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M Schultzberg

Publications and source records attributed to M Schultzberg.

At least 73 records · Page 4Linked to original sources
PubMed1989

Distribution of TRH-like immunoreactivity with special reference to coexistence with other neuroactive compounds.

During the last years, several important advancements have been made that are of importance for our understanding of the distribution and localization of neurons and cells producing TRH-LI. As detailed in other chapters in this volume, the precursor for TRH has been characterized that has allowed production of antibodies raised against specific sequences of this precursor. This, in turn, has provided new tools for the immunohistochemical elucidation of TRH systems in the CNS. The TRH precursor has also been cloned, leading to possibilities for studying the localization of TRH mRNA with in situ hybridization. Finally, as shown in this paper, improvement of the fixation technique has made it possible to visualize extensive TRH-immunoreactive cell body and fiber systems with antiserum raised against the TRH tripeptide. The results from the latter studies and those with antisera directed to the TRH precursor and in situ hybridization are in good agreement, with some minor exceptions. It should be pointed out that some of the systems described here, for example TRH positive-cell bodies in cortical areas and the hippocampal formation, contain only a very weak immunoreactivity. As always with immunohistochemical techniques, the possibility of crossreactivity with TRH-like peptides or TRH-like sequences within larger proteins must be considered. The present results confirm the presence of TRH-LI in the insulin-producing beta cells of the pancreas, which with the improved technique can be demonstrated also in early adulthood in rats and guinea pigs. Moreover, it could be established that TRH-LI is present in neurons in the gastrointestinal tract as well as in a population of endocrine cells in the antrum of the stomach of the guinea pig. These cells seem at least partly to be identical to the well-known gastrin-producing cells. TRH-LI has been observed to occur in neurons already containing a classical transmitter and/or other peptides. Of particular importance here seems to be a descending bulbospinal system that in addition to TRH co-contains 5-HT, substance P-LI, galanin-LI, human growth hormone immunoreactive material, and proctolin-like material. The significance of this coexistence is not well understood, but interesting interactions have been observed. Attempts to manipulate the TRH phenotype in these medullary neurons by transplantation to other sites in the brain has so far shown that the expression of this peptide seems fairly stable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Spread of Trypanosoma brucei to the nervous system: early attack on circumventricular organs and sensory ganglia.

The distribution of Trypanosoma brucei brucei in the nervous system of experimentally infected Sprague-Dawley rats and BALB/c and deer mice was examined with immunohistochemical techniques. The trypanosomes showed an early invasion in areas lacking a so-called blood-brain or blood-nerve barrier, i.e., in sensory ganglia and circumventricular organs including the area postrema, pineal gland, and median eminence. This distribution of trypanosomes may relate to the origin of cardinal symptoms of the disease, e.g., sensory disturbances, nausea, disturbed circadian rhythm, and neuroendocrinological dysfunctions. Trypanosome infections in rodents may provide a model for studies of how an infectious agent or factors released by the immune response may relatively selectively interfere with these functionally defined regions of the nervous system.

Animals↗
PubMed1988

DARPP-32 as a marker for D-1 dopaminoceptive cells in the rat brain: prenatal development and presence in glial elements (tanycytes) in the basal hypothalamus.

The present article reviews some aspects of the localization of a dopamine- and cyclic AMP-regulated phosphoprotein, DARPP-32, which is assumed to be present in D-1 dopaminoceptive neurons. Its prenatal development starts at day 14 of gestation, is to a large extent complete at birth and seems to be independent of ingrowing dopamine-containing afferents. Rearrangements occur in certain areas, and in some systems DARPP-32 appears to be only transiently expressed. The presence of DARPP-32 in glial structures, the tanycytes, in the arcuate nucleus-median eminence complex in the mediobasal hypothalamus, has given further support to the hypothesis that dopamine, by controlling the shape of the tanycytes and the extension of their processes, can regulate LHRH release by a 'mechanical mechanism'. This hypothesis is now being examined in some experimental paradigms.

Animals↗
PubMed1988

Transmitter expression and morphological development of embryonic medullary and mesencephalic raphé neurones after transplantation to the adult rat central nervous system. II. Grafts to the hippocampus.

Suspensions of cells taken from the mesencephalic or medullary raphé regions of the 13-14 day old embryonic rat brain were injected into the hippocampus of adult rats which had previously been denervated of its serotoninergic input by 5,7-dihydroxytryptamine. At periods of up to 14 months after implantation, the brains were taken for immunohistochemical analysis of 5-hydroxytryptamine (5HT)-, substance P (SP)- and thyrotropin releasing hormone (TRH)-like immunoreactivity. Surviving grafts were found in all animals. The implants derived from mesencephalic raphé contained neurones immunoreactive to 5HT, SP or both substances together. On average 19% of the potential number of mesencephalic 5HT neurones were found in the grafts. Outgrowth of 5HT-immunoreactive fibres was extensive, and displayed the typical pattern of 5HT innervation in the normal hippocampus-the densest plexuses were found in the dentate gyrus, with sparser networks in the CA1 and CA2 regions. SP-positive processes were principally found only in the graft itself. Transplants of medullary raphé cells contained 5HT-immunoreactive neurones, some of which also contained SP-and/or TRH-like immunoreactivity, thereby mirroring the situation found in the caudal raphé complex in situ. An average of 18% of the total available medullary serotoninergic neurones were found at each graft site. A rich outgrowth of 5HT-immunoreactive varicose processes was evident, with the same pattern as the 5HT innervation by the mesencephalic raphé grafts, and as in the normal hippocampus. SP- and TRH-positive fibres were essentially detectable only in the graft, but not in the host hippocampus. The present studies indicate that the milieu of the hippocampus does not preferentially attenuate the survival of the serotoninergic cells which do not normally project to it. Nor is the fibre outgrowth of these medullary raphé 5HT neurones significantly different from that of the mesencephalic raphé. However, the hippocampal environment may be responsible for the appearance of SP-LI in the otherwise apparently solely 5HT-containing mesencephalic raphé neurones, and for repressing the outgrowth of fibres containing TRH-, or SP-like immunoreactivity, regardless of their origin.

5,7-Dihydroxytryptamine↗
PubMed1988

Transmitter expression and morphological development of embryonic medullary and mesencephalic raphé neurones after transplantation to the adult rat central nervous system. III. Grafts to the striatum.

Implants have been made of dissociated embryonic mesencephalic or medullary raphé cells into the adult rat striatum, previously depleted of its 5HT innervation. The transmitter complement and fibre outgrowth of the grafted neurones were analysed immunocytochemically. Serotonin-containing cells were found in both types of transplant, and the proportionate survival of the potential number of implanted 5HT cells was similar for each type of graft. However, these proportions were both greater than that described previously in transplants of mesencephalic raphé cells to the spinal cord. In addition, the proportionate survival of medullary substance P neurones grafted to the striatum was greater than that of medullary 5HT cells implanted in the same region. The transmitter complement of the medullary neurones was largely unaltered after transplantation. However, the mesencephalic grafts contained neurones storing 5HT- and/or substance P-, or TRH-like immunoreactivity. The 5HT/substance P and TRH neurones have so far not been encountered in the mesencephalon in situ using the present immunohistochemical methodology. Invasion of the host striatum by 5HT processes from the transplanted mesencephalic cells was extensive. Fibres from medullary raphé neurones, however, were restricted principally to within the graft itself. It is concluded that there may exist in the adult rat striatum a set of trophic factors for 5HT and substance P neurones different from those found in other regions of the central nervous system, such as spinal cord. Moreover, trophic agents in the host striatum appear to operate differentially on mesencephalic and medullary raphé 5HT neurones to regulate their axonal outgrowth. Lastly, the neurotransmitter phenotypic expression of the embryonic mesencephalic raphé cells may be susceptible to influences from the host environment.

Animals↗
PubMed1988

Neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide-immunoreactive nerves in bone and surrounding tissues.

Nerve fibres immunoreactive to neuropeptide Y (NPY), tyrosine hydroxylase (TH) and vasoactive intestinal polypeptide (VIP) were demonstrated in rat bone and adjacent tissues. The distribution of NPY- and TH-positive fibres differed from that of VIP-positive fibres. NPY- and TH-immunoreactive fibres were almost exclusively found close to or within the blood vessel walls, mostly in the vicinity of the epiphyseal plate, but also in the Volkmann canals. VIP-positive fibres were predominantly present in the epiphysis and periosteum and only occasionally around blood vessels. This study demonstrates that bone and surrounding tissues have a supply of both noradrenergic and peptide-containing nerves. The differential distribution of these nerves may reflect specific roles in the local regulation of bone physiology, such as blood flow, bone formation or resorption.

Animals↗
PubMed1988

Distribution of DT diaphorase in the rat brain: biochemical and immunohistochemical studies.

DT diaphorase [NAD(P)H:quinone oxidoreductase] activity was measured in subcellular fractions from homogenates of striatum, frontal cortex, hippocampus, cerebellum, hypothalamus and substantia nigra. This flavoprotein, which by definition oxidizes dihydronicotinamide adenine dinucleotide and dihydronicotinamide adenine dinucleotide phosphate at equal rates and is completely inhibited by 10(-5) M dicoumarol, was found to constitute 80-90% of the total dihydronicotinamide adenine dinucleotide- and dihydronicotinamide adenine dinucleotide phosphate-reductase activities in all brain regions studied. Antibodies raised against purified cytosolic DT diaphorase from the rat liver cross-reacted with the brain enzyme and inhibited soluble DT diaphorase from striatum and cerebellum to 80-90%. Immunohistochemical studies with the same antibodies demonstrated the occurrence of DT diaphorase immunoreactivity in a population of neurons in the substantia nigra and ventral tegmental area. In some neurons there was a colocalization of DT diaphorase and tyrosine hydroxylase-like immunoreactivity. The dense network of DT diaphorase-immunoreactive fibres in the striatum disappeared along with the dopaminergic innervation after 6-hydroxydopamine lesion. DT diaphorase immunoreactivity was also found in Bergmann glia, astrocytes and tanycytes. No correlation appeared to exist between the localization of neuronal DT diaphorase immunoreactivity and the dihydronicotinamide adenine dinucleotide phosphate-diaphorase-like activity, as defined by tetrazolium salt staining, used as a marker for certain peptidergic and cholinergic neurons. However, in, for example, glial cells in the cerebellum, DT diaphorase might contribute or be responsible for the histochemical dihydronicotinamide adenine dinucleotide phosphate-diaphorase activity.

Animals↗
PubMed1988

Ontogeny of the dopamine and cyclic adenosine-3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the pre- and postnatal mouse central nervous system.

The ontogeny of a dopamine and cyclic adenosine-3':5'-monophosphate-regulated phosphoprotein with an apparent molecular weight of 32 kilodaltons (DARPP-32) has been studied in the central nervous system of the prenatal, newborn and adult mouse. DARPP-32-immunoreactive somata were first identified at day 12 of gestation, in the primary olfactory cortex and in the ventrolateral medulla oblongata. On day 14 of gestation, neurons containing DARPP-32-like immunoreactivity became apparent in the caudate nucleus, olfactory tubercle, nucleus accumbens, frontoparietal cortex and the ventral medulla oblongata. During the period up to and including birth, the number of cell bodies and fibres in all these areas increased markedly. In addition, DARPP-32-positive neurons became visible in the olfactory nucleus, the arcuate nucleus, and DARPP-32-positive cells appeared in the choroid plexus of the lateral, third and fourth ventricles. DARPP-32-containing fibres could be seen in the median eminence, the ventrolateral thalamus, and in the striatonigral projection, descending in the internal capsule to ramify extensively in the substantia nigra. Only in the cerebellum and suprachiasmatic nucleus did the development of DARPP-32-like immunoreactivity occur postnatally. The development of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis, was simultaneously examined. The arrival of the tyrosine hydroxylase-containing projection to the caudate nucleus, the olfactory tubercle and the nucleus accumbens apparently occurred 1-2 days after the appearance of DARPP-32-immunoreactive cells within these regions. In the ventral and ventrolateral medulla oblongata, and the primary olfactory cortex, no tyrosine hydroxylase innervation was seen near the DARPP-32-positive neurons at days 12-14. The organization of the DARPP-32-containing somata of the caudate nucleus into aggregates of 5-15 neurons was partly paralleled spatially by an increased density of tyrosine hydroxylase-positive fibres. Many DARPP-32-immunoreactive cells in the immature mouse brain are present by the day of birth, particularly in the areas known to receive a dopaminergic innervation. The development of these presumptive dopaminoceptive DARPP-32-containing neurons does not seem to be dependent on the presence, however, of a dopaminergic input, since in all regions examined DARPP-32-LI preceded the appearance of tyrosine hydroxylase-like immunoreactivity by at least 1-2 days. Indeed, the results suggest that the existence of DARPP-32-like immunoreactivity in cell bodies and dendrites may be a pre-requisite for the formation or subsequent stabilization of dopaminergic synapses.

Aging↗
PubMed1987

Distribution of neuropeptide Y receptors in the rat hippocampal region.

The distribution of binding sites for neuropeptide Y (NPY) was studied in the rat hippocampal region by using [3H]NPY together with quantitative in vitro receptor autoradiography. The highest density of specifically bound [3H]NPY was found in regio superior and regio inferior of Ammon's horn. Within these fields, stratum oriens, stratum pyramidale and stratum radiatum harboured the highest densities of [3H]NPY binding while stratum moleculare was relatively poor in [3H]NPY binding sites. In area dentata, the highest density of [3H]NPY binding was found in the inner one third of the molecular layer. In the presubiculum and in the entorhinal area, the outer two layers were slightly more enriched in [3H]NPY binding sites than were the deep layers. In all hippocampal subfields a clear gradient of increased [3H]NPY binding was found at successively more ventral levels.

Animals↗
PubMed1987

Interleukin-1-like immunoreactivity in peripheral tissues.

Rabbit antisera were raised against a synthetic peptide corresponding to the amino acid residues 169-194 in the murine interleukin-1 sequence. Immunoreactive varicose fibers were observed in the vas deferens, urinary bladder, gastrointestinal tract, and coeliac-superior mesenteric ganglion complex of the rat. Fibers were also encountered around blood vessels in several organs including the thymus, spleen, lymph nodes, liver, and kidney.

Amino Acid Sequence↗
PubMed1987

Development of a dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the prenatal rat central nervous system, and its relationship to the arrival of presumptive dopaminergic innervation.

The development of a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with an apparent Mr of 32,000 (DARPP-32) has been investigated in the central nervous system of the prenatal and newborn rat by immunocytochemical methods. DARPP-32 first appears in the rat brain at day 14 of gestation, in the anlage of the primary olfactory cortex and the caudate nucleus. Over the next few days, the number of immunoreactive cell bodies in these 2 areas, and in the olfactory tubercle and frontal cortex, increases rapidly. By the day of birth, most of the brain regions that will ultimately contain DARPP-32-positive somata already display a disposition toward DARPP-32-like immunoreactivity similar to that observed in the adult animal. In addition to the nuclei mentioned above, DARPP-32-containing cell bodies also appear over the intervening period in the olfactory nucleus, nucleus accumbens, central amygdaloid nucleus, lateral funiculus, and the choroid plexus and ependymal layers of the third, fourth, and lateral ventricles and the Sylvian aqueduct. Many of these immunoreactive cells disappear during subsequent postnatal maturation. DARPP-32-immunoreactive fibers were also observed in the prenatal and newborn rat CNS. As in the adult, the processes were observed in known target areas of the DARPP-32-containing neurons, namely, the globus pallidus, ventral pallidum, internal capsule, and substantia nigra. The ontogeny of tyrosine hydroxylase (TH)-like immunoreactivity was analyzed simultaneously. Of particular interest was the observation that the arrival within a given brain region of the presumed dopaminergic, TH-containing innervation, part of whose postsynaptic function is putatively mediated by DARPP-32, was preceded by at least 2 d by the appearance of the DARPP-32-containing cells. Moreover, the subsequent reorganization of the DARPP-32-positive somata within the caudate nucleus into distinct clumps also predated by 1 or 2 d the aggregation of the TH fibers into the same microzones. The development of DARPP-32-like immunoreactivity is mostly complete by the day of birth, and is consistent with its playing a role in mediating some of the postsynaptic actions of dopamine pathways. The appearance of this protein does not seem to be dependent on the presence of a dopaminergic innervation.

Animals↗
PubMed1985

Ontogeny of phenylethanolamine N-methyltransferase- and tyrosine hydroxylase-like immunoreactivity in presumptive adrenaline neurones of the foetal rat central nervous system.

The appearance of phenylethanolamine N-methyltransferase (PNMT)- and tyrosine hydroxylase (TH)-like immunoreactivity (LI) in the foetal rat central nervous system has been investigated. Antibodies raised against PNMT and TH were used in an indirect immunofluorescence method. Attention was focussed on areas containing putative adrenaline-containing nerve cell bodies or fibres and, using an elution-restaining technique, it was possible to analyze whether neurones contained PNMT-LI, TH-LI, or both. PNMT-immunoreactive neurones could first be visualized on day 13 of gestation, in the ventrolateral and dorsal medulla oblongata, and probably corresponding to those of the C1 and C2 groups. The number of positive cell bodies and the intensity of their fluorescent staining in these areas were not dissimilar at this stage to the number and intensity observed at 1 day postnatal, the final age studied. At day 16, PNMT-positive cells were observed for the first time in midline areas of the rostral dorsal medulla oblongata-caudal pons, associated with the medial longitudinal fasciculus. These cells probably composed the C3 cell group. Many PNMT-immunoreactive fibres could be seen at day 13 of gestation, in the medulla, and coursing both in an ascending bundle around the mesencephalic flexure and in a descending bundle toward the spinal cord. The extent of the bundles increased with gestational age, such that dense meshworks of PNMT-immunoreactive varicose fibres were visible ventral to the aqueductus Sylvii, and the periventricular and lateral regions of the hypothalamus by days 18 to 19, and in the paraventricular nucleus, the septum, and the thoracic spinal cord by day 1 after birth. A sparser fibre plexus was observed in the amygdala at day 1 postnatal. In contrast to the explosive appearance of PNMT-immunoreactive cells at day 13 of gestation, the development of TH-LI within these same neurones was much more protracted. Only rarely were TH-LI and PNMT-LI colocalized at day 13, and even at birth TH-LI could not be visualized in 5% of PNMT-immunoreactive cells in the ventrolateral medulla oblongata, and in 50% of those in the dorsal vagal complex. A similar tardy appearance of TH-LI in PNMT-immunoreactive fibres was observed also. It should be emphasized that strongly TH-immunoreactive neurones were found already at gestational day 10.5 in the medulla oblongata, caudal to the PNMT-immunoreactive cells. It is concluded that the expression of enzymes involved in the synthesis of adrenaline is not unitarily controlled, and may be partly dependent on other than epigenetic factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Transmitter expression and morphological development of embryonic medullary and mesencephalic raphé neurones after transplantation to the adult rat central nervous system. I. Grafts to the spinal cord.

Suspensions of cells derived from the mesencephalic raphé or medullary raphé regions of the 13-14 day old embryonic rat brain were injected into the spinal cord of adult rats which had been previously denervated with 5,7-dihydroxytryptamine. At periods of up to 12 months after grafting, the spinal cords were taken for immunohistochemical analysis of 5-hydroxytryptamine (5HT), substance P (SP) and thyrotropin releasing hormone (TRH). In nearly all cases, surviving transplants were found. The grafts derived from mesencephalic raphé cells contained neurones which were immunoreactive to 5HT, or SP, but not both together. On average 4% of the total possible number of the available embryonic mesencephalic serotoninergic cells were found. A very dense outgrowth of 5HT positive fibres from the transplant was observed, extending up to 1.5 cm in both the caudal and rostral directions from the graft locus. Some SP immunoreactive fibres were also apparent near the implant. The grafts derived from the medullary transplant also contained 5HT-immunoreactive cells, comprising on average 25% of the total 5HT neurones available from the embryonic medullary primordium. In addition, neurones co-localizing 5HT together with SP and TRH were visible, closely reflecting the situation found in the medullary raphé in situ. Dense plexi of fibres containing 5HT-LI extended both caudally and rostrally up to 12-15 mm from the transplant. Outgrowth of SP and TRH varicose fibres was also demonstrable, although to a lesser degree than for 5HT. It was also possible to find many motoneurones surrounded by varicose fibres containing both 5HT and SP, in contrast to the situation with the mesencephalic grafts, where no such patterns of innervation were seen. The experiments indicate that the milieu of the spinal cord may compromise the survival of mesencephalic raphé 5HT neurones far more than of medullary serotonin cells. However, despite this effect on cell survival, the outgrowth of fibres from the remaining mesencephalic 5HT neurones was apparently unaffected by their ectopic position. Similarly, the transmitter content of both classes of raphé cells was largely unaltered, either by the transplantation process or by the environment into which they were placed. It is concluded that although the adult denervated spinal cord can selectively affect neuronal survival, it is incapable either of inducing in other serotoninergic cells placed within it the transmitter phenotype typical of medullary raphé neurones, or of causing those ectopically located 5HT cells to form connections appropriate to the descending serotonin fibres.

Animals↗
PubMed1985

Differential ontogeny of three putative catecholamine cell types in the postnatal rat retina.

The development of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) in the rat retina was investigated using the indirect immunofluorescence technique. Two types of TH-positive cells were found. The first appeared at postnatal day 2, in the vitreal half of the inner nuclear layer (INL). Single fibres from these neurones, bifurcating in and innervating layer 3 of the inner plexiform layer (IPL) were seen at day 4. This first type of TH-positive cell was most numerous at day 15, but thereafter disappeared before adulthood. At day 5, a more intensely staining TH-immunoreactive neurone became visible, occupying a more proximal part of the INL, and projecting multiple fibres to layer 1 of the IPL. In contrast, PNMT-positive cells, in the vitreal half of the INL and in the ganglion cell layer (GCL), sending single varicose axons to layer 3 of the IPL, were first apparent only at day 10, achieving a disposition similar to that of the adult by days 15-16 postnatal. Analysis of adjacent sections stained with antibodies to TH and PNMT revealed that neither type of TH-positive neurone also contained PNMT-like immunoreactivity. It is concluded that although both of the rate-limiting enzymes of the catecholamine synthetic pathway are present in the developing rat retina, they occur in 3 mutually exclusive populations of neurones.

Animals↗
PubMed1985

Cholecystokinin in intracerebral transplants.

Fetal mesencephalic tissue containing dopamine and cholecystokinin-immunoreactive neurons was grafted to the striatum of adult host rats, either as solid pieces of tissue or as cell suspensions. The dopaminergic innervation of the striatum was previously ablated unilaterally by neurotoxin. Immunohistochemical analysis using antibodies to cholecystokinin and tyrosine hydroxylase was performed at least 8 weeks after grafting. Neurons immunoreactive to tyrosine hydroxylase or cholecystokinin, as well as neurons immunoreactive to both compounds were found in the transplants. In the solid tissue grafts the proportions of neurons exhibiting either CCK- or tyrosine hydroxylase-like immunoreactivity to neurons exhibiting both immunoreactivities were similar to those seen in intact ventral mesencephalon. This suggests that these neurons are able to maintain and express their transmitter phenotypy when transplanted to an ectopic location. An extensive outgrowth of fibers containing tyrosine hydroxylase-like immunoreactivity, but apparently lacking cholecystokinin-like immunoreactivity, was observed in the host striatum. Cholecystokinin-immunoreactive fibers were found in a narrow zone immediately adjoining the graft. The results suggest the possibility that growth-regulating mechanisms in the denervated host striatum selectively favor the ingrowth of fibers from the appropriate dopaminergic neuronal subset.

Animals↗