Victoria Chan-Palay

Cholecystokinin-octapeptide (CCK-8) receptors in the hippocampal region: a comparative in vitro autoradiographic study in the rat, monkey and the postmortem human brain

Quantitative in vitro receptor autoradiography of 125I-CCK-8 was used to study the regional distribution of CCK-8 receptors in the primate hippocampal region. In the monkey, specific 125I-CCK-8 binding sites were enriched in layer 2 of the presubiculum, layers 1, 2, and 4 of the entorhinal area and in the inner two-thirds of the molecular layer of the area dentata. Moderate to low densities were detected in layer 3 of the entorhinal area, the deep layers of the presubiculum, all layers of subiculum and subfields CA1 and CA3 of Ammons horn. In the human brain, the highest densities of 125I-CCK-8 binding sites were detected in layer 2 of the presubiculum and layer 2 of the lateral entorhinal area. Moderate to low levels were detected in the Ammons horn and area dentata. This pattern of receptor distribution overlaps only partly with that found in the rat and indicates phylogenetic differences in the localization of CCK-8 receptors within the hippocampal region.

Cholinergic Neurons of the Nucleus basalis Express Elevated Levels of Nerve Growth Factor Receptor mRNA in Senile Dementia of the Alzheimer Type

Magnocellular cholinergic neurons in the nucleus basalis of Meynert (nbM) undergo a profound and selective degeneration in patients with senile dementia of the Alzheimer type (SDAT). We show by in sit

Galanin receptors in the post-mortem human brain. Regional distribution of 125I-galanin binding sites using the method of in vitro receptor autoradiography

The distribution of putative receptors for the peptide galanin was studied in the normal post-mortem human brain by using 125I-galanin (0.5 nM) in combination with in vitro receptor autoradiography. Specific binding of 125I-galanin was found in a large number of brain areas throughout the neuraxis. Highest binding densities occurred in the basal forebrain and hypothalamus, while the basal ganglia, major parts of the thalamus and the tectum were found to be poor in binding sites. All cortical areas harboured 125I-galanin binding, and in the visual cortex a laminated pattern was present. In the hippocampus, 125I-galanin binding occurred in layer 2 of the entorhinal cortex, in the uncus and in the hippocampal-amygdala area. In the brain-stem, 125I-galanin binding was found in serotoninergic noradrenergic cell groups as well as in the reticular formation and in the parabrachial nuclei. Galanin receptors may, thus, mediate the response of galanin in numerous structures in the human brain.

Dopamine D2 receptors in the rat, monkey and the post-mortem human hippocampus. An autoradiographic study using the novel D2-selective ligand 125I-NCQ 298

The distribution of dopamine D2 receptors in the hippocampal region of the rat, monkey and the postmortem human brain was studied with in vitro receptor autoradiography using the selective salicylamide ligand 125I-NCQ 298. Specific binding was defined in the presence of the D2-selective compound raclopride. In all 3 species, higher densities of specifically bound 125I-NCQ 298 was found in the retrohippocampal structures than in the hippocampus proper. In the rat, layers 1 and 3 of the entorhinal cortex and layer 2 of the presubiculum were found to be rich in specific binding sites. In the monkey, the highest densities were detected in the deep layers (4 through 6) of the entorhinal cortex (EC) and in layer 2 of the presubiculum. Relatively high density of binding was found in the granule cell layer of area dentata. In the human brain, less specific binding was seen as compared to the other two species; the highest densities occurred in the outer layers of the presubiculum and in the hilus of area dentata. These findings show that D2 receptors are present in the hippocampal region and that the retrohippocampal region, including the entorhinal cortex, is enriched in dopamine D2 receptors.

Immunocytochemistry of human brain tissue with a polyclonal antiserum against neuropeptide Y.

SummaryNPY-containing neuronal structures in the cereoral cortex of surgical tissue samples were compared to those in postmortem material by immunocytochemical methods. However, the quality of preservation of individual neurons and axonal and dendritic plexuses in the neuropil is unusually fine in the surgical specimens. This result is most likely attributable to the excellent fixation that can be regularly achieved by rapid and careful handling of tissue during and after surgical removal. The tissue is suitable for both light and electron microscopy, and the superior preservation also leads to intense, reliable antibody reactions. Postmortem tissue samples can provide good specimens for immunocytochemistry when properly handled as previously described. However the postmortem delays prior to fixation disrupt neuronal integrity in the immunostained structures. Nevertheless, postmortem material from carefully studied subjects of neurological diseases compared with age matched controls can provide valuable information.

Calbindin D-28k and Monoamine Oxidase A Immunoreactive Neurons in the Nucleus Basalis of Meynert in Senile Dementia of the Alzheimer Type and Parkinson's Disease

In this study, calbindin D-28k (CaBP), monoamine oxidase A (MAO A) and nerve growth factor receptor (NGFr) immunoreactivities were investigated in the nucleus basalis of Meynert (NbM) in patients with senile dementia of the Alzheimer type (SDAT), with Parkinsons disease (PD) with or without dementia, and in controls. Immunocytochemistry using specific antibodies in differing serial sections was employed, and cell counts and NbM nuclear volume measurements were made. Most of the large multipolar NbM neurons showed CaBP immunoreactivity in the cytoplasm of their somata, dendrites and axons. In adjacent, NGFr-reacted sections, the large NbM neurons were also found to be intensely immunoreactive for NGFr on their cellular surfaces. In addition, a subpopulation of large NbM neurons and glial cells were found to be immunoreactive for MAO A. The number of CaBP-immunoreactive (CaBP-i) neurons was decreased by an average of 55% in the 6 SDAT patients, 70% in the 2 nondemented PD patients and 40% in the 1 demented PD patient. The volume calculated for the compact part of the NbM formed by the CaBP-i neuronal somata decreased by an average of 47% in SDAT. On the other hand, measurements in the volume of NGFr-i neurons (including the dendritic arborization) showed an average decrease of 25% in SDAT patients compared to controls. Although all SDAT and PD patients showed a decrease of CaBP-i neurons in the NbM, a loss of MAO-A-i NbM neurons was found only in those patients with dementia. Therefore, the relative proportions of MAO-A-i to CaBP-i neurons were increased in the nondemented PD patients (14.2 and 19.6%) when compared with those in the demented PD patient (2.2%) and with the SDAT patients (0.3-5.6%). These data indicate that a balanced presence of MAO-A-i cholinergic, large NbM neurons may be necessary for the proper maintenance of cognitive function. Functionally this may be translated to mean that dementing changes may cause a decrease from the normal amount of MAO A enzyme activity. This suggests that therapeutic strategies based upon correction of MAO-A activities by MAO-A inhibitors may be important to ameliorating some of the loss in cholinergic function in dementias of SDAT and PD.

Distribution of Neuropeptide Y, C-Terminal Flanking Peptide of NPY and Galanin and Coexistence with Catecholamine in the Locus coeruleus of Normal Human, Alzheimer's Dementia and Parkinson's Disease Brains

The study demonstrates the presence of neuropeptide Y (NPY)-, C-terminal flanking peptide of NPY (C-PON)-, and galanin (GA)-immunoreactive (-i) neurons and axons in the locus coeruleus in normal adult

Raphe Serotonin Neurons in the Human Brain Stem in Normal Controls and Patients with Senile Dementia of the Alzheimer Type and Parkinson's Disease: Relationship to Monoamine Oxidase Enzyme Localization (Part 1 of 3)

The raphe serotonin system was studied in patients with senile dementia of the Alzheimer type (SDAT) or with Parkinsons disease and compared with normal controls. Postmortem brain stems were cut in c

Distribution of neurotensin receptors in the primate hippocampal region: a quantitative autoradiographic study in the monkey and the postmortem human brain

The distribution of [3H]neurotensin ([3H]NT) binding sites in the monkey and the postmortem human brain was studied by using quantitative in vitro receptor autoradiography. Biochemical experiments carried out on tissue sections of the monkey hippocampus showed that the binding of [3H]NT was saturable, reversible and of high specificity. The hippocampal [3H]NT binding was displaced by fragment NT 8-13 but not fragment NT 1-8 of the peptide. The anatomical analysis showed a highly heterogeneous distribution of [3H]NT binding sites within both the monkey and the human hippocampal region. In both species the highest density of [3H]NT binding sites was found in the presubiculum (rank order of binding density: layer 2 greater than 6 greater than 1 greater than 3, 4, 5 in both monkey and man) and the entorhinal area (monkey: layer 4 greater than 6 greater than 5 greater than 1 greater than 2 greater than 3; human: layer 1 = 2 greater than 5 greater than 3). The subiculum and Ammons horn were relatively poor in [3H]NT binding sites in both species. In the area dentata the highest density of [3H]NT binding sites was found in the hilar region.

Distribution of serotonin-1A receptors in the monkey and the postmortem human hippocampal region. A quantitative autoradiographic study using the selective agonist [3H]8-OH-DPAT

Serotonin-1A receptors were visualized and their anatomical distribution mapped within the monkey and the human hippocampus by using in vitro receptor autoradiography of the selective agonist [3H]8-OH-N,N-dipropyl-2-aminotetralin ([3H]8-OH-DPAT). The results show high densities of serotonin-1A receptors heterogeneously distributed in different subfields and layers of the monkey and the human hippocampal region. High densities are found in the molecular layer of area dentata, all layers of regio superior and the subiculum, parasubiculum, and layers 2, and 4 through 6 of the entorhinal area. In the human hippocampus, a distinct band of [3H]8-OH-DPAT binding sites is present in the subgranular zone of the area dentata. The similar anatomical distribution of [3H]8-OH-DPAT binding sites in the monkey and the human hippocampal region suggests that the serotonin-1A receptor is phylogenetically well preserved and indicates that this receptor may mediate action(s) of serotonin in the primate, including the human hippocampal region.