41 research outputs found
Depression in the menopause transition: risks in the changing hormone milieu as observed in the general population
Galanin receptors in human basal forebrain differ from receptors in the hypothalamus: Characterization using [\u3csup\u3e125\u3c/sup\u3eI]galanin (porcine) and [\u3csup\u3e125\u3c/sup\u3eI]galantide
Galanin, a 29-amino acid peptide, is uniquely distributed in human basal forebrain and may play a role in cholinergic cell dysfunction in Alzheimer\u27s disease. We report a detailed evaluation of galanin receptors in human basal forebrain (67 ± 12 years) and hypothalamus (67 ± 15 years) with radioligand binding techniques. The binding of [125I]galanin (porcine) (agonist) or [125I]galantide [GAL (1-3)-substance P (5-11)-NH2] (putative antagonist) saturated in 2 hr, and only 15% to 30% of either radioligand was removed in the presence of unlabeled peptide. [125I]Galanin or [125I]galantide binding in basal forebrain revealed similar B(max) values, with [125I]galanin having a higher affinity for the galanin receptor. In contrast, [125I]galanin showed a lower affinity and labeled 42% more receptors than [125I]galantide in the hypothalamus. Differences were noted in competition studies of galanin and galanin chimeric peptides (M15, M35, M40 and C7) between [125I]galanin and [125I]galantide binding and in both regions. M35, M40 and C7 showed high affinity for galanin receptors in the hypothalamus with Hill coefficients close to unity, whereas in the basal forebrain these peptides competed differently. 5\u27-Guanylylimidodiphosphate reduced the specific binding of either radioligand in both regions. Based on the derived data, both radioligands irreversibly bind with high affinity and act as agonists at galanin receptors in human basal forebrain and hypothalamus. Galanin and galanin chimeric peptides compete differently for galanin receptors depending on the radioligand and region tested, suggesting subtype differences
Galanin receptor plasticity within the nucleus basalis in early and late Alzheimer\u27s disease: An in vitro autoradiographic analysis
Hypertrophy of fibers containing galanin (GAL), the inhibitory neurotransmitter of acetylcholine, occur on remaining cholinergic nucleus basalis neurons in late stage Alzheimer\u27s disease (AD). The present investigation evaluated whether changes in the number of GAL receptors (GALR) were detectable within the nucleus basalis in the early or late stage of AD when compared to age-matched controls. Postmortem neuropathological specimens were obtained at autopsy from three groups: late AD, early (possible) AD, and normal (age-matched controls) human subjects. Autoradiography of GALR binding was performed on human brain sections from each of the three groups. Analysis of autoradiographic images show no change in the distribution of ([125])hGAL binding sites in early AD cases throughout the nucleus basalis. In contrast, the number of ([125])hGAL binding sites was increased over the anterior nucleus basalis subfield in late stage AD. A region-of-interest densitometric analysis of the anterior nucleus basalis in the late stage AD cases depict an increase in the number of ([125])hGAL binding sites by approximately two-three-fold when compared to normal (age-matched controls). Quantitative measures of ([125])hGAL binding densities were not significantly different in the anterolateral, intermediate or posterior nucleus basalis subsectors of early or late stage AD when compared to age-matched controls. These observations show that the occurrence of overexpression of GALRs coincide with earlier reports showing galaninergic fibers hyperinnervating surviving cholinergic basal forebrain neurons in late stage AD. Copyright (C) 2000 Elsevier Science Ltd
Characterization and localization of galanin receptors in human entorhinal cortex
The neuropeptide galanin (GAL) has a widespread distribution throughout the human cortex. The entorhinal cortex (ENT) plays a crucial role in the transfer of cortico-cortical information related to memory and displays severe degeneration in Alzheimer\u27s disease (AD). However, very little is known about the pharmacology of the GAL receptor (GALR) in normal human ENT. Therefore, we pharmacologically visualized their distribution and characterized GALRs using in vitro receptor autoradiography and radioligand binding assays. Autoradiograms revealed intense GALR labeling, mainly in the substantia innominata, hypothalamus, the bed nucleus of the stria terminalis and within layers 2 and 4 of the ENT. Kinetic experiments showed that saturation of GALR sites by [125I]GAL (human) (hGAL) occurred within 2 h and that this binding readily reversed in the presence of a GTP analog, but not in the presence of excess unlabeled hGAL. Analysis of [125I]hGAL binding data from saturation experiments gave K(D) values of 98.6±21.6 pM, B(max) values of 52.9±32.4 fmol/mg protein and identified a high and low affinity state of the GALR. The presence of 5\u27-guanylylimidodiphosphate (GppNHp) or NaCl reduced the agonist labeling of hGALR in ENT membranes. Copyright (C) 1998 Elsevier Science B.V