Biomedical subjects

G Paxinos

Publications and source records attributed to G Paxinos.

At least 37 records · Page 2Linked to original sources

PubMed1996

On the distribution of cholecystokinin B receptors in monkey brain.

In view of recent evidence for a role for the B subtype of cholecystokinin (CCKB) receptor in panic and anxiety, the distribution of CCKB receptors in the forebrain of a Rhesus macaca monkey was examined by receptor autoradiography employing [125I]D-Tyr25(Nleu28,31)-CCK25-33S. CCKB receptors were widely and topographically distributed in cortex. Other structures with notable labelling included the basal ganglia, presubiculum, amygdala, mamillary bodies, cerebellar cortex and pineal gland. The distribution of CCKB receptors further supports roles for this peptide in behavioural processes.

Animals↗

PubMed1996

Distribution of AT4 receptors in the Macaca fascicularis brain.

Angiotensin IV (Val Tyr Ile His Pro Phe), administered centrally, increases memory retrieval and induces c-fos expression in the hippocampus and piriform cortex. Angiotensin IV binds to a high affinity site that is quite distinct in pharmacology and distribution from the angiotensin II AT1 and AT2 receptors and is known as the AT4 receptor. These observations suggest that the AT4 receptor may have multiple central effects. The present study uses in vitro receptor autoradiography, and employs [125I]angiotensin IV to map AT4 receptors in the macaca fascicularis brain. The distribution of the AT4 receptor is remarkable in that its distribution extends throughout several neural systems. Most striking is its localization in motor nuclei and motor associated regions. These include the ventral horn spinal motor neurons, all cranial motor nuclei including the oculomotor, abducens, facial and hypoglossal nuclei, and the dorsal motor nucleus of the vagus. Receptors are also present in the vestibular, reticular and inferior olivary nuclei, the granular layer of the cerebellum, and the Betz cells of the motor cortex. Moderate AT4 receptor density is seen in all cerebellar nuclei, ventral thalamic nuclei and the substantia nigra pars compacta, with lower receptor density observed in the caudate nucleus and putamen. Abundant AT4 receptors are also found in areas associated with cholinergic nuclei and their projections, including the nucleus basalis of Meynert, ventral limb of the diagonal band and the hippocampus, somatic motor nuclei and autonomic preganglionic motor nuclei. AT4 receptors are also observed in sensory regions, with moderate levels in spinal trigeminal, gracile, cuneate and thalamic ventral posterior nuclei, and the somatosensory cortex. The abundance of the AT4 receptor in motor and cholinergic neurons, and to a lesser extent, in sensory neurons, suggests multiple roles for the AT4 receptor in the primate brain.

Acetylcholinesterase↗

PubMed1996

Interactions of angiotensin II with central dopamine.

There is a large body of evidence to support the concept of a relationship between brain Ang II and catecholamine systems. This interaction may participate in some central actions of Ang II such as cardiovascular control, dipsogenesis, and complex behaviours. It also extends to the nigrostriatal dopaminergic system which bear AT1 receptors, both on their cell bodies in the substantia nigra presynaptically, and on their terminals in the striatum, where Ang II can markedly potentiate DA release. This observation suggests that drugs which modulate central Ang II may be useful in regulating central dopaminergic activity.

Angiotensin II↗

PubMed1995

Human intermediate reticular zone: a cyto- and chemoarchitectonic study.

The primary aim of this study was to provide a comprehensive account of the morphology, topography, and frequency of tyrosine hydroxylase- and substance P-like (TH-LI, SP-LI) immunoreactive neurons of the human intermediate reticular zone (IRt), the putative autonomic zone of the medullary reticular formation. A further aim is to examine the IRt from a three-dimensional perspective using computer reconstruction techniques and compare its relationship with other structures in the rest of the medullary reticular formation. Six adult human brains were obtained from individuals with no sign of cerebral disease and were perfusion fixed. Free-floating transverse sections were immunostained with monoclonal antibodies against tyrosine hydroxylase and substance P by the avidin-biotin-peroxidase technique. The entire IRt displays TH-LI cell bodies and fibers, and thus it is readily distinguishable from the neighbouring gigantocellular and parvicellular reticular nuclei. In contrast, SP-LI cells are restricted to the external part of the IRt that is found in the open medulla, while SP-LI fibers are more widely distributed. The IRt displays TH-LI neurons which are fusiform, oval, and round in shape. The SP-LI neurons of the IRt are primarily oval and fusiform. In preparations stained for Nissl substance, IRt cells were classified as pigmented and nonpigmented. A characteristic feature of the IRt is that its cells are larger (20 +/- 4 micrograms) than those of the laterally adjoining parvicellular (12 +/- 2 micrograms) and clearly smaller than those of the medially adjoining gigantocellular nuclei (33 +/- 6 micrograms). The shape of the IRt is in keeping with the radial organization of the medulla with zones emanating from the fourth ventricle. Three-dimensional computer reconstructions of the cell plots show that 1) TH-LI neurons extend through the entire IRt and densely packed in the rostral part of the ventrolateral IRt and 2) SP-LI neurons are found only in the rostral half of the medulla oblongata.

Aged↗

PubMed1995

Angiotensin II receptor subtypes in the human central nervous system.

The distribution of the AT1 and AT2 subtypes of angiotensin II receptor was mapped in the adult human central nervous system using quantitative in vitro autoradiography. Binding in all forebrain, midbrain, pontine, medullary and spinal cord sites where angiotensin II receptors have previously been described is of the AT1 subtype, as is binding in the small and large arteries in the adjacent meninges and in choroid plexus. By contrast, both AT1 and AT2 receptors occur in the molecular layer of the cerebellum. Angiotensin II AT1 receptors in the brain show a moderate degree of conservation across mammalian species studied so far, whereas expression of AT2 receptors is more variable, and is more restricted in the human CNS than in many other mammals. These differences between the subtype distributions in humans and other animals indicate the need for care when extrapolating the results of animal studies involving the brain angiotensin system.

Aged↗

PubMed1995

Localization of angiotensin converting enzyme by in vitro autoradiography in the rabbit brain.

The distribution of angiotensin converting enzyme was examined in the rabbit brain by in vitro autoradiography with the specific radiolabelled inhibitor 125I-351A. In the rabbit, the highest concentrations of radioligand binding were found in the choroid plexus, blood vessels, subfornical organ, vascular organ of the lamina terminalis, area postrema and inferior olive. High levels of binding were found throughout the basal ganglia, consistent with the results in all other species studied. In the midbrain the central gray and the superior colliculus displayed high levels of binding. In the medulla oblongata high levels of binding were associated with the nucleus of the solitary tract and dorsal motor nucleus of vagus, consistent with the pattern in other species. There was moderate labelling throughout both the cerebral and cerebellar cortices, which contrasts to the rat but is consistent with the situation in primates. Angiotensin converting enzyme (ACE) is more widely distributed in rabbit brain that in rat, human and Macaca fascicularis, and the results suggest ACE has a very general role in the metabolism of neuropeptides. Inhibitors of converting enzyme are very widely used in the treatment of hypertension and heart disease, and the rabbit should provide a useful model for examining the effects of these drugs in the brain.

Animals↗

PubMed1995

Comparative distribution of receptors for amylin and the related peptides calcitonin gene related peptide and calcitonin in rat and monkey brain.

The distribution of amylin receptors (125I-labelled rat amylin) in brains of rat and monkey were mapped and compared with the distribution of receptors for calcitonin (CT) (125I-labelled salmon CT) and calcitonin gene related peptide (CGRP) (rat, 125I-labelled rat CGRP alpha; monkey, 125I-labelled human CGRP alpha. In rat, amylin receptors were discretely distributed with the highest receptor densities found in mid-caudal accumbens nucleus, parts of the bed nucleus of the stria terminalis, amygdala, and hypothalamus. Moderate to high densities of binding also occurred in the area postrema, subfornical organ, vascular organ of the lamina terminalis, locus ceruleus, dorsal raphe, and caudal solitary tract nucleus. In monkey, the distribution of amylin binding sites was similar, although the highest densities of receptors were in the hypothalamus, with relatively fewer sites present in the accumbens nucleus. In rat, the distribution of amylin receptors formed a subset of the receptor distributions for 125I-labelled salmon CT and 125I-labelled rat CGRP alpha. In contrast, in monkey, although the amylin receptors again formed a subset of the binding sites identified with 125I-labelled salmon CT, there was very little overlap with the pattern of CGRP receptor distribution. This suggests that the specificity profile of amylin receptors in primates differs from that of amylin receptors in the rat, with CGRP alpha having relatively lower affinity for the primate amylin receptors.

Animals↗

PubMed1994

The supraoculomotor cap: a region revealed by NADPH diaphorase histochemistry.

The distribution of the enzyme NADPH diaphorase in the region of the periaqueductal gray (PAG) was studied in the rat, rabbit, cat, monkey and human. In each species, the enzyme labelled a small band of neurones located below the level of the aqueduct and directly above the supraoculomotor gray in the middle of the antero-posterior extent of the PAG. The chemical specificity of this region suggests that it is distinct from the lateral PAG above and the supraoculomotor nucleus (Su3) below. We have named it the supraoculomotor cap (Su3C).

Animals↗

PubMed1994

In vitro autoradiographic localization of calcitonin binding sites in human medulla oblongata.

In this study we examined the distribution of calcitonin (CT) binding sites in the human medulla oblongata by in vitro autoradiography. In competition studies, the rank order of potency for calcitonins competing for 125I-salmon CT binding was salmon CT > porcine CT > human CT, which is consistent with physiologically relevant CT receptors in other systems. For the determination of CT binding in the human medulla, 20-micron cryostat sections were incubated with 125I-salmon CT in the presence or absence of 10(-6) M unlabelled salmon CT to map specific CT binding sites. Punctate binding was observed over discrete nuclei of the medulla. High binding densities were seen over subnuclei of the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the intermediate reticular zone, the gigantocellular and dorsal paragigantocellular nuclei, and the raphe obscurus nucleus. Moderate levels of binding were observed over the lateral paragigantocellular nucleus and the rostral extent of the epiolivary nucleus. The cuneate and gracile nuclei and the fiber tracts did not contain detectable binding, while the inferior olivary nucleus had moderate levels of nonspecific binding. The localization of calcitonin binding sites in the human presents similarities but also important differences to the distribution in rat and cat. The most notable difference is the extreme binding densities in the intermediate reticular zone of the human. The location of binding sites suggests involvement of calcitonin in regulation of autonomic function.

Aged↗

PubMed1994

In vitro autoradiographic localization of amylin binding sites in rat brain.

Amylin is a recently discovered 37 amino acid peptide which is co-secreted from the pancreas with insulin and acts to modulate carbohydrate metabolism. Recently, high-affinity binding sites for [125I]rat amylin have been identified in the rat central nervous system. These sites also have high affinity for the structurally related peptides calcitonin gene-related peptide and salmon calcitonin. In the present study we have used in vitro autoradiography to map the distribution of these [125I]rat amylin binding sites in rat brain. High to moderate levels of binding were present in mid-caudal accumbens nucleus, fundus striati and parts of the bed nucleus of the stria terminalis and substantia inominata. This binding extended caudally into parts of the amygdalostriatal transition zone and the central and medial amygdaloid nuclei. High to moderate levels of binding also occurred in much of the hypothalamus including the medial preoptic, dorsomedial hypothalamic and medial tuberal nuclei as well as the ventrolateral subnucleus of the ventromedial hypothalamic nucleus. Other regions of high level binding included the subfornical organ, the vascular organ of the lamina terminalis, area postrema, locus coeruleus, dorsal raphe and caudal parts of the nucleus of the solitary tract. The subfornical organ, vascular organ of the lamina terminalis and area postrema, which display some of the highest binding densities, lack a patent blood-brain barrier and thus could be responsive to blood-borne amylin. In conclusion we have mapped, in detail, the distribution of amylin binding sites in rat brain. The location of binding is consistent with potential roles for these sites in appetite, fluid and electrolyte homeostasis, autonomic function and regulation of mood.

Amyloid↗

PubMed1993

Substance P- and tyrosine hydroxylase-containing neurons in the human dorsal motor nucleus of the vagus nerve.

The aim of this study was to provide a comprehensive account of the topography, morphology, and frequencies of the substance P- and tyrosine hydroxylase-containing neurons in the human dorsal motor nucleus of the vagus nerve. The morphology of immunoreactive neurons was studied and the variations of the cell distributions were presented by three-dimensional computer reconstructions. Three types of substance P-like immunoreactive neurons were identified. They were predominantly located in the dorsointermediate, centrointermediate, caudointermediate, and caudal division of the dorsal motor nucleus of the vagus nerve. The morphology of substance P-like immunoreactive neurons varied according to the subnuclei in which they were found. Three types of tyrosine hydroxylase-like immunoreactive neurons were identified, mainly in the periphery of the dorsal motor nucleus of the vagus nerve, including the medial fringe, ventrointermediate, and dorsointermediate subnuclei of the 10. Many cells throughout the ventrointermediate subnucleus of the dorsal motor nucleus of the vagus nerve are seen ventrally to intermingle with the tyrosine hydroxylase neurons of the intermediate reticular zone. Computer reconstructions provided a three-dimensional view of the positions of substance P- and tyrosine hydroxylase-like immunoreactive neurons within the subdivisions of the dorsal motor nucleus of the vagus nerve. The uneven distribution of substance P- and tyrosine hydroxylase-like immunoreactive neurons within the subdivisions suggests an involvement of these substances in some, but not all, autonomic functions of the dorsal motor nucleus of the vagus nerve.

Aged↗

PubMed1993

Dorsal motor nucleus of the vagus nerve: a cyto- and chemoarchitectonic study in the human.

In order to investigate the topography and subdivisions of the human dorsal motor nucleus of the vagus nerve (10), studies were conducted using cyto- and chemoarchitectonic (acetylcholinesterase and substance P-like immunoreactivity) and computer reconstruction techniques. The six brainstems examined were obtained within 17 hours postmortem from adults with no known neurological disorders. Serial sections cut in transverse, sagittal, and coronal planes were stained with cresyl violet, or tested for acetylcholinesterase or substance P. The neurons of the 10 (16,826 +/- 967) displayed cyto- and chemoarchitectonic heterogeneity and could be classified into six types. Types I-V consist of presumed vagal motor neurons (13,802 +/- 844), while the remaining type (Type VI) consisted of presumed interneurons (3,024 +/- 769). The 10 was subdivided into nine subnuclei grouped regionally into rostral, intermediate, and caudal divisions on the basis of neuronal morphology, cell density, and differential AChE and substance P reactivities. The rostral division contains the dorsorostral (DoR) and the ventrorostral (VeR) subnuclei; the intermediate division contains the rostrointermediate (RoI), dorsointermediate (DoI), centrointermediate (CeI), ventrointermediate (VeI), and caudointermediate (CaI) subnuclei; the caudal division (Ca) is not subdivided. Morphologically, small round or oval cells populate the VeR and VeI. Medium-sized oval cells occur in the DoR, CeI, and Ca, while medium-sized fusiform and multipolar cells are the main features of CaI. Large triangular cells appear mainly in DoI. Glial cells show the highest predilection for CeI, lowest densities in DoI and medial fringe subnucleus (MeF), and intermediate densities in the remaining six subnuclei. VeI showed the strongest AChE reactivity. Although the cell bodies of VeR and DoI are AChE positive, the neuropil (background) is weakly stained. Densely distributed fine granular substance P-like immunoreactivity occurs throughout the entire nucleus, while the intermediate and caudal divisions contain substance P-like-immunoreactive neurons. Three-dimensional computer reconstructions afforded an appreciation of the distinctiveness of the intermediate division (a division that contains the majority of cells) and the caudal division, which displays the lowest density of presumed vagal motoneurons. It is possible that the subnuclei identified herein form functional units innervating specific organs.

Acetylcholinesterase↗

PubMed1993

Dopa resistance in multiple-system atrophy: loss of postsynaptic D2 receptors.

Postmortem autoradiography was used to explore the mechanisms underlying L-dopa resistance in 2 patients with multiple-system atrophy. Indices of striatal presynaptic dopamine terminal loss and dopamine (D1 and D2) receptors were provided by 3H-mazindol, 3H-SCH 23390, and 125I-sulpiride binding. Neuronal loss, gliosis, and loss of postsynaptic D2 receptors preferentially involved the middle and posterior of the putamen, that region of the striatum most intimately involved in motor function. Loss of D1 receptors in the same area occurred in only 1 patient. These findings suggest that in multiple-system atrophy, resistance to L-dopa is due to a loss of putamental D2 receptors. The differential effects on D1 and D2 receptors in 1 patient implies that different subpopulations of striatal neurons were selectively involved.

Aged↗

PubMed1992

Localization of preprogalanin mRNA in the monkey hippocampal formation.

The existence of neurons expressing preprogalanin mRNA in the monkey hippocampal formation was demonstrated using in situ hybridization of a radio-labelled cRNA probe transcribed from human preprogalanin cDNA. Specific hybridization occurred in neurons of the hilus of the dentate gyrus, fields CA1-3 in Ammon's horn, subiculum, presubiculum, parasubiculum and occasionally in neurons of the entorhinal cortex. These findings suggest that galanin is synthesized by neurons intrinsic to the monkey hippocampal formation.

Animals↗

PubMed1992

The dorsal, posterodorsal, and ventral tegmental nuclei: a cyto- and chemoarchitectonic study in the human.

In order to verify the existence of the ventral and posterodorsal tegmental nuclei and to extend previous findings regarding the dorsal tegmental nucleus in the human brainstem, studies were conducted using cyto- and chemoarchitectonics, and computer reconstruction techniques. Serial sections of five brainstems from adults with no known neurological disorders were stained for Nissl substance, acetylcholinesterase, and substance P. The topography, cytoarchitecture, and acetylcholinesterase reactivity of the tegmental nuclei were presented in a mini-atlas depicting sections cut in transverse and sagittal planes. The dorsal and posterodorsal tegmental nuclei were identified fully within the central grey matter while the ventral tegmental nucleus extended across the medial longitudinal fasciculus into the pontine reticular formation. The dorsal tegmental nucleus featured a cell-poor pericentral part, strongly positive for acetylcholinesterase, and a central part comprised of densely packed small neurons that displayed moderate acetylcholinesterase reactivity and strong substance P-like immunoreactivity. The posterodorsal tegmental nucleus, located in the same transverse plane as the rostral part of the motor nucleus of the trigeminal nerve, was composed of diffusely arranged small to medium neurons with its neuropil displaying moderate acetylcholinesterase reactivity and strong substance P-like immunoreactivity. The ventral tegmental nucleus, identified as a prominent structure in the pontine tegmentum immediately rostral to the genu of the facial nerve, contained predominantly large neurons and displayed intensive acetylcholinesterase reactivity and substance P-like immunoreactivity. These studies showed that the tegmental nuclei, which displayed distinctive cyto- and chemoarchitectonic features, were fully present in adult human brainstem.

Acetylcholinesterase↗

PubMed1992

Mapping of angiotensin II receptor subtype heterogeneity in rat brain.

Angiotensin II (Ang II) exerts a number of central actions on fluid and electrolyte homeostasis, autonomic activity, and neuroendocrine regulation. In order to evaluate likely sites where these actions are mediated, Ang II receptor binding was localized in rat brain by in vitro autoradiography with the aid of the antagonist analogue 125I-[Sar1, Ile8]Ang II. Two subtypes of Ang II receptor have been identified using recently developed peptide and nonpeptide antagonists. In the periphery, the receptor subtypes differ in distribution, second messenger coupling, and function. Brain Ang II receptor subtypes were therefore differentiated into AT-1 (type I) and AT-2 (type II) subtypes by using unlabelled nonpeptide antagonists specific for the two Ang II subtypes. AT-1 binding was determined to be that inhibited by Dup 753 (10 microM) and AT-2 binding to be that inhibited by PD 123177 (10 microM). The reducing agent dithiothreitol (DTT) decreased binding to AT-1 receptors and enhanced binding to AT-2 receptors. Many brain structures, such as the vascular organ of the lamina terminalis, subfornical organ, median preoptic nucleus, area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, which are known to be related to the central actions of Ang II, contain exclusively AT-1 Ang II receptors. By contrast, the locus coeruleus, ventral and dorsal parts of lateral septum, superior colliculus and subthalamic nucleus, many nuclei of the thalamus, and nuclei of the inferior olive contain predominantly AT-2 Ang II receptors. The detailed binding characteristics of each subtype were determined by competition studies with a series of analogues of angiotensin and antagonists. The pharmacological specificity obtained in rat superior colliculus and the nucleus of the solitary tract agreed well with published data on AT-1 and AT-2 receptors, respectively. There was a high degree of correlation between the distribution of Ang II binding sites with published data on Ang II-immunoreactive fields and on the sites of Ang II-responsive neurons. The present study also reveals pharmacological heterogeneity of brain Ang II receptors. The subtype-specific receptor mapping described here is relevant to understanding the role of angiotensin peptides in the central nervous system and newly discovered central actions of nonpeptide Ang II receptor antagonists.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1992

Effects of an infusion of morphine into the accumbens nucleus upon acquisition of hypoalgesic and fear responses in rats exposed to a heart stressor.

Four experiments examined the effects of an infusion of morphine into the accumbens nucleus upon the aversive conditioning that can occur in rats exposed to the heated floor of a hot-plate apparatus. An infusion of morphine into the accumbens nucleus but not into the caudoputamen or into the prefrontal cortex impaired the acquisition of a conditioned hypoalgesic (Experiment 1) and fear (Experiment 4) response. This impairment was dose-dependent (Experiment 2) and mediated by opioid receptors in the accumbens nucleus, because it was removed by a systemic (Experiment 3a) or by an accumbal (Experiment 3b) infusion of naloxone. The results were attributed to an antagonism between the reinforcement process for aversive conditioning and the appetitive properties of an accumbal infusion of morphine.

Analgesia↗

PubMed1991

Localization and characterization of angiotensin II receptor binding sites in the human basal ganglia, thalamus, midbrain pons, and cerebellum.

Angiotensin II (Ang II) binding sites were localized in the thalamus, basal ganglia, midbrain, and pons of the human central nervous system by in vitro autoradiography, employing 125I-[Sar1, Ile8]angiotensin II as the radioligand. High-density binding occurs in the substantia nigra pars compacta, the interpeduncular nucleus and two of the raphe nuclei, the raphe magnus, and median raphe nucleus. Moderate densities occur in the caudate nucleus, putamen, bed nucleus of the stria terminalis, rostral linear nucleus, caudal linear nucleus, dorsal and paramedian raphe nuclei, locus coeruleus, and region of the subcoeruleus, oral dorsal paramedian nucleus, and A5/periolivary region. Low levels occur in the region between the subthalamic nucleus and the zona incerta, the mediodorsal thalamic nucleus, the central gray, the lateral and medial parabrachial nuclei, and the molecular layer of the cerebellum. The high density of Ang II receptor binding in the substantia nigra occurs over pigmented, presumably dopaminergic, neurons. The binding in this site, and in the striatum, is not observed in any of the other species we have studied. It displays similar pharmacological characteristics to the Ang II receptor binding site in other regions of the human brain. Overall we demonstrate a discrete pattern of Ang II receptor binding sites in the human brain, which shows a high correlation with the distribution observed in other mammalian species.

1-Sarcosine-8-Isoleucine Angiotensin II↗