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B J Oldfield

Publications and source records attributed to B J Oldfield.

At least 19 recordsLinked to original sources
PubMed2006

Effect of central administration of QRFP(26) peptide on energy balance and characterization of a second QRFP receptor in rat.

The recently identified neuropeptide QRFP(26) is predominantly expressed in the hypothalamus and was suggested to play a role in the regulation of food intake following the observation of an acute orexigenic effect after central administration in mice. QRFP(26) exerts its effect via GPR103 and a newly identified receptor in mouse. The aim of our study was (a) to investigate the distribution of QRFP(26) and a newly discovered QRFP receptor mRNA in rat and (b) to further characterize the effects of central administration of QRFP(26) on energy balance in rats. QRFP(26) mRNA was detected in the retrochiasmatic nucleus, periventricular nucleus, arcuate nucleus and restricted areas of the lateral nucleus of the hypothalamus. We found an additional receptor with high homology for GPR103 in rat. This receptor increases inositol triphosphate production in transfected cells in presence of QRFP(26) and its mRNA was particularly enriched in ventral and posterior thalamic groups, anterior hypothalamus and medulla. When QRFP(26) (10 microg and 50 microg) was administered centrally before the start of the light phase both doses increased food intake for 2 h after injection without reaching statistical significance. QRFP(26) caused no changes in locomotor activity or energy expenditure. In summary, central QRFP(26) injection causes slight and transient hyperphagia in rats without changing any other energy balance parameters after 24 h. We conclude that QRFP(26) has limited impact on the central regulation of energy balance in rats and that its essential function remains to be clarified.

Amino Acid Sequence↗
PubMed2004

Physiological and pathophysiological influences on thirst.

Thirst motivates animals to seek fluid and drink it. It is regulated by the central nervous system and arises from neural and chemical signals from the periphery interacting in the brain to stimulate a drive to drink. Our research has focussed on the lamina terminalis and the manner in which osmotic and hormonal stimuli from the circulation are detected by neurons in this region and how that information is integrated with other neural signals to generate thirst. Our studies of osmoregulatory drinking in the sheep and rat have produced evidence that osmoreceptors for thirst exist in the dorsal cap of the organum vasculosum of the lamina terminalis (OVLT) and in the periphery of the subfornical organ, and possibly also in the median preoptic nucleus. In the rat, the hormones angiotensin II and relaxin act on neurons in the periphery of the subfornical organ to stimulate drinking. Studies of human thirst using functional magnetic resonance imaging (fMRI) techniques show that systemic hypertonicity activates the lamina terminalis and the anterior cingulate cortex, but the neural circuitry that connects sensors in the lamina terminalis to cortical regions subserving thirst remains to be determined. Regarding pathophysiological influences on thirst mechanisms, both excessive (polydipsia) and inadequate (hypodisia) water intake may have dire consequences. One of the most common primary polydipsias is that observed in some cases of schizophrenia. The neural mechanisms causing the excessive water intake in this disorder are unknown, so too are the factors that result in impaired thirst and inadequate fluid intake in some elderly humans.

Animals↗
PubMed2004

Vasopressin secretion: osmotic and hormonal regulation by the lamina terminalis.

The lamina terminalis, located in the anterior wall of the third ventricle, is comprised of the subfornical organ, median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT). The subfornical organ and OVLT are two of the brain's circumventricular organs that lack the blood-brain barrier, and are therefore exposed to the ionic and hormonal environment of the systemic circulation. Previous investigations in sheep and rats show that this region of the brain has a crucial role in osmoregulatory vasopressin secretion and thirst. The effects of lesions of the lamina terminalis, studies of immediate-early gene expression and electrophysiological data show that all three regions of the lamina terminalis are involved in osmoregulation. There is considerable evidence that physiological osmoreceptors subserving vasopressin release are located in the dorsal cap region of the OVLT and possibly also around the periphery of the subfornical organ and in the MnPO. The circulating peptide hormones angiotensin II and relaxin also have access to peptide specific receptors (AT(1) and LGR7 receptors, respectively) in the subfornical organ and OVLT, and both angiotensin II and relaxin act on the subfornical organ to stimulate water drinking in the rat. Studies that combined neuroanatomical tracing and detection of c-fos expression in response to angiotensin II or relaxin suggest that both of these circulating peptides act on neurones within the dorsal cap of the OVLT and the periphery of the subfornical organ to stimulate vasopressin release.

Animals↗
PubMed2003

The sensory circumventricular organs of the mammalian brain.

The brain's three sensory circumventricular organs, the subfornical organ, organum vasculosum of the lamina terminalis and the area postrema lack a blood brain barrier and are the only regions in the brain in which neurons are exposed to the chemical environment of the systemic circulation. Therefore they are ideally placed to monitor the changes in osmotic, ionic and hormonal composition of the blood. This book describes their. General structure and relationship to the cerebral ventricles Regional subdivisions Vasculature and barrier properties Neurons, glia and ependymal cells Receptors, neurotransmitters, neuropeptides and enzymes Neuroanatomical connections Functions.

Animals↗
PubMed2003

The brain renin-angiotensin system: location and physiological roles.

Angiotensinogen, the precursor molecule for angiotensins I, II and III, and the enzymes renin, angiotensin-converting enzyme (ACE), and aminopeptidases A and N may all be synthesised within the brain. Angiotensin (Ang) AT(1), AT(2) and AT(4) receptors are also plentiful in the brain. AT(1) receptors are found in several brain regions, such as the hypothalamic paraventricular and supraoptic nuclei, the lamina terminalis, lateral parabrachial nucleus, ventrolateral medulla and nucleus of the solitary tract (NTS), which are known to have roles in the regulation of the cardiovascular system and/or body fluid and electrolyte balance. Immunohistochemical and neuropharmacological studies suggest that angiotensinergic neural pathways utilise Ang II and/or Ang III as a neurotransmitter or neuromodulator in the aforementioned brain regions. Angiotensinogen is synthesised predominantly in astrocytes, but the processes by which Ang II is generated or incorporated in neurons for utilisation as a neurotransmitter is unknown. Centrally administered AT(1) receptor antagonists or angiotensinogen antisense oligonucleotides inhibit sympathetic activity and reduce arterial blood pressure in certain physiological or pathophysiological conditions, as well as disrupting water drinking and sodium appetite, vasopressin secretion, sodium excretion, renin release and thermoregulation. The AT(4) receptor is identical to insulin-regulated aminopeptidase (IRAP) and plays a role in memory mechanisms. In conclusion, angiotensinergic neural pathways and angiotensin peptides are important in neural function and may have important homeostatic roles, particularly related to cardiovascular function, osmoregulation and thermoregulation.

Animals↗
PubMed2003

Circulating angiotensin II activates neurones in circumventricular organs of the lamina terminalis that project to the bed nucleus of the stria terminalis.

The aim of this study was to determine, in conscious rats, whether elevated concentrations of circulating angiotensin II activate neurones in both the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) that project to the bed nucleus of the stria terminalis (BNST). The strategy employed was to colocalize retrogradely transported cholera toxin B subunit (CTB) from the BNST, with elevated levels of Fos protein in response to angiotensin II. Circulating angiotensin II concentrations were increased by either intravenous infusion of angiotensin II or subcutaneous injection of isoproterenol. Neurones exhibiting Fos in response to angiotensin II were present in the subfornical organ, predominantly in its central core but with some also seen in its peripheral aspect, the dorsal and lateral margins of the OVLT, the supraoptic nucleus and the parvo- and magnocellular divisions of the paraventricular nucleus. Fos-labelling was not apparent in control rats infused with isotonic saline intravenously or injected with either CTB or CTB conjugated to gold particles (CTB-gold) only. Of the neurones in the subfornical organ that were shown by retrograde labelling to project to BNST, approximately 50% expressed Fos in response to isoproterenol. This stimulus also increased Fos in 33% of neurones in the OVLT that project to BNST. Double-labelled neurones were concentrated in the central core of the subfornical organ and lateral margins of the OVLT in response to increased circulating angiotensin II resulting from isoproterenol treatment. These data support a role for circulating angiotensin II acting either directly or indirectly on neurones in subfornical organ and OVLT that project to the BNST and provide further evidence of functional regionalization within the subfornical organ and the OVLT. The function of these pathways is yet to be determined; however, a role in body fluid homeostasis is possible.

Angiotensin II↗
PubMed2003

The effect of urocortin on ingestive behaviours and brain Fos immunoreactivity in mice.

The influence of urocortin (UCN) on ingestive behaviours and brain neural activity, as measured immunohistochemically by the presence of Fos protein, was determined in mice. Rat UCN was administered by continuous intracerebroventricular (ICV) or subcutaneous (SC) infusion. ICV infusion of UCN (100 ng/h, 14 days) transiently reduced daily food and water intakes (days 1-4) but body weight was reduced from day 2 into the post-infusion period. Sodium intake was reduced from day 3 to the end of infusion. SC infusion of UCN caused similar but smaller reductions in food and water intakes and body weight, without change in sodium intake. In separate experiments, Fos immunoreactivity was increased in several brain nuclei known to be involved in the control of body fluid and energy homeostasis, e.g. central nucleus of the amygdala, median preoptic nucleus, bed nucleus of the stria terminalis and arcuate nucleus. Increased Fos expression was similar for ICV and SC infusions when measured on days 2-3 or 6-7 of infusion. In conclusion, increases of brain activity by UCN may be associated with stimulation of adrenocorticotrophic hormone release and sympathetic nervous activity, but increases may also indicate suppression of ingestive behaviours by stimulating central inhibitory mechanisms located in areas known to control body fluid and energy homeostasis.

Animals↗
PubMed2002

Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat.

Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix. It may also influence body fluid balance by actions on the brain to stimulate thirst and vasopressin secretion. We mapped the sites in the brain that are activated by i.v. infusion of a dipsogenic dose of relaxin (25 microg/h) by immunohistochemically detecting Fos expression. Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished relaxin-induced water drinking, but did not prevent increased Fos expression in the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular subdivision of the paraventricular nucleus. In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10(-7) M) added to the perfusion medium caused marked and prolonged increase in neuronal activity. Most of these neurons also responded to 10(-7) M angiotensin II. The data indicate that blood-borne relaxin can directly stimulate neurons in the SFO to initiate water drinking. It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion. These two circumventricular organs that lack a blood-brain barrier may have regulatory influences on fluid balance during pregnancy in rats.

Angiotensin II↗
PubMed2002

The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat.

The identification of leptin and a range of novel anorectic and orexigenic peptides has focussed attention on the neural circuitry involved in the genesis of food intake and the reflex control of thermogenesis. Here, the neurotropic virus pseudorabies has been utilised in conjunction with the immunocytochemical localisation of a variety of neuroactive peptides and receptors to better define the pathways in the rat hypothalamus directed polysynaptically to the major thermogenic endpoint, brown adipose tissue. Infected neurones were detected initially in the stellate ganglion, then in the spinal cord followed by the appearance of third-order premotor neurones in the brainstem and hypothalamus. Within the hypothalamus these were present in the paraventricular nucleus, lateral hypothalamus, perifornical region, and retrochiasmatic nucleus. At slightly longer survival times virus-infected neurones appeared in the arcuate nucleus and dorsomedial hypothalamus. Neurones in the retrochiasmatic nucleus and in the adjacent lateral arcuate nucleus which project to the brown adipose tissue express cocaine- and amphetamine-regulated transcript, pro-opiomelanocortin and leptin receptors. Neurones in the lateral hypothalamus, a site traditionally associated with the promotion of feeding, project to brown adipose tissue and large numbers of these contained melanin-concentrating hormone and orexin A and B. These data provide part of an anatomical framework which subserves the regulation of energy expenditure.

Adipose Tissue, Brown↗
PubMed2001

Neurons in the lamina terminalis which project polysynaptically to the kidney express angiotensin AT1A receptor.

The retrograde transynaptic transport of pseudorabies virus was used in conjunction with hybridisation histochemistry for the angiotensin II AT1A receptor, to characterise neurons in the lamina terminalis projecting to the kidney. These data demonstrate that some neurons in the lamina terminalis, that project polysynaptically to the kidney, may be responsive to angiotensin II.

Animals↗
PubMed2001

A method for the identification of pseudorabies virus protein and angiotensin AT(1A) receptor mRNA expression in the same CNS neurons.

Neurotropic viruses have been used over the last 10 years to map the distribution of chains of synaptically connected neurons in the CNS. The peptide content of infected neurons has been determined in a number of cases immunohistochemically. However, it has been unclear whether specific mRNA can be assessed in virus-infected neurons. We have established a technique which enables the identification of viral protein and mRNA in the same neuron. In the present study pseudorabies virus retrogradely transported from the kidney was localised using immunohistochemistry and mRNA for the angiotensin II AT(1A) receptor was detected by hybridisation histochemistry. Virus protein was visualised using an immunohistochemical procedure with diaminobenzidine as the chromogen and the same sections were exposed to radioactively labelled ((35)S) riboprobes, hybridising the angiotensin II AT(1A) receptor. The combination of these two approaches resulted in the identification of neurons shown to project polysynaptically to the kidney and express AT(1A) mRNA. These data provide neuroanatomical support for previous physiological observations that ablation of the lamina terminalis and administration of losartan, the AT(1) receptor antagonist, blocks the inhibition of renal sympathetic nerve activity following centrally injected Ang II in rats and sheep [5].

Animals↗
PubMed2001

Efferent neural projections of angiotensin receptor (AT1) expressing neurones in the hypothalamic paraventricular nucleus of the rat.

Angiotensin II acts within the hypothalamic paraventricular nucleus (PVN) to help mediate a number of autonomic and endocrine responses. Evidence is sparse in regard to the particular neuronal cell groups that exhibit angiotensin II type 1 receptors within the PVN, and does not exist in relation to specified efferent neuronal populations in the nucleus. In the present experiments, retrogradely transported neuronal tracers were utilized in conjunction with immunohistochemistry using a well characterized polyclonal antibody raised against a decapeptide sequence at the carboxy terminus of the AT1 receptor, to determine whether it is preferentially distributed amongst different efferent populations within the PVN. The AT1 receptor is not associated with neurones in the PVN that project axons to the spinal cord, dorsomedial or ventrolateral medulla but coexists strongly with neurones in the anterior parvocellular division of the nucleus which direct axons to the median eminence. Such neurones often contain corticotropin releasing factor. These findings highlight the role that angiotensin II and AT1 receptors in the PVN may play in the mediation of responses to stress.

Animals↗
PubMed2001

Identification of efferent neural pathways from the lamina terminalis activated by blood-borne relaxin.

The ovarian hormone relaxin, in addition to its role in pregnancy, exerts an action on the brain to influence oxytocin and vasopressin secretion, water drinking, and cardiovascular function. Intravenous (i.v.) infusion of relaxin causes an acute water drinking response, confirming its role as a dipsogenic hormone. The aim of this study was to determine whether neurones in the lamina terminalis, which project to the hypothalamic paraventricular and supraoptic nuclei, are activated by elevated levels of circulating relaxin in conscious rats. Immunocytochemistry combined with retrograde neuronal tracing with cholera toxin B subunit conjugated to cholera toxin B (CTB-gold) was used to identify populations of neurones responding with elevated cells of Fos protein to i.v. relaxin administration and which project to these specific hypothalamic sites. Neurones exhibiting Fos were present in the outer parts of the subfornical organ (SFO), the dorsal part of the organum vasculosum (OVLT), the supraoptic nucleus and the paraventricular nucleus. These did not occur in control rats with i.v. infusions of isotonic saline. Approximately 90% of neurones concentrated in the outer parts of the SFO and in the dorsal OVLT showed both retrogradely transported CTB-gold and Fos in response to i.v. infusion of relaxin. These data support a role for relaxin acting on the brain to regulate body fluid and electrolyte homeostasis by activating neural pathways subserving water drinking, vasopressin and oxytocin secretion.

Animals↗
PubMed2001

Neural pathways from the lamina terminalis influencing cardiovascular and body fluid homeostasis.

1. The lamina terminalis, a region of the brain with a high concentration of angiotensin AT1 receptors, consists of three distinct nuclei, the median preoptic nucleus, the subfornical organ and organum vasculosum of the lamina terminalis (OVLT). These latter two regions lack a blood-brain and detect changes in plasma angiotensin (Ang) II concentration and osmolality. 2. Efferent neural pathways from the lamina terminalis to the hypothalamic paraventricular and supraoptic nuclei mediate vasopressin secretion in response to plasma hypertonicity and increased circulating levels of AngII. 3. Studies using the neurotropic virus pseudorabies, which undergoes retrograde transynaptic neuronal transport following injection into peripheral sites, show that neurons in the lamina terminalis have efferent polysynaptic neural connections to the peripheral sympathetic nervous system. Some of these neurons have been shown to have polysynaptic connections to the kidney and to express AT1 receptor mRNA. We propose that circulating AngII acts at AT1 receptors in the subfornical organ and OVLT to influence the sympathetic nervous system. It is likely that the neural pathway subserving this influence involves a synapse in the hypothalamic paraventricular nucleus. 4. The lamina terminalis may exert an inhibitory osmoregulatory influence on renin secretion by the kidney. This osmoregulatory influence may be mediated by inhibition of renal sympathetic nerve activity and appears to involve a central angiotensinergic synapse. 5. The lamina terminalis exerts an osmoregulatory influence on renal sodium excretion that is independent of the renal nerves and is probably hormonally mediated.

Angiotensin II↗
PubMed2001

Activation of kidney-directed neurons in the lamina terminalis by alterations in body fluid balance.

This study was undertaken to determine if neurons in the lamina terminalis, previously identified as projecting to the kidney (35), were responsive to alterations in stimuli associated with fluid balance homeostasis. Neurons in the lamina terminalis projecting to the kidney were identified by the retrograde transynaptic transport of Bartha's strain of pseudorabies virus in anesthetized rats. Rats were also exposed to 24-h water deprivation, intravenous hypertonic saline, or intracerebroventricular ANG II. To determine if "kidney-directed" neurons were activated following each stimulus, brain sections that included the lamina terminalis were examined immunohistochemically for viral antigen and Fos protein. With the exception of ANG II in the subfornical organ, all regions of the lamina terminalis contained neurons that were significantly activated by water deprivation, hypertonic saline, and ANG II. These results provide evidence for a neural substrate, which may underpin some of the effects of hypertonic saline and ANG II on renal function thought to be mediated through the lamina terminalis.

Angiotensin II↗
PubMed2001

Brain angiotensin and body fluid homeostasis.

Angiotensinogen, the precursor molecule of the peptides angiotensin I, II, and III, is synthesized in the brain and the liver. Evidence is reviewed that angiotensin II, and possibly angiotensin III, that are generated within the brain act within neural circuits of the central nervous system to regulate body fluid balance. Immunohistochemical studies in the rat brain have provided evidence of angiotensin-containing neurons, especially in the hypothalamic paraventricular nucleus, subfornical organ, periventricular region, and nucleus of the solitary tract, as well as in extensive angiotensin-containing fiber pathways. Angiotensin immunoreactivity is observed by electron microscope in synaptic vesicles in several brain regions, the most prominent of these being the central nucleus of the amygdala. Neurons in many parts of the brain (lamina terminalis, paraventricular and parabrachial nuclei, ventrolateral medulla, and nucleus of the solitary tract) known to be involved in the regulation of body fluid homeostasis exhibit angiotensin receptors of the AT(1) subtype. Pharmacological studies in several species show that intracerebroventricular administration of AT(1) receptor antagonist drugs inhibit homeostatic responses to the central administration of hypertonic saline, intravenous infusion of the hormone relaxin, or thermal dehydration. Responses affected by centrally administered AT(1) antagonists are water drinking, vasopressin secretion, natriuresis, increased arterial pressure, reduced renal renin release, salt hunger, and thermoregulatory adjustments. We conclude that angiotensinergic neural pathways in the brain probably have an important homeostatic function, especially in regard to osmoregulation and thermoregulation, and the maintenance of arterial pressure.

Angiotensin II↗
PubMed2000

Fos immunoreactivity in the lamina terminalis of adrenalectomized rats and effects of angiotension II type 1 receptor blockade or deoxycorticosterone.

Neural activity, as measured immunohistochemically by the presence of Fos protein, was determined in the lamina terminalis, a thin strip of tissue forming the anterior wall of the third brain ventricle, after adrenalectomy. Several weeks after surgery, the adrenalectomized rats were maintained with access to water and a low sodium diet for five days. In addition, hypertonic (0.5M) NaCl solution was available for the entire five-day period (sodium available) or only during the first four days (sodium unavailable). The number of neurons expressing Fos, determined at the end of the fifth day, was increased in the adrenalectomized rats with or without NaCl solution to drink. Fos activity in the median preoptic nucleus was increased only in adrenalectomized rats without access to NaCl solution. Treatment of adrenalectomized rats with the sodium-retaining mineralocorticoid hormone, deoxycorticosterone, at the end of the fourth day, decreased Fos expression in the subfornical organ and the organum vasculosum of the lamina terminalis when NaCl solution was available but not when the NaCl solution was unavailable. In the adrenalectomized rats with NaCl solution available, mineralocorticoid treatment decreased both urinary sodium excretion and daily sodium intake. Brain nuclei in the lamina terminalis also became activated in intact rats made sodium deplete by treatment with the diuretic, furosemide. Relative to sodium-deplete intact rats, however, sodium-deplete adrenalectomized rats had a greater number of neurons expressing Fos in the organum vasculosum. Treatment of sodium-deplete rats, adrenalectomized or intact, with the angiotensin II-type 1 receptor antagonist, ZD7155, decreased sodium intake and Fos expression in the subfornical organ but not in the organum vasculosum of the lamina terminalis or median preoptic nucleus. In conclusion, the results demonstrated that activation of the brain nuclei located in the lamina terminalis of adrenalectomized rats was primarily related to sodium deficit and not to the absence of the mineralocorticoid hormones, although the adrenal hormones may have a role in limiting the activation of organum vasculosum of the lamina terminalis during sodium depletion. Furthermore, the results obtained with the administration of the angiotensin receptor antagonist are consistent with the proposal that sodium appetite of the sodium-deplete rat, adrenalectomized or intact, is mediated by circulating angiotensin II acting in the subfornical organ.

Adrenalectomy↗