Keiji Satoh

Divergent projections of catecholamine neurons of the locus coeruleus as revealed by fluorescent retrograde double labeling technique

Divergent projections of catecholamine (CA) neurons of the locus coeruleus have been studied by fluorescent retrograde double labeling in conjunction with monoamine histofluorescence technique. The present results indicate that the coerulo-cortical CA system is composed of two types of neurons. A predominant type possesses few divergent axons innervating a restricted region, while the other type projects widely to various areas of the cerebral cortex. The existence of divergent axonal projections of single CA neurons in the locus coeruleus to the cerebellum and the spinal cord, to the frontal cortex and the cerebellum, is also demonstrated.

Neurochemical heterogeneity of the primate nucleus accumbens.

In order to further investigate the neurochemical anatomy of the primate nucleus accumbens (NAC), the distributions of the neuropeptides leucine-enkephalin (Leu-ENK), neurotensin (NT), and substance P (SP) and of haloperidol-induced c-fos expression were investigated in the macaque monkey using immunohistochemical methods. To define the boundaries of the NAC, dopamine (DA) and tyrosine hydroxylase (TH) immunohistochemistry was performed. In addition, to formulate the distinction between subdivisions of the nucleus accumbens, immunohistochemistry for calbindin-D28 (CBD) and SP was employed. In general, the medial part of NAC, which consisted of small to medium-sized cells, was low for CBD immunoreactivity and moderate to high for SP immunoreactivities, while the dorsolateral part, which was composed of small cells, showed the opposite pattern of immunostaining for CBD and SP. Many Leu-ENK-immunoreactive perikarya were observed in the dorsal NAC at its middle and caudal levels. There were moderate densities of Leu-ENK-positive fibers throughout the medial part of the NAC. At the dorsolateral margin of the NAC, Leu-ENK-positive fibers formed patches. Most NT-positive perikarya were found in the dorsolateral subdivision. SP-positive perikarya were scarce in the NAC. Dense distribution of NT-and SP-containing fibers or puncta were observed in the mediodorsal part (medial subdivision), where a dense field of DA-immunoreactive fibers was observed. The ventral part (ventral subdivision) contained moderate numbers of NT- and SP-immunoreactive fibers. Haloperidol-induced c-fos expression was very extensive in the medial half of NAC, particularly in the mediodorsal region, which overlapped with the DA- and peptide-rich region. The present study indicates that the NAC of the primate can be subdivided into at least three subterritories, the dorsolateral, medial and ventral subdivision, by neuropeptide histochemistry as well as by the response of its constituent neurons to haloperidol.

Distribution of nitric oxide synthase in the central nervous system of Macaca fuscata : subcortical regions

The distribution of nitric oxide synthase-immunoreactive neurons was studied in the Macaca fuscata by immunohistochemistry using antiserum against nitric oxide synthase. In the macaque lower brainstem, many nitric oxide synthase-containing cell bodies were found in the gigantocellular and parvocellular reticular nuclei, the nucleus of the spinal tract of trigeminal nerve, the cochlear nucleus, the prepositus hypoglossi and the nucleus of the solitary tract. Many nitric oxide synthase-immunoreactive perikarya were observed in the laterodorsal-pedunculopontine tegmental nucleus complex of the macaque pontine and midbrain tegmentum. In addition, there were many highly immunoreactive cell bodies in the superficial layers of the inferior and superior colliculi. In the forebrain, numerous cell bodies were observed in the caudate nucleus, putamen, nucleus accumbens, nucleus of the diagonal band, anterior perforated substance and amygdaloid complex. Whereas most of these neurons were labeled highly intense for nitric oxide synthase, there were also many lightly labeled nitric oxide synthase-immunoreactive neurons in the substantia innominata, globus pallidus, ansa peduncularis and lateral hypothalamic nucleus. The present observation indicated some species difference in the distribution of central nitric oxide synthase-containing neurons. Furthermore, the present neuroanatomical evidence that nitric oxide synthase is distributed in a variety of specific neuronal systems, with some differences in the patterns of cytoplasmic localization, further indicates the neural messenger role of nitric oxide in the central nervous system.

Regional cerebral blood flow in catatonic schizophrenia

Single photon emission computed tomography (SPECT) with 123I-iodoamphetamine (IMP) as tracer was used to study regional cerebral blood flow (rCBF) distribution in six patients with the catatonic subtype of schizophrenia (DSM-III-R). IMP-SPECT imaging revealed a significant reduction of rCBF in the parietal lobes of both hemispheres. Three-dimensional reconstruction of the SPECT images identified the superior region of the frontoparietal lobe as the most severely affected region. The pattern of rCBF deficits observed in catatonic schizophrenia differs markedly from that seen in 13 patients with other subtypes of schizophrenia and 7 normal control subjects. These observations indicate that parietal lobe dysfunction may be an important component in the pathology of the catatonic subtype of schizophrenia.

Electron-microscopic study of dopaminergic structures in the medial subdivision of the monkey nucleus accumbens

The medial subdivision of the monkey nucleus accumbens (NAC) is rich in dopamine (DA) and peptides. In the present investigation the mode of DA transmission in the medial subdivision was studied morphologically by light- and electron-microscopic immunocytochemistry using a monoclonal antibody raised against dopamine. The medial subdivision showed extremely dense accumulation of thick DA-immunoreactive varicose fibers. Electron-microscopic observation of single sections revealed that DA afferents had a relatively high incidence (33.2%) of asymmetric junctions in this area. Approximately 50% of the targets were dendritic shafts, 44.2% dendritic spines, and 5.1% somata. Some DA axons showed terminal profiles en passant within the synaptic complex, some of which showed synaptic triads. The unique ultrastructural features of DA terminals in the medial NAC indicate the existence of specific styles of DA transmission in the limbic structure.

The carbohydrate deposits detected by histochemical methods in the molecular layer of the dentate gyrus in the hippocampal formation of patients with schizophrenia, Down's syndrome and dementia, and aged person.

Post-mortem brain tissue was obtained from 28 patients with brain disorders, of which 15 had clinically diagnosed schizophrenia, 6 Alzheimer type dementia, 5 dementia with tangles and 2 cases of Downs syndrome. The controls were 22 cases from autopsies without brain disorders or with no known episodes of brain disorder. The tissues were stained for the detection of carbohydrate deposits in the hippocampal formation, using lectin, immunohistochemical and conventional staining methods. The staining revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate. The number of the deposits was higher in patients with brain disorder such as schizophrenia, Alzheimer type dementia, dementia with tangles or Downs syndrome, and in some aged individuals, in comparison to those in younger individuals. No deposits were detected in a few younger or aged individuals. Spherical deposits 3–10[emsp4 ]μm in diameter may be an immature form of the corpora amylacea, since they were similar in the histochemical characteristics with lectin, immunohistochemical and conventional staining methods. However, differing staining ability by hematoxylin, periodic acid Schiffs reagent and antibodies against the intracellular degraded proteins such as ubiquitin and tau-protein was observed. The antibodies against ubiquitin and tau-protein showed clear reactivity with the corpora amylacea and no reactivity with spherical deposits, indicating that the corpora amylacea has an intracellular origin and spherical deposits an extracellular matrix origin. The results obtained in this study indicate that not only neuronal degeneration but also unusual glycometabolism in neurons may disturb the neuronal function and cause brain disorders, and that spherical deposits may cause dysfunction of the neuronal network in the dentate gyrus of the hippocampus which is closely linked with recognition and memory functions.

Demonstration of a new dopamine-containing cell group in the primate rostral telencephalon.

The presence of dopaminergic neurons in the rostral forebrain has long been uncertain though the existence of tyrosine-hydroxylase (TH)-containing cells has been known in the region. Using an antibody to dopamine (DA), we demonstrated neurons immunoreactive (ir) to DA in the rostroventral striatum of the Japanese monkey (Macaca fuscata). The DA-ir cells were found at the ventral margin of the rostral part of the caudate nucleus, at the ventral margin of the rostral part of the nucleus accumbens, in the olfactory tubercle, and along the lateral margin of the putamen. These cells were intensely stained, small in size, and fusiform or ovoid in shape, and had one or two short processes. DA-ir cells were far smaller in number than TH-ir ones. The primates may possess a unique dopaminergic system in the rostral telencephalon.

The distribution of noradrenaline, serotonin and gamma-aminobutyric acid in the monkey nucleus accumbens.

1. The recent histochemical studies have shown that the primate nucleus accumbens (NAC) can be subdivided into at least three subdivisions, the medial, ventral and dorsolateral subdivisions. 2. The medical subdivision possesses dense peptide- and dopamine-immunoreactive (IR) fibers. 3. In order to further investigate the neurochemical characteristics of the primate NAC, the distribution of structures that contain noradrenaline (NA), serotonin (5-HT) and gamma-aminobutyric acid (GABA) were examined in the macaque monkey by using transmitter-immunohistochemical methods. 4. Many NA-IR fibers were observed in the dorsal part of the NAC, corresponding to the medial subdivision. Fine varicose 5-HT-IR fibers were evenly distributed in the NAC. GABA-IR cell bodies and puncta were observed throughout the NAC as well as in the caudate nucleus and putamen. 5. The monkey rostral NAC displays a highly homogeneous distribution of all neuropeptides and neurotransmitters studied so far and we propose that this region be termed the rostral subdivision of the NAC.

Transmitter biochemistry and histochemistry of the hypoplastic cerebellum in mice after neonatal administration of cytosine arabinoside

Administration of cytosine arabinoside, a DNA polymerase inhibitor, to mice (50 mg/kg body weight) on postnatal days 2, 3 and 4 resulted in severe hypoplasia of the cerebellar cortex accompanied by a large decrease in the cerebellar DNA and RNA contents. On postnatal days 10, 20, 30 and 70, concentrations of the putative neurotransmitters, noradrenaline and serotonin, were significantly increased in the affected cerebellum. In contrast, gamma-aminobutyric acid concentration was little changed, although a decrease in the content of gamma-aminobutyric acid per cerebellum was observed from postnatal day 20. No changes were found in the concentrations of these transmitter candidates nor in dopamine in the cerebral cortex or the brain stem. Histofluorescence observations revealed abnormally dense noradrenergic fibers in a poorly organized cerebellar cortex. The distribution of these fibers was characterized by a honeycomb pattern in the Purkinje cell and granular layers, and a dense plexus in the lower part of the thin molecular layer. However, the significance of neither the density of the noradrenergic fibers nor their abnormal distribution was apparent from the results of this study.

Computer-Aided Quantitative Analysis of the Distribution of Catecholamine-Containing Fibers in the Primate Prefrontal Cortex

The primate prefrontal cortex is densely innervated by midbrain dopamine (DA) neurons. Although the function of this mesocortical DA system is not known, it is believed that this catecholamine (CA) fiber system might be involved in certain mental disorders. In the present study, we investigated the CA innervation of the monkey prefrontal cortex by tyrosine hydroxylase (TH) immunohistochemistry, which is thought to be a reliable method to study cortical DA fibers.1 The density of TH-containing fibers was measured by a computer-aided image analysis technique.