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C Broberger

Publications and source records attributed to C Broberger.

29 records · Page 2Linked to original sources
PubMed1998

Regulation of expression of neuropeptide Y Y1 and Y2 receptors in the arcuate nucleus of fasted rats.

Neuropeptide Y is expressed in neurons of the hypothalamic arcuate nucleus and has been ascribed a role as a stimulant of food intake. Neuropeptide Y Y1 and Y2 receptors are also localised in the arcuate nucleus, and it has been suggested that the Y1 receptor mediates part of the effect of neuropeptide Y on feeding behaviour. In the present study, immunohistochemistry and in situ hybridization were used to investigate the effect of food deprivation on the expression of Y1 and Y2 receptors in the arcuate nucleus of the rat. Fasting for 48 h induced a decrease in the number and area of Y1 receptor immunoreactive neurons in the arcuate nucleus. Furthermore, arcuate Y1 receptor mRNA levels also decreased after food deprivation. The decrease in the number of the Y1 receptor immunoreactive neurons was partially attenuated by supplementing the drinking water with 10% glucose. In contrast, fasting did not significantly change Y2 receptor mRNA levels in the arcuate nucleus. These results support the view that Y1 receptors in the arcuate nucleus play a role in the feeding pattern induced by neuropeptide Y.

Animals↗
PubMed1998

Modulation of motor behaviour by NMDA- and cholecystokinin-antagonism.

Motor behaviour relies on complex neurochemical interactions in the basal ganglia, in particular the striatum. Antagonistic influences in this region are exerted by afferent projections from, on the one hand, the ventral mesencephalon, utilizing dopamine as a transmitter, and, on the other hand, from the cerebral cortex, signalling by the excitatory amino acid glutamate. The activity in both these neuronal populations appears to be regulated by the neuropeptide cholecystokinin. This article concentrates on interactions between cholecystokinin and glutamate, summarizing some recent morphological, biochemical and behavioural findings. It is suggested that cholecystokinin, acting via the cholecystokininB receptor, potentiates the glutamatergic excitatory input to the striatum.

Animals↗
PubMed1998

Release of endogenous excitatory amino acids in the neostriatum of the rat under physiological and pharmacologically-induced conditions.

There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtypes, as a major excitatory neurotransmitter in the cortico-striatal pathway of the rat. Aspartate (Asp) is also present in cortico-striatal neurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesicles. Glu and Asp can be found at submicroM concentrations in the extracellular compartment of most areas of the basal ganglia. Their concentrations are largely regulated by transport mechanisms, but also by a synaptotagmin-dependent exocytotic release, and are sufficiently high to occupy junctional and extrajunctional receptors. We have investigated whether Glu and Asp release in the neostriatum can be selectively modulated by different neuronal systems. Dopamine (DA) and cholecystokinin (CCK) selectively stimulate Asp release, via D1 and CCKB receptor subtypes, respectively. Also opioid kappa-agonists increase Asp release. We propose that the selective modulation of Asp release by D1-, CCKB- and kappa-agonists involves striatal neurons containing Asp, but not Glu. In contrast, local perfusion with the mu-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) increases both Glu and Asp release. This effect is probably exerted on cortico-striatal terminals, via presynaptic inhibitory mu-receptors. Thus, these results demonstrate that extracellular levels of Glu and Asp are modulated differentially by different neuronal systems, and suggest that in the neostriatum of the rat there are neuronal populations using Glu and/or Asp as messenger(s).

Animals↗
PubMed1998

Neuropeptide Y: some viewpoints on a multifaceted peptide in the normal and diseased nervous system.

Using immunohistochemical and in situ hybridization methodologies the localization of neuropeptide tyrosine (NPY) and two of its receptors, the Y1- and the Y2-receptor (R), has been analysed in various tissues in normal animals and animals subjected to different experimental procedures as well as animals with a genetic and an acquired disease. (1) Dorsal root ganglion (DRG) neurons are discussed with special focus on the effect of peripheral nerve injury. In normal DRG neurons NPY cannot be detected, whereas Y1-R mRNA and Y1-R-like immunoreactivity (LI) are strongly expressed. The Y1-Rs decorate the membrane of the cell soma and are not transported peripherally into the axonal branches. Y2-R mRNA levels are low. After axotomy there is a marked increase in NPY, a decrease in Y1-Rs and an increase in Y2-Rs. The Y2-R is transported centrifugally. These findings suggest that NPY-ergic mechanisms participate in the adaptive changes of sensory neurons in response to injury. (2) Using specific antibodies the cellular and subcellular localization of the Y1-R protein have been analysed in cerebral blood vessels. The results demonstrate high concentrations of receptors in smooth muscle cells around pial arterioles with lower numbers in large vessels on the basal surface of the brain. In many regions the receptors 'disappear' after the arterioles have entered the brain tissue. At the ultrastructural level the receptors are found both on the endothelial and peripheral side of the muscle cells as well as laterally, where muscle cells oppose each other. The receptor protein is often associated with small vesicles. No NPY-positive nerve fibers were found around the Y1-R-rich arterioles, but they were only seen around the arteries with low Y1-R levels. The Y1-R-rich arterioles were, however, seen close to numerous NPY-positive fibers originating from central interneurons. These findings raise the possibility that centrally originating NPY can influence cerebral blood flow, possibly by stimulating NPY-Rs on the peripheral side of the muscle cells. However, also blood borne NPY, released under special conditions, such as stress from sympathetic nerves and the adrenal medulla and transported with blood, may stimulate receptors on the endothelial side of the smooth muscle cells. (3) In the arcuate nucleus Y1- and Y2-Rs are found, whereby the Y1-Rs are located in its ventro-medial portion and co-localized with POMC peptides, and the Y2-R in its ventromedial part, partly co-localized with NPY. NPY nerve endings makes synaptic contact with the POMC/Y1-R-positive neurons. In a mouse model for genetic anorexia very high levels of NPY were observed in arcuate neurons as compared to control mice. However, NPY mRNA levels were not different between the two groups. Taken together these findings are in good agreement with the view that NPY in the arcuate nucleus plays an important role in regulating feeding behaviour. (4) After intracerebral prion inoculation in mice an upregulation of NPY mRNA levels was observed in CA3 pyramidal neurons, and this effect was seen at a time point just before the first behavioural symptoms were manifested. At approximately the same time there was a dramatic decrease in Y2-R binding in strata oriens and radiatum of the CA1 region of the hippocampus, whereas in other regions no changes or much smaller changes were observed. Also, there was only a very slight decrease in Y2-R mRNA levels in CA3 neurons. It thus appears as if the prion disease prevents ligand binding to the Y2-R, perhaps by influencing traffic of receptor proteins, possibly at the level of cell membrane-associated caveolae, which have been implicated in the conversion of normal protein to scrapie protein. It is possible that these changes in NPY-ergic mechanisms may underlie some of the central symptoms associated with the prion disease. (ABSTRACT TRUNCATED)

Animals↗
PubMed1997

Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: altered processing of neuropeptide Y in the arcuate nucleus.

Neuropeptide Y is one of the most powerful neurochemical stimulants of food intake known. The neuronal substrate for this action is believed to be the neuropeptide Y-expressing cell population in the hypothalamic arcuate nucleus. In this study, mice homozygous for the anorexia mutation (anx) were investigated histochemically; anx is a recessive mutation that causes decreased food intake and starvation, leading to death 22 days after birth. We were interested to see whether any hypothalamic neurochemical abnormalities could be detected in this genetic model of starvation. By using immunohistochemistry and in situ hybridization, the hypothalamic distributions of neuropeptide Y, cholecystokinin, galanin, and serotonin, all messenger molecules postulated to be involved in the regulation of food intake and energy metabolism, were investigated. Immunoreactivities for somatostatin, the excitatory amino acid aspartate, and acetylcholinesterase were also studied. Neuropeptide Y-like immunoreactivity was increased markedly in arcuate cell bodies and decreased in terminals in the arcuate nucleus and other hypothalamic regions of anx/anx mice compared with normal litter mates. In situ hybridization for neuropeptide Y mRNA, however, showed no significant difference in gene expression in the arcuate nucleus. In addition, immunoreactivities for aspartate, acetylcholinesterase, and somatostatin in the arcuate nucleus were decreased in anx/anx mice. For cholecystokinin, galanin, and serotonin, no certain differences in hypothalamic immunoreactivity could be seen. These data suggest that a defect in neuropeptide Y-ergic signalling in the arcuate neurons may contribute to the failure to thrive in anx/anx mice.

Animals↗
PubMed1997

Cholecystokinin B receptor antagonists enhance the locomotor response to the N-methyl-D-aspartate antagonists phencyclidine and dizocilpine maleate.

The cholecystokinin antagonists L-740,093, L-365,260, LY-288513 and CI988, which are all selective for the cholecystokininB receptor subtype, were examined for their ability to modulate locomotor activity induced by the non-competitive N-methyl-D-aspartate receptor antagonists phencyclidine and dizocilpine maleate (MK-801) in habituated rats. It was found that the locomotor effects (motility, locomotion) produced by subcutaneous administration of phencyclidine (2 mg/kg) were significantly potentiated by intraperitoneal (i.p.) administration of L-740,093 (1 mg/kg), L-365,260 (10 mg/kg), LY-288513 (10 mg/kg), but not CI-988 (10 mg/kg). Locomotor activity induced by subcutaneous administration of MK-801 (0.15 mg/kg) was potentiated by intraperitoneal L-740,093 (0.3, 1 and 3 mg/kg). L-740,093, L-365,260, LY-288513 and CI-988 administered alone did not alter spontaneous locomotor activity (motility) as compared to vehicle/saline controls. However, when these antagonists were administered to naive, unhabituated rats, L-365,260 and LY-288513 caused a significant reduction in motility compared to the vehicle control. These findings suggest that, although cholecystokinin may be involved in exploratory behaviour exhibited by rats in a novel environment (unhabituated rats), its role is negligible in rats subjected to a familiar environment (habituated rats). Furthermore, these results support the interpretation that cholecystokinin has a suppressant effect on locomotion elicited by phencyclidine and MK-801, and that this inhibitory action of cholecystokinin is mediated via the cholecystokininB receptor, since it can be eliminated by administration of cholecystokininB antagonists. It is suggested that the site of action of the cholecystokininB receptors involves mainly the cholecystokinin/glutamate projection from the cortex to the anterior nucleus accumbens and/or striatum. Finally, the present study provides two examples of endogenous release of a neuropeptide resulting in behavioural consequences.

Animals↗
PubMed1997

Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus.

The arcuate nucleus of the hypothalamus houses a number of neurochemically different cell populations. Among these, a dense cluster of small neuropeptide-Y (NPY)-expressing neurons is located in its ventromedial subdivision and a pro-opiomelanocortin (POMC)-expressing neuron population in its ventrolateral part. Furthermore, both neuropeptide Y Y1 and Y2 receptors (Y1-Rs and Y2-Rs) are expressed in the arcuate nucleus. Here we analyse the co-expression of NPY and POMC/adrenocorticotropic hormone with the Y1-R and Y2-R in arcuate neurons using immunohistochemistry and in situ hybridization. Many, but not all, POMC neurons expressed Y1-R mRNA and protein. Conversely, several Y1-R-positive, POMC-negative neurons were found. NPY-positive nerve terminals were found in close apposition to Y1-R-like immunoreactivity localized close to the dendritic and somatic cell membranes. Y2-R mRNA was found in almost all NPY mRNA-expressing neurons, but also in a group of NPY mRNA-negative cells. These results show that the POMC neurons are targets for NPY, which is presumably present in, and released from, fibres originating in the ventromedial arcuate nucleus and which may play a role in NPY-induced feeding. Release of NPY, and possible coexisting messengers, may be controlled by presynaptic Y2-R expressed in NPY neurons. Taken together, the findings support the division of Y1-Rs and Y2-Rs into post- and presynaptic receptors, respectively.

Adrenocorticotropic Hormone↗
PubMed1994

Cholecystokinin B receptor gene expression in hypothalamic neurosecretory neurons after experimental manipulations.

Magnocellular neurons of the supraoptic (SON) and paraventricular (PVN) nuclei projecting to the neurohypophysis produce, in addition to the classical hormones vasopressin and oxytocin, a large number of other peptides, one of which is cholecystokinin (CCK). Binding sites for CCK have been identified in the posterior pituitary. Recently the cDNAs for CCKA and CCKB receptors were isolated and characterized, and CCKA and CCKB receptor mRNAs were localized in the SON and PVN. We have used complementary oligonucleotides and in situ hybridization histochemistry to study CCKB receptor mRNA in hypothalamic neurons. Changes in the expression of CCKB receptor mRNA in the SON and PVN were analysed in salt-loaded as well as in hypophysectomized animals. Levels of CCKB receptor mRNA in the PVN and SON increased markedly in salt-loaded animals as compared to controls. An increase in CCKB receptor mRNA levels was seen in the SON and PVN after 3 days of salt loading, with high levels continuing through 5 and 7 days. At 14 days, the levels of CCKB receptor mRNA in the PVN were significantly lower as compared to 7 days. Hypophysectomy 5 days prior to sacrifice, resulting in a nerve lesion in the neurohypophysial pathway and removal of the anterior pituitary hormones, induced a significant increase in CCKB receptor mRNA levels in neurons of the PVN. The increase in CCKB receptor mRNA labelling after salt loading was mainly observed in the ventrolateral part of the PVN and in the dorsolateral part of the SON, corresponding to oxytocin-containing neurons, whereas the increase after hypophysectomy was mainly seen in the central part of the PVN and in the ventral part of the SON, corresponding to vasopressin-containing neurons. The results suggest that the synthesis of CCKB receptors in magnocellular neurons is increased upon osmotic challenge and hypophysectomy.

Animals↗
PubMed1993

Marked increase in cholecystokinin B receptor messenger RNA levels in rat dorsal root ganglia after peripheral axotomy.

It is now well established that the expression of peptides in rat primary sensory neurons is dramatically changed in response to peripheral nerve injury. Thus, as first shown by Jessell et al. peripheral axotomy causes a decrease in substance P levels in the dorsal horn of the corresponding spinal cord segments, and this is due to down-regulation of peptide synthesis in dorsal root ganglion neurons. In contrast, other peptides such as vasoactive intestinal polypeptide and peptide histidine isoleucine, galanin and neuropeptide Y are all markedly upregulated in the rat L4 and L5 dorsal root ganglia after sciatic nerve sectioning. The levels of another peptide, cholecystokinin and its messenger RNA are normally very low or undectable in rat primary sensory neurons, but after peripheral axotomy approximately 30% of the ganglion neurons express cholecystokinin messenger RNA. During the last few years a number of peptide receptors have been cloned, and they all belong to the family of G-protein coupled receptors with seven membrane spanning segments, among them the two cholecystokinin receptors cholecystokininA and cholecystokininB. Ghilardi et al. have recently described presence of cholecystokininB binding sites in rat dorsal root ganglia neurons. In the present study we report that the messenger RNA for the cholecystokininB receptor is present at very low levels in normal dorsal root ganglia of the rat, but axotomy causes a very marked increase in the number of sensory neurons of all sizes expressing cholecystokininB receptor messenger RNA, suggesting an increased sensitivity to cholecystokinin for many primary sensory neurons of different modalities after lesion.

Animals↗
PubMedDate not supplied

Hypothalamic and vagal neuropeptide circuitries regulating food intake.

It has been recognized for some time that a number of different neuropeptides exert powerful effects on food intake. During the last few years, the neurocircuitry within which these peptides operate has also begun to be elucidated. Peptidergic feeding-regulatory neurones are found both in the hypothalamus and the brainstem, where they act as input stations for hormonal and gastrointestinal information, respectively. These cell populations both project to several other brain regions and interconnect extensively. The present review summarizes the neuroanatomy and connectivity of some prominent peptides involved in food intake control, including neuropeptide Y, melanocortin peptides, agouti gene-related protein, cocaine- and amphetamine-regulated transcript, orexin/hypocretin, melanin-concentrating hormone and cholecystokinin. Disturbances in the hypothalamic neuropeptide systems have been implicated in the phenotype of a genetic model of fatal hypophagia, the mouse anorexia (anx) mutation, which is also discussed.

Animals↗