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A Parent

Publications and source records attributed to A Parent.

At least 73 records · Page 4Linked to original sources

Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates: Phaseolus vulgaris-leucoagglutinin anterograde labeling combined with postembedding glutamate and GABA immunohistochemistry.

To verify the possibility that the pedunculopontine nucleus is a source of glutamatergic terminals in contact with midbrain dopaminergic neurons in the squirrel monkey, we used the anterograde transport of Phaseolus vulgaris-leucoagglutinin in combination with preembedding immunohistochemistry for tyrosine hydroxylase and for calbindin D-28k and postembedding immunocytochemistry for glutamate and for gamma-aminobutyric acid. Following tracer injections in the pedunculopontine nucleus, numerous anterogradely labeled fibers emerged from the injection sites to innervate densely the pars compacta of the substantia nigra and ventral tegmental area. The major type of labeled fibers were thin with multiple collaterals and varicosities that established intimate contacts with midbrain dopaminergic neurons. At the electron microscopic level, the anterogradely labeled boutons were medium sized (maximum diameter between 0.9 microns and 2.5 microns) and contained numerous round vesicles and mitochondria. Postembedding immunocytochemistry revealed that 40-60% of anterogradely labeled terminals were enriched in glutamate and formed asymmetric synapses with dendritic shafts of substantia nigra and ventral tegmental area neurons. In triple-immunostained sections, some of the postsynaptic targets to these terminals were found to be dopaminergic. In addition, 30-40% of the anterogradely labeled terminals in both regions displayed immunoreactivity for gamma-aminobutyric acid and, in some cases, formed symmetric synapses with dendritic shafts. In conclusion, our results provide the first ultrastructural evidence for the existence of synaptic contacts between glutamate-enriched terminals from the pedunculopontine nucleus and midbrain dopaminergic neurons in primates. Our results also show that the pedunculopontine nucleus is a potential source of gamma-aminobutyric acid input to this region. These findings suggest that the pedunculopontine nucleus may play an important role in the modulation of the activity of midbrain dopaminergic cells by releasing glutamate or gamma-aminobutyric acid as neurotransmitter.

Animals↗

Limbic system-associated membrane protein (LAMP) in primate amygdala and hippocampus.

The distribution of the limbic system-associated membrane protein in the amygdaloid complex and hippocampal formation of cynomolgus monkeys (Macaca fascicularis) was studied with immunohistochemical procedures. A highly complex and heterogeneous staining pattern is encountered in the macaque amygdala. The basal, lateral, and accessory basal nuclei display the most intense immunostaining with local heterogeneities. The lateral division of the central nucleus also stains intensely, whereas the medial division of the central nucleus and the medial nucleus are more weakly stained. The dorsal division of the bed nucleus-amygdala continuum (extended amygdala) is strongly immunoreactive. The hippocampus displays the strongest immunoreactivity encountered so far in the primate brain. The intensity of the immunostaining is highest in the cornu Ammonis (Ammon's horn; CA1-CA3 fields) and gradually decreases toward the dentate gyrus or the subicular area. In the hippocampus proper, the stratum radiatum, the pyramidal layer, the stratum oriens, and the alveus all display intense immunoreactivity. The immunostaining is much less prominent in the dentate gyrus, whose granule cell layer is completely devoid of labeling. In the subicular area, there is a lateromedial decreasing gradient in immunostaining intensity, the subiculum being moderately stained and the parasubiculum weakly stained. These results reveal that the limbic system-associated membrane protein labels structures that form the core of the limbic system in primates. Within each of these structures, however, the labeling is highly heterogeneous and appears to be confined to specific functional domains.

Amygdala↗

Striatal interneurons in Huntington's disease: selective increase in the density of calretinin-immunoreactive medium-sized neurons.

The marked atrophy of the striatum seen in Huntington's disease (HD) is largely due to a massive neuronal loss that affects the striatal projection neurons more severely than the local circuit neurons. We recently reported the existence of a new class of interneurons characterized by their immunoreactivity for the calcium-binding protein calretinin in the human striatum. In the present immunohistochemical study, we compared the distribution and relative density of the calretinin-expressing interneurons in the striata of four normal individuals and four patients with HD (grade 1 to 3). The population of calretinin-containing interneurons comprised (a) a small subset of large (17- to 44-microns), multipolar neurons with five to seven long, aspiny, and highly branched dendrites and (b) a large number of medium-sized (8- to 18-microns), round-to-oval neurons with two to three long, varicose, and poorly branched dendrites. Both types of chemospecific neurons occurred throughout the striatum in all specimens examined, but the density of the medium-sized neurons was much higher in patients with HD than in controls. A quantitative analysis showed a significant (p < 0.01) twofold increase in the density of the striatal medium-sized neurons and a similar decrease in the density of the large neurons in patients with HD compared with controls. This differential effect on the densities of the two types of interneurons suggests that calretinin may protect the medium-sized but not the large neurons against neurodegeneration in HD.

Adult↗

Calcium-binding proteins in primate basal ganglia.

This paper describes the distribution of the calcium-binding proteins calbindin-D28k. Parvalbumin and calretinin in primate basal ganglia. The data derive from immunocytochemical studies undertaken in squirrel monkeys (Saimiri sciureus) and in normal human individuals. In the striatum, calbindin labels medium-sized spiny projection neurons whereas parvalbumin and calretinin mark two separate classes of aspiny interneurons. The striatal matrix compartment is markedly enriched with calbindin while striatal patches (striosomes) display a calretinin-rich neuropil. In the pallidum, virtually all neurons contain parvalbumin but none express calbindin. Calretinin occurs only in a small subpopulation of both large and small pallidal neurons. In the subthalamic nucleus, there exists a multitude of parvalbumun-positive cells and fibers but the number of calretinin and calbindin-positive neuronal elements is small. In the substantia nigra/ventral tegmental area complex, calbindin and calretinin occur principally in dopaminergic neurons of the dorsal tier of the pars compacta and in those of the ventral tegmental area. Parvalbumin is strictly confined to the GABAergic neurons of the pars reticulata and lateralis. Calbindin-rich fibers abound in the pars reticulata and lateralis, while calretinin-positive axons are confined to the pars compacta. These results indicate that calbindin and parvalbumin are distributed according to a strikingly complementary pattern in primate basal ganglia. Calretinin is less ubiquitous but occurs in all basal ganglia components where it labels distinct subsets of neurons. Such highly specific patterns of distribution indicate that calbindin, parvalbumin and calretinin may work in synergy within primate basal ganglia.

Animals↗

Striatal and cortical projections of single neurons from the central lateral thalamic nucleus in the rat.

Striatal and cortical projections arising from the central lateral thalamic nucleus were studied in rats by tracing the axons of small pools of neurons labeled anterogradely with biocytin. Cells of the central lateral nucleus have a morphology that conforms to the classic descriptions of the bushy cells which represent the main neuronal type of most thalamic nuclei. They display many short radiating dendrites studded with sessile spines, protrusions and grapelike appendages. The total extent of their dendritic fields is about 250 mu m. After leaving the nucleus, all central lateral axons course through the rostrolateral pole of the thalamic reticular nucleus, where they branch profusely, enter the striatum, where they distribute collaterals, and arborize in the motor cortex. At striatal level, central lateral fibers form a loosely organized network composed of varicose axonal branches that appear to contact en passant several striatal neurons. In the cortex. central lateral axons from multiple (four to five patches of terminations in layers Va and III aligned along the rostrocaudal extent of the motor area. The projection to layers I and II is very sparse, consisting of occasional branches which show few ramifications. Our results indicate that most, and perhaps all, central lateral relay neurons project to both the striatum and cerebral cortex. The patchy innervation of mid cortical layers of the frontal motor areas by central lateral afferents strongly argues against the nonspecific character of this projection. It is proposed that the central lateral nucleus, which receives a strong innervation from brainstem cholinergic afferents, takes part in a mechanism of attention related to the central initiation of directed patterns of movements.

Animals↗

Calretinin immunoreactivity in the thalamus of the squirrel monkey.

The distribution of the calcium-binding protein, calretinin, in the thalamus of the squirrel monkey (Saimiri sciureus) was studied with immunohistochemical methods. Calretinin was found to be heterogeneously distributed in the primate thalamus and to occur only in specific neuronal populations of certain thalamic nuclei. Neuronal cells and fibers in midline nuclei and their dorsolateral extension, which includes the parataenial and central superior lateral nuclei, displayed the most intense calretinin immunoreactivity. The immunoreactivity for cells and fibers in the intralaminar nuclei was moderate rostrally but very weak caudally. The centre mèdian nucleus, together with the medial habenular nucleus, were virtually devoid of calretinine immunostaining. The mediodorsal nucleus displayed a markedly heterogeneous staining, with numerous clusters of labeled cells and fibers in its central parvicellular part. Cell and fiber immunoreactivity ranged from moderate to high in the nuclei of the anterior and lateral groups, but was very weak in the nuclei of the ventral and posterior groups. There was a small to moderate number of heterogeneously distributed calretinin-immunoreactive cells and fibers in the lateral and medial geniculate bodies, as well as in the reticular nucleus. The present study provides the first evidence for the existence of calretinin in primate thalamus, where this protein is distributed according to a highly heterogeneous pattern. This specific pattern of distribution suggests that calretlnin may play a role that is complementary to those of the other calcium-binding proteins parvalbumin and calbindin D-28k in the thalamus of primates.

Animals↗

Determination of oenothein B as the active 5-alpha-reductase-inhibiting principle of the folk medicine Epilobium parviflorum.

Several extracts from Epilobium parviflorum, a plant used in Central Europe for the treatment of prostate disorders, were evaluated in a biochemical assay with 5-alpha-reductase. The aqueous extract displaying inhibition of the enzyme was analyzed, the fraction responsible for this activity was purified, and the active compound identified as a macrocyclic tannin, oenothein B (1).

5-alpha Reductase Inhibitors↗

Total liquid ventilation with perfluorocarbons increases pulmonary end-expiratory volume and compliance in the setting of lung atelectasis.

OBJECTIVE: To compare compliance and end-expiratory lung volume during reexpansion of normal and surfactant-deficient ex vivo atelectatic lungs with either gas or total liquid ventilation. DESIGN: Controlled, animal study using an ex vivo lung preparation. SETTING: A research laboratory at a university medical center. SUBJECTS: Thirty-six adult cats, weighing 2.5 to 4.0 kg. INTERVENTIONS: Heparin (300 U/kg) was administered, cats were killed, and lungs were excised en bloc. Normal lungs and saline-lavaged, surfactant-deficient lungs were allowed to passively collapse and remain atelectatic for 1 hr. Lungs then were placed in a plethysmograph and ventilated for 2 hrs with standardized volumes of either room air or perfluorocarbon. Static pulmonary compliance and end-expiratory lung volume were measured every 30 mins. MEASUREMENTS AND MAIN RESULTS: Reexpansion of normal atelectatic lungs with total liquid ventilation was associated with an 11-fold increase in end-expiratory lung volume when compared with the increase in end-expiratory lung volume observed with gas ventilation (total liquid ventilation 50 +/- 14 mL, gas ventilation 4 +/- 9 mL, p < .0001). The difference was even more pronounced in the surfactant-deficient lungs with an approximately 19-fold increase in end-expiratory lung volume observed in the total liquid ventilated group, compared with the gas ventilated group (total liquid ventilation 44 +/- 17 mL, gas ventilation 2 +/- 8 mL, p = .0001). Total liquid ventilation was associated with an increase in pulmonary compliance when compared with gas ventilation in both normal and surfactant-deficient lungs (normal: gas ventilation 6 +/- 1 mL/cm H2O, total liquid ventilation 14 +/- 4 mL/cm H2O, p < .0001; surfactant-deficient: gas ventilation 4 +/- 1 mL/cm H2O, total liquid ventilation 9 +/- 3 mL/cm H2O, p < .01). CONCLUSIONS: End-expiratory lung volume and static compliance are increased significantly following attempted reexpansion with total liquid ventilation when compared with gas ventilation in normal and surfactant-deficient, atelectatic lungs. The ability of total liquid ventilation to enhance recruitment of atelectatic lung regions may be an important means by which gas exchange is improved during total liquid ventilation when compared with gas ventilation in the setting of respiratory failure.

Animals↗

Evaluation of gas exchange, pulmonary compliance, and lung injury during total and partial liquid ventilation in the acute respiratory distress syndrome.

OBJECTIVE: To investigate whether pulmonary compliance and gas exchange will be sustained during "total" perfluorocarbon liquid ventilation followed by "partial" perfluorocarbon liquid ventilation when compared with gas ventilation in the setting of the acute respiratory distress syndrome (ARDS). STUDY DESIGN: A prospective, controlled, laboratory study. SETTING: A university research laboratory. SUBJECTS: Ten sheep, weighing 12.7 to 25.0 kg. INTERVENTIONS: Lung injury was induced in ten young sheep, utilizing a right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage. Bijugular venovenous extracorporeal life support access, a pulmonary artery catheter, and a carotid artery catheter were placed. When the alveolar-arterial O2 gradient was >/= 600 torr and PaO2 </= 50 torr (</= 6.7 kPa) with an FIO2 of 1.0, extracorporeal life support was instituted. For the first 30 mins on extracorporeal life support, all animals were ventilated with gas. Animals were then ventilated with equal tidal volumes of 15 mL/kg during gas ventilation (n=5) over the ensuing 2.5 hrs, or with total liquid ventilation for 1 hr, followed by partial liquid ventilation for 1.5 hrs (total/partial liquid ventilation, n=5). MEASUREMENTS AND MAIN RESULTS: An increase in physiologic shunt (gas ventilation = 69 +/- 11%, total/partial liquid ventilation = 71 +/- 3%) and a decrease in static total pulmonary compliance measured at 20 mL/kg inflation volume (gas ventilation = O.48 +/- 0.03 mL/cm H2O/kg, total/partial liquid ventilation = 0.50 +/- 0.17 mL/cm H2O/kg) were observed in both groups with induction of lung injury. Physiologic shunt was significantly reduced during total and partial liquid ventilation when compared with physiologic shunt observed in the gas ventilation animals (gas ventilation = 93 +/- 8%, total liquid ventilation = 45 +/- 11%, p<.001; gas ventilation = 95 +/- 3%, partial liquid ventilation = 61 +/- 12%, p<.001), while static compliance was significantly increased in the total, but not the partial liquid ventilated animals when compared with the gas ventilated group (gas ventilation = 0.43 +/- 0.03 mL/cm H2O/kg, total liquid ventilation = 1.13 +/- 18 mL/cm H2O/kg, p <.001; gas ventilation = 0.41 +/- 0.02 mL/cm H2O/kg, partial liquid ventilation = 0.47 +/- 0.08, p = .151). In addition, the extracorporeal life support flow rate required to maintain adequate oxygenation was significantly lower in the total/partial liquid ventilation group when compared with that of the gas ventilation group (gas ventilation = 89 +/- 7 mL/kg/min, total liquid ventilation = 22 +/- 10 mL/kg/min, p <.001; gas ventilation = 91 +/- 12 mL/kg/min, partial liquid ventilation = 41 +/- 11 mL/kg/min, p < .001). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the total/partial liquid ventilation animals when compared with the gas ventilation animals. CONCLUSIONS: In a model of severe ARDS, pulmonary gas exchange is improved during total followed by partial liquid ventilation. Pulmonary compliance is improved during total, but not during partial liquid ventilation. Total followed by partial liquid ventilation was associated with a reduction in alveolar hemorrhage, pulmonary edema, and lung inflammatory infiltration.

Animals↗

A single-cell study of the axonal projections arising from the posterior intralaminar thalamic nuclei in the rat.

Thalamostriatal projections arising from the posterior intralaminar nuclei (P1; the parafascicular nucleus and the adjacent caudalmost part of the posterior thalamic group) were studied in rats by tracing the axons of small pools of neurons labelled anterogradely with biocytin. Thirteen P1 cells were also stained by juxta cellular application of the tracer. Relay cells of P1 nuclei have a morphology that differs radically from the classical descriptions of the bushy cells which represent the main neuronal type of the sensory thalamic relay nuclei. P1 cells have ovoid or polygonal somata of approximately 20-25 microm, from which emerge four or five thick, long and poorly branched dendrites bearing spines and filamentous appendages; their dendritic domains extend for up to 1.5 mm. Before leaving the nucleus 20% of axons give off collaterals that ramify locally. All axons course through the thalamic reticular nucleus, where they also distribute collaterals, and arborize massively in the striatum and sparsely in the cerebral cortex. At the striatal level four or five collaterals leave the main axon and terminate in patches scattered dorsoventrally within a rostrocaudally oriented slab. As revealed by calbindin D-28k immunohistochemistry, only the matrix compartment receives terminations from P1 axons. The cortical branch form small terminal puffs centred upon layer VI of the motor cortex. Before entering the striatum some axons of the parafascicular nucleus give rise to descending collaterals that arborize in the entopeduncular nucleus, in the subthalamic nucleus and in the vicinity of the red nucleus. Other axons arising from the caudal part of the posterior group send descending branches only to the entopeduncular nucleus. These findings show that P1 cells belong to a distinct category of thalamic relay neurons which, beside their massive projection to the striatum, also distribute collaterals to other components of the basal ganglia. Moreover, these results provide the first direct evidence that virtually all P1 cells project to both striatum and cerebral cortex. Finally, it is proposed on the basis of morphological, histochemical and hodological criteria that the caudal part of the posterior thalamic group in the rat is homologous to the suprageniculate-limitans nuclei of cats and primates.

Afferent Pathways↗

Two different types of thalamic fibers innervate the rat striatum.

Thalamostriatal projections were studied in rats by tracing the axons of small pools of thalamic neurons labeled anterogradely with biocytin. Single-cell mapping of these projections revealed two types of thalamostriatal fibers. The first type arises from the bushy relay cells of the central lateral and associative thalamic nuclei which arborize sparsely in the striatum by means of long varicose axon collaterals. The second type of fiber arises from large, reticular-like, relay cells located in the parafascicular and ethmoid nuclei. These latter fibers form dense clusters of terminations within the striatum and they also send branches to other components of the basal ganglia. These different morphological features suggest that the two types of fibers subserve different functions.

Animals↗

Single striatofugal axons arborizing in both pallidal segments and in the substantia nigra in primates.

The striatofugal fiber system in primates is believed to be composed of separate subsystems terminating in either the external (GPe) or internal (GPi) segment of the globus pallidus, or in the substantia nigra (SN). At variance with this concept is the present demonstration of single biocytin-labeled striatofugal axons that arborize in the three major target structures of the striatum in cynomolgus monkeys. Out of nine single-labeled axons that were analyzed in detail, one terminated exclusively in GPc, another in both GPc and GPi, whereas the rest arborized in GPe, GPi and SN. The axons that branched in the three sites had one preferential recipient structure where they arborized profusely and formed typical woolly fibers. These findings suggest that, in contrast to previous beliefs based on results of retrograde double-labeling studies, most striatofugal axons arborize within more than one striatal target structures in primates.

Animals↗

Heterogeneous distribution of neurons containing calbindin D-28k and/or parvalbumin in the rat red nucleus.

The cellular localization of calbindin D-28k (CB) and parvalbumin (PV) in the red nucleus of the rat was studied by means of double-immunohistochemical techniques applied to single sections. Neurons displaying immunoreactivity for either CB or PV were found throughout the rostrocaudal extent of the red nucleus, but PV neurons predominate in the rostral two-thirds and CB neurons in the caudal two-thirds of the nucleus. Likewise, there was a clear but not absolute segregation of the two types of neurons along the dorsoventral axis; PV and CB neurons were largely confined to the dorsolateral and ventromedial sectors of the nucleus, respectively. Most CB neurons were large (> 30 microns), whereas large and medium-sized (15-30 microns) PV neurons were equally abundant. Additionally, some large and medium-sized neurons displaying immunoreactivity for both PV and CB were encountered in the ventromedial sector of the red nucleus. The present study reveals that, in contrast to previous beliefs, the red nucleus is composed of a neuronal population that is chemically highly heterogeneous.

Animals↗

[3H]phorbol 12,13-dibutyrate/PKC binding in thoracic spinal cord: no change in amyotrophic lateral sclerosis.

[3H]phorbol 12,13-dibutyrate ([3H]PDBu), a selective ligand for various protein kinase C isozymes (PKC), was used to investigate the distribution of [3H]PDBu/PKC binding sites in thoracic spinal cords of patients who died with amyotrophic lateral sclerosis (ALS) and subjects free of neurological disease. In controls, binding of [3H]PDBu was mostly concentrated in the substantia gelatinosa and to a lesser extent in other dorsal horn regions (laminae III and IV). [3H]PDBu binding sites were also present in the ventral horn and laminae X but in somewhat lower quantities. The distribution of [3H]PDBu binding in thoracic spinal cords of patients who died with ALS was unchanged compared to controls and no significant differences were observed in the amount of specific binding in ALS. The present results on the distribution of [3H]PDBu binding sites in human spinal cord are consistent with previous studies of [3H]PDBu binding in rodents indicating that high levels of PKC are present in the dorsal horn. The results also suggest that levels of PKC isozymes are not altered in ALS spinal cord.

Aged↗

The thalamic reticular nucleus does not send commissural projection to the contralateral parafascicular nucleus in the rat.

The reticular nucleus of the thalamus (NRT) projects to virtually all thalamic nuclei ipsilaterally. In addition, recent studies suggest that NRT sends contralateral projections through an intrathalamic commissural fiber system to several thalamic nuclei, including the NRT itself. In the present study we used retrograde cell labeling, multi-unit anterograde labeling and immunohistochemical methods to study both ipsi- and contralateral NRT projection to the parafascicular nucleus (Pf) in the rat. Injections of the fluorescent tracers true blue or fluorogold in Pf led to massive retrograde cell labeling in rostral and dorsal portions of the ipsilateral NRT, whereas the same sectors of the contralateral NRT were devoid of labeling. Some retrogradely labeled cells were nevertheless present on the contralateral side in the borderline region between NRT and the zona incerta (ZI). Retrograde cell labeling experiments with cholera toxin B subunit (CTb) combined to immunohistochemistry for parvalbumin (PV) and calbindin D-28k (CB) indicated that the few retrogradely labeled cells encountered at the border between NRT and ZI displayed immunoreactivity for CB but not for PV. Since PV and CB label neurons belonging to NRT and ZI, respectively, it is concluded that these contralateral retrogradely labeled cells belong to ZI and not to NRT. Multi-unit cell anterograde labeling experiments with biocytin showed that NRT cells that project to Pf arborize extensively only on the ipsilateral side. The same approach, however, has revealed NRT cells projecting to both ipsi- and contralateral ventromedial thalamic nuclei. The axon of these NRT neurons arborizes more profusely ipsilaterally than contralaterally. These results reveal that the NRT projection to Pf in rodents is strictly unilateral. These findings are at variance with the emerging concept that NRT exerts a prominent bilateral influence upon most thalamic nuclei.

Animals↗

Striatal neurones displaying substance P (NK1) receptor immunoreactivity in human and non-human primates.

The striatum of normal human subjects and that of squirrel monkeys (Saimiri sciureus) was found to contain two distinct types of neurones displaying immunoreactivity for substance P (neurokinin-1) receptor (SPR). Large and medium-sized SPR-immunoreactive neurones, both with aspiny dendrites, were fairly uniformly distributed in the striatum of humans and squirrel monkeys. In humans the proportions of large and medium-sized SPR-positive neurones were 57.2% and 42.8% in putamen, compared with 51.9% and 48.1% in caudate nucleus. These findings suggest that substance P exerts its local influence not only on large cholinergic neurones, as commonly believed, but also on a subset of medium-sized interneurones in the striatum of human and non-human primates.

Adult↗

Calretinin-immunoreactive neurons in the human striatum.

The human striatum contains two types of neurons displaying immunoreactivity for the calcium-binding protein calretinin (CR): (1) large (22, 44 microns>), multipolar neurons with 5-7 long, aspiny and tightly branched dendrites, and (2) medium-sized (9-18 microns), round-to-oval neurons with 2-3 long, varicose and poorly branched dendrites. These CR neurons represent only a small proportion of the total neuronal population and they are heterogeneously distributed in the striatum. The large CR neurons are more numerous in the putamen than in the caudate nucleus, whereas the inverse is true for the medium-sized CR neurons. The ratio of large- to medium-size CR neurons is 1:4 in the putamen compared to 1:6 in the caudate nucleus. The existence of these two distinct subsets of chemospecific striatal neurons suggest that CR may play an important role in the intrinsic organization of the human striatum.

Adult↗