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delta-Opioid receptor immunoreactivity: distribution in brainstem and spinal cord, and relationship to biogenic amines and enkephalin.

We have recently developed antisera which recognize epitopes of the cloned delta-opioid receptor (DOR; Dado et al., 1993). In the present report we have further characterized these antisera, and raised additional antisera in rats. We used these antisera to determine the distribution of DOR-like immunoreactivity (-Ll) in rat spinal cord and brainstem in relation to serotoninergic, noradrenergic, and enkephalinergic neurons. We found DOR-Ll in fibers and varicosities distributed throughout the spinal cord gray matter, with highest densities in the superficial dorsal horn, in autonomic regions, around the central canal as well as in the ventral horn motor nuclei. In the brainstem a dense innervation of DOR-immunoreactive (-IR) fibers was found in several nuclei such as spinal trigeminal nuclei, midline raphe nuclei, parabrachial nuclei, periaqueductal gray matter (PAG), interpeduncular nucleus, ans substantia nigra. A group of DOR-positive cells was seen in the laterodorsal tegmental nucleus. In addition, a few DOR-IR cell bodies were demonstrated in the parabrachial nuclei, interpeduncular nucleus, PAG, and superior and inferior colliculi as well as around the central canal in the spinal cord. All DOR-positive cells showed a punctuate staining pattern within the cytoplasm of the cell body and in primary dendrites. No plasma membrane staining of cells or dendrites could be demonstrated using the DOR antisera. Double-labeling experiments for DOR and 5-hydroxytryptamine (5HT, serotonin) revealed that some 5HT-IR neurons in the raphe complex were surrounded by DOR-IR fibers. In the spinal cord a high degree of coexistence was found between DOR and 5HT in nerve fibers and varicosities in the neuropil around the motoneurons and in lamina V of the dorsal horn. In autonomic regions of the spinal cord, a low degree of colocalization was seen between DOR and 5HT; in the superficial dorsal horn no coexistence was found. Tyrosine hydroxylase (TH)-positive neurons in the brainstem (in the A5 area, locus coeruleus, and A7 area) were apposed by DOR-positive fibers. However, no coexistence could be seen between DOR and TH in any part of the spinal cord. A close relation, but no coexistence, was observed between DOR- and enkephalin (ENK)-IR fibers in the spinal cord ventral horn; in the intermediolateral nucleus a low degree of colocalization was observed. Thus, a delta-opioid receptor may affect the activity of descending serotoninergic and noradrenergic neurons by means of modulating the release of neurotransmitters from afferents to these neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

[Changes of auditory brainstem response and auditory cortex response after exposure to intensive noise].

Auditory brainstem response and auditory cortex response were recorded repeatedly in 35 guinea pigs after exposure to intensive white noise (125 dB, 150 min.) for 62 d. the amplitude of evoked potential of acoustic nerve was decreased by 29% (P < 0.05), of the cochlear nuclei by 28% (P < 0.05). However, the amplitude of response of superior olives nuclei was increased by 21% (P < 0.05), of the inferior colliculi by 37% (P < 0.05), of the cortical evoked response by 131% (P < 0.001). The results indicate that the amplitudes of auditory evoked potential showed a centripital augmentation after exposure to intensive noise. The centripital augmentation was observed not only during the period of the temporary threshold shift (TTS) but also during that of the permanent threshold shift (PTS).

Animals↗

Regeneration of serotonergic immunoreactive fibers in the brain of 5,6-dihydroxytryptamine treated rat.

After the intraventricular injection of 5,6-dihydroxytryptamine (5,6-DHT), the course of degeneration and regeneration of the serotonergic fibers in the rat brain was studied immunohistochemically by using serotonin antiserum. Three days after 5,6-DHT treatment, an extensive disappearance of serotonin immunoreactive fibers was observed throughout the brain. Degenerative serotonergic fibers characterized by droplet-like swelling and intense staining by serotonin antiserum were detected in the following discrete areas, e.g., medial forebrain bundle (MFB), cingulate cortex, septal nucleus, diagonal band of Broca (DBB), lateral preoptic area, bed nucleus of stria terminalis, perifornical area, stria-terminals, raphe nuclei, ventral tegmental area, periaqueductal gray lateral reticular nucleus and nucleus of the solitary tract. The swelling were regarded as the proximal stumps of the chemically injured serotonin fibers. Sprouting serotonin fibers emanating from these swellings were observed 5 days after injection. The swollen thick fibers were seen up to 3 months thereafter throughout the brain, although they gradually decreased in number until 1 month after injection. On the contrary, the sprouting fibers extended their terminal fields throughout the brain. Three types of reorganization pattern of regenerating serotonergic fibers were distinguished: hyperinnervation, normoinnervation (similar to the normal innervation) and hypoinnervation patterns. In the areas with hyperinnervation, the density of the serotonergic fibers gradually increased for 3 months. These hyperinnervation patterns of regenerative serotonergic fibers were observed in the MFB, cingulate cortex, diagonal band of Broca, perifornical area, raphe nuclei, ventral tegmental area, motor trigeminal nucleus, facial nucleus, lateral reticular nucleus, inferior olivary complex and hypoglossal nucleus. On the other hand, the hypoinnervation displayed by a few regenerating serotonergic fibers was observed in the periventricular part of the prosencephalon, the ventromedial part of the hypothalamus, the dorsal hippocampus, the neocortex, the superior and inferior colliculi, the cerebellum, the dorsal tegmental nucleus of Gudden, the vestibular nuclei, the gracile nucleus and the cuneate nucleus. These reorganization patterns were formed 3 months after injection, and continued for a long time (2 years). The mechanisms of serotonergic fiber reorganization are discussed.

5,6-Dihydroxytryptamine↗

Sensorineural hearing loss: more than meets the eye?

PURPOSE: To assess the value of MR in patients with sensorineural hearing loss (SNHL) caused by lesions other than acoustic neuromas. METHODS: MR studies of 51 patients with SNHL were retrospectively reviewed; patients with acoustic neuroma were excluded to focus on the more uncommon causes. RESULTS: Twenty patients had labyrinthine lesions. Six patients had viral labyrinthitis, one patient had bacterial labyrinthitis, and one patient had luetic labyrinthitis. Three patients had hemorrhage in the labyrinth, two posttraumatic and one spontaneous from an adjacent temporal bone tumor. Only one of the two patients with traumatic labyrinthine hemorrhage had evidence of a fracture on high-resolution CT. In one patient with CT-proved cochlear otosclerosis, peri-cochlear foci of enhancement were seen on contrast-enhanced MR. Four patients had presumed labyrinthine schwannomas. A middle ear cholesteatoma in one patient invaded the cochlea and resulted in marked cochlear enhancement due to granulation tissue. Thirteen patients had intracanalicular and cerebellopontine angle lesions. The lesions included arteriovenous malformations (three patients), sarcoidosis (three patients), metastasis (two patients), lymphoma (two patients), lipomas (two patients), and postshunt meningeal fibrosis (one patient). Eighteen patients had intra-axial lesions responsible for SNHL. The most common intra-axial lesions were brain stem infarcts and multiple sclerosis. Traumatic lesions in the inferior colliculi, sarcoidosis, lymphoma, and extrinsic compression of the colliculi from a pineal tumor were also noted. CONCLUSION: MR can demonstrate numerous lesions responsible for SNHL other than acoustic neuromas. The entire acoustic pathways, including the labyrinth, internal auditory canal, cerebellopontine angle, and brain stem should be carefully scrutinized for lesions in patients with SNHL. The use of contrast media markedly increases the yield of MR in this clinical situation by demonstrating inflammatory and neoplastic labyrinthine lesions and meningeal pathology (both neoplastic and inflammatory) in the internal auditory canal and cerebellopontine angle cistern.

Adolescent↗

Context-dependent synaptic action of glycinergic and GABAergic inputs in the dorsal cochlear nucleus.

Cartwheel cells are prominent interneurons in the dorsal cochlear nucleus (DCN) that bear considerable homology to cerebellar Purkinje cells. They contact other cartwheel cells as well as fusiform cells, the principal cells of the DCN. In fusiform cells, the inhibition from cartwheel cells interacts with excitation mediated by granule cells and auditory nerve fibers, and shapes the output of the DCN in its ascent to the inferior colliculi. With intracellular recordings from anatomically identified cells in slices, synaptic inputs to fusiform and cartwheel cells were analyzed pharmacologically. Shocks to the auditory nerve and granule cell domains evoked glutamatergic, glycinergic, and GABA(A)ergic postsynaptic potentials (PSPs) in both cartwheel and fusiform cells. The temporal patterns of spontaneous and evoked glycinergic PSPs in fusiform and cartwheel cells were similar and mirrored the pattern of firing of cartwheel cells, probably reflecting the anatomical connections between these cell types and supporting the conclusion that cartwheel cells are glycinergic. In fusiform cells, glycinergic and GABA(A)ergic IPSPs evoked with shocks reversed at -68 mV on average. In marked contrast, glycinergic and GABA(A)ergic PSPs in cartwheel cells, as well as responses to exogenous application of 50-100 mM glycine or 100 microns muscimol, were depolarizing. Reversal potentials of PSPs and responses to glycine and muscimol were similar and averaged -52 mV. Glycinergic and GABA(A)ergic PSPs could elicit firing from cartwheel cells at their resting potentials, but could also reduce rapid firing during strong depolarizations. Thus, the action of glycinergic and GABA(A)ergic inputs on cartwheel cells depends on the electrophysiological context in which they occur.

2-Amino-5-phosphonovalerate↗

Mitochondrial NADH-coenzyme Q reductase deficiency in Leigh's disease.

A 4 1/2-month-old girl suffered from psychomotor retardation, generalized hypotonia, poor feeding, hyperreflexia, nystagmus, optical atrophy and choreoathetosis from the age of 3 months. Her blood lactate level was elevated to 40 mg/dL. Magnetic resonance imaging of her brain showed low T1 and high T2 signal intensities in the bilateral putamen, thalamus, red nuclei, substantia nigra, superior and inferior colliculi, cerebral peduncles and periaqueductal lesions. Muscle histochemistry and electron microscopic examinations were all normal except for variation in fiber size showing a myopathic change. An assay of muscle mitochondrial respiratory enzyme activities revealed a deficiency of NADH-coenzyme Q reductase. Molecular analysis did not reveal the putative T to G transversion at the nucleotide 8,993 of mitochondrial DNA in muscle biopsies. Leigh's disease was indicated by the clinical and radiologic manifestations. The patient died at 10 months of age from pneumonia and respiratory failure. There have been only sporadic reports of patients with Leigh's disease in Taiwan, and, to our knowledge, this is the first documented case of a Taiwanese patient with mitochondrial NADH-coenzyme Q reductase deficiency.

Base Sequence↗

Connections among functional areas in the mustached bat auditory cortex.

Connections among functional areas in the mustached bat's auditory cortex were examined by placing anatomical tracers in physiologically defined locations. We identified at least two and probably three channels connecting the various areas. One channel is formed by interconnections among areas containing neurons sensitive to frequency-modulated components (FMs) of the pulse and echo. These neurons are tuned to echo delay, a cue for target range, and thus define a ranging channel. An additional one or two channels are formed by interconnections among areas that contain neurons sensitive to the constant frequency components (CFs) of echoes. These neurons are of two main types: either sensitive to CFs of both pulse and echo (CF/CF neurons) or sensitive to a pulse FM and echo CF (FM-CF neurons). There was only a weak connection between the largest area of each type, suggesting they lie in different channels. Connections among areas in the ranging channel and echo CF-sensitive channel(s) were weak. Thus, the interconnections among functional areas in the mustached bat's auditory cortex define parallel channels for processing different types of biosonar information. Most corticocortical connections were patchy, in a manner suggestive of a columnar organization. The average width of the patches was approximately 360 microm. Based on the sizes of the functional areas, we estimate the auditory cortex contains a total of approximately 150 columns. Individual areas contain from as many as approximately 20 to as few as 1-4 columns. Each area had abundant projections outside of the auditory cortex. Connections within the cortex included the frontal, anterior cingulate, retrosplenial and perirhinal cortices, and the claustrum. Subcortical targets included the amygdyla, auditory thalamus, pons, pretectum, superior and inferior colliculi, and central gray. Projections within the cortex were of modest strength compared with several of the subcortical projections. Thus, the auditory areas themselves are the primary source of cortically processed biosonar information to the rest of the brain.

Animals↗

Distribution of dynorphin A (1-17) in the cat brainstem: an immunocytochemical study.

We have studied the distribution of cell bodies and fibers containing dynorphin A (1-17) in the brainstem of the cat using an indirect immunoperoxidase technique. The highest density of cell bodies was observed in the nucleus of the trapezoid body, whereas a low density of perikarya was found in the inferior and superior colliculi, nucleus of the brachium of the inferior colliculus and in the alaminar and laminar spinal trigeminal nuclei. A moderate density of immunoreactive fibers was found in the nucleus of the solitary tract, dorsal nucleus of the raphe, area postrema, dorsal motor nucleus of the vagus and in the marginal nucleus of the brachium conjunctivum, whereas a low density of fibers was observed in the lateral tegmental field, laminar and alaminar spinal trigeminal nuclei, nucleus of the trapezoid body, nucleus coeruleus, brachium conjunctivum, Kölliker-Fuse nucleus, periaqueductal gray and in the inferior and superior colliculi. The highest density of fibers containing dynorphin A was visualized in the substatia nigra. The widespread distribution of dynorphin A (1-17) immunoreactive structures suggests that the peptide could be involved in respiratory, cardiovascular, nociceptive and auditory mechanisms.

Animals↗

The amino acid sequence of bovine hypothalamic substance P. Identity to substance P from colliculi and small intestine.

Bovine substance P has been isolated in pure form from hypothalamic fragments and its complete amino acid sequence determined by studies performed on the intact peptide and on its isolated papain-generated fragments. Direct evidence for the positioning of each residue was obtained, amide assignments were unequivocally established, and the COOH-terminal residue was isolated and identified as Met-NH2. The results of total enzymic digestion performed on each of the peptides obtained argue against the presence of any non-amino acid constituents in the molecule. The amino acid sequence obtained is identical with that previously reported for material isolated form bovine colliculi and from equine small intestine.

Amino Acid Sequence↗

[Size of specific midbrain structures (external measurements)].

Measurements are given from the crus cerebri, brachia colliculorum, trigonum lemnisci (inferius), colliculi cranialis et caudalis, lamina tecti, tegmentum mesencephali, fossa interpeduncularis, frenulum veli medullaris cranialis and exitzone of trochlear nerve.

Anthropometry↗

Some neurochemical studies on auditory regions of mouse brain.

The mouse brain auditory pathway has been dissected into five regions: geniculate bodies, posterior colliculi, superior olives, cochlear nuclei, and cochleas. The following analyses were made in these regions and in the auditory cortex: protein, glutamate, gamma-aminobutyrate, taurine, choline acetyltransferase, and glutamate decarboxylase. Taurine levels (nmol . mg of protein-) were highest in cortex (93) and geniculate bodies (60) and lowest in the cochlear nuclei (27) and cochleas (29). Concentrations of gamma-aminobutyrate (same units) were highest in the geniculate bodies (28), low in the superior olives and cochlear nuclei (9 to 10), and undetectable in the cochleas. The distribution of glutamate decarboxylase activity reflected that of gamma-aminobutyrate. The activities of choline acetyltransferase (nmol . of acetylcholine synthesized . h . -1 mg of protein-1) were highest in the superior olives (60) and low in the cochleas (3). These results are interpreted as biocyemical support for previous physiological and pharmacological identification of the olivo-cochlear bundle as cholinergic and the cochlear-nucleus neurones as non-cholinergic. The results also provide further evidence for a role of GABA in the posterior colliculi, but not in the cochleas.

Animals↗

MR vs CT in progressive supranuclear palsy.

Nine progressive supranuclear palsy (PSP) patients were studied with computerized tomography (CT) and magnetic resonance (MR) in order to determine the efficacy of each in detecting atrophy of the brainstem. Three additional PSP patients were evaluated with MRI for quantitative (electronic) measurements of the colliculi, pons and midbrain tegmentum. Both CT and MRI were equally effective in demonstrating midbrain atrophy. The MR was able to utilize the sagittal view to visualize thinning of the collicular (quadrigeminal) plate, a useful sign in PSP. Atrophy of the thinned collicular plate is more pronounced in the superior colliculus, one of the most common sites of pathology in PSP. The MR is able to make quantitative measurements of the degree of atrophy of the colliculi, pons and midbrain tegmentum.

Adolescent↗

Somatostatin in the auditory system of the rat.

The present study clearly disclosed that the auditory system of the neonatal rat contains a large number of somatostatin (SRIF)-positive structures. Among them, n. cochlearis dorsalis and ventralis, n. ventralis lemnisci lateralis and n. parabrachialis colliculi inferioris contain huge collections of SRIF-positive neurons. Furthermore, the rat auditory system in general contains a number of SRIF-positive fibers.

Animals↗

Cloning, expression and pharmacology of the mouse 5-HT(4L) receptor.

Since most of our knowledge on pharmacological properties of brain 5-HT4 receptors have been discussed for mouse colliculi neurons, we cloned the corresponding receptor using the RT-PCR approach. As expected, the homology with the already cloned rat 5-HT(4L) receptor was high, revealing only 16 differences at the amino-acid level. One of the differences, proline75 in mouse, alanine75 in the already published rat sequences was not confirmed. Therefore this proline is part of the consensus sequence present in all 5-HT receptor transmembrane domain II (LVMP). Comparing the affinities of 11 agonists and five antagonists for the cloned mouse receptor (5-HT(4L))expressed in LLCPK1 and the corresponding receptor in mouse colliculi shows an excellent correlation. The transfected mouse 5-HT(4L) receptor stimulated cAMP production. When expressed at high density, it exhibited intrinsic activity. In contrast to the previously described distribution, we found that mRNA encoding for both the short (5-HT(4S))and the long form (5-HT(4L)) of 5-HT4 receptors are expressed in all mouse and rat brain areas.

Age Factors↗

[Compensatory processes after unilateral cutting of the brachia of the posterior colliculi in cats].

The ability for spatial analysis of stimuli of various sensory modalities was studied in cats with a unilateral section of the brachia of the posterior colliculi. To study the possible mechanisms of compensation of localization function in different periods following the brachia section, cortical evoked potentials to sound and light were recorded, and various areas of the neocortex removed (the temporal, parietal or sensorimotor). It was suggested that after a unilateral section of the brachia, compensation of localization of non-acoustic stimuli is linked with the recovery of interhemispheric functional symmetry within the corresponding analyser systems; localization of sound stimuli is restored primarily due to activation of the temporal neocortex in the intact hemisphere, i.e. involvement of one-hemisphere binaural mechanism.

Acoustic Stimulation↗