI in rat striatum and levels were significantly correlated (r = 0.93, P less than 0.01). Concentrations of both neuropeptides were consistently highest in ventromedial striatum and nucleus accumbens while they were lowest in dorsolateral striatum. These findings provide further evidence of neurochemical heterogeneity in the striatum. Concentrations of NPYLI and SLI were also significantly correlated in cerebral cortex (r = 0.99, P less than 0.01). Concentrations of NPYLI were generally higher than SLI and showed a similar predilection for limbic system nuclei. The present findings support the concept that somatostatin and neuropeptide Y may be co-localized in both striatal and cortical neurons.

An examination of neuropeptide Y postmortem stability in an animal model simulating human autopsy conditions.

A rabbit antiserum to neuropeptide Y (NPY) was used to develop a radioimmunoassay for measuring NPY in brain tissue. By high-performance liquid chromatography, two peaks of immunoreactivity were detected in human postmortem cortex. A minor peak was seen at the void volume, while the majority of immunoreactivity comigrated with synthetic NPY standards. Using the Spokes-Koch rat model simulating human autopsy conditions, it was shown that cortical, hippocampal and striatal concentrations of NPY-like immunoreactivity are stable for up to 24 h.