Induction of Fos-like immunoreactivity in rat oxytocin neurons following insulin injections

Neurohypophyseal secretion of oxytocin and vasopressin is elevated in response to decreased systemic glucose availability. In these studies, dual-label immunocytochemistry was used to identify hypothalamic neuropeptidergic magnocellular neurones that are transcriptionally activated in response to glucose substrate imbalance. Two h after i.p. injection of the glucose antimetabolite, 2-deoxy-D-glucose (2DG), or the vehicle, saline, groups of adult male rats were anaesthetized by i.p. injection with sodium pentobarbital and killed by transcardial perfusion. Sections (25 microm) through anterior and tuberal levels of the hypothalamus were processed for nuclear Fos- and cytoplasmic neuropeptide immunoreactivity (-ir). A high proportion of oxytocin-ir neurones in the supraoptic, paraventricular, and adjunct structures, including the anterior commissural, periventricular magnocellular, posterior perifornical, recurrent supraoptic, medial forebrain, and circular nuclei, were colabelled for nuclear Fos-ir following administration of 2DG. Large numbers of vasopressin neurones in the supraoptic, circular, posterior perifornical, and medial forebrain nuclei, and posterior magnocellular division and posterior subnucleus of the paraventricular nucleus were also immunostained for Fos in rats injected with the antimetabolite. These results show that decreased glucose metabolism is a stimulus for activation of the Fos stimulus-transcription cascade within oxytocin-and vasopressin-immunopositive neurones in several hypothalamic loci, findings that reflect activation of the Fos-stimulus transcription cascade within large proportions of these cell populations during this metabolic challenge. These data suggest that both peripheral hormonal and central modulatory functions of these neuropeptidergic neurones may be influenced by cellular glucose availability.

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 77%

Oxytocin and Vasopressin Neurones in Principal and Accessory Hypothalamic Magnocellular Structures Express Fos‐Immunoreactivity in Response to Acute Glucose Deprivation

Briski

Brandt

2000

“…Although Fos protein has been widely used as a marker for neuronal activation, its lack of expression does not necessarily exclude changes in neural activity as observed in some conditions, and increased spike activity is not invariably linked to Fos expression . It appears that insulin might not induce the expected rapid expression of Fos (ie, 60‐90 minutes) because Griffond et al reported that, at 1 hour after insulin i.p. (20 mg kg ‐1 ), there was little expression of Fos in PVN oxytocin cells.…”

Section: Discussionmentioning

confidence: 99%

“…Amongst these, the insulin receptor (InsR) is abundantly expressed in the supraoptic nucleus (SON), which exclusively contains magnocellular oxytocin and vasopressin cells, and i.p. administration of insulin induces the expression of Fos protein in parvo‐ and magnocellular oxytocin cells of the paraventricular nucleus in rats . Explants of the hypothalamo‐neurohypophysial system, including the SON and its projections to the posterior pituitary, release oxytocin and vasopressin in response to direct application of insulin, and central administration of insulin increases peripheral secretion of oxytocin in mice by a direct action on oxytocin cells …”

Section: Introductionmentioning

confidence: 99%

Peripheral insulin administration enhances the electrical activity of oxytocin and vasopressin neurones in vivo

Paiva

Leng

2020

Oxytocin neurones are involved in the regulation of energy balance through diverse central and peripheral actions and, in rats, they are potently activated by gavage of sweet substances. Here, we test the hypothesis that this activation is mediated by the central actions of insulin. We show that, in urethane‐anaesthetised rats, oxytocin cells in the supraoptic nucleus show prolonged activation after i.v. injections of insulin, and that this response is greater in fasted rats than in non‐fasted rats. Vasopressin cells are also activated, although less consistently. We also show that this activation of oxytocin cells is independent of changes in plasma glucose concentration, and is completely blocked by central (i.c.v.) administration of an insulin receptor antagonist. Finally, we replicate the previously published finding that oxytocin cells are activated by gavage of sweetened condensed milk, and show that this response too is completely blocked by central administration of an insulin receptor antagonist. We conclude that the response of oxytocin cells to gavage of sweetened condensed milk is mediated by the central actions of insulin.

“…Identification of stimulus‐induced Fos protein expression in activated neurones offers an excellent anatomical technique for the integration of physiology and behaviour (16, 17). In this context, the induction of Fos protein elicited by insulin‐induced hypoglycaemia has been reported (18, 19). Anand, Oomura and other researchers have provided evidence for the existence of glucose responsiveness in a number of hypothalamic nuclei including arcuate nucleus, VMH and LHA (20–22) Of relevance to the present study is the observation that glucose‐responsive neurones respond with increased activation to the local administration of insulin (13).…”

mentioning

confidence: 99%

Insulin and Glucose Administration Stimulates Fos Expression in Neurones of the Paraventricular Nucleus That Project to Autonomic Preganglionic Structures

Carrasco

Portillo

Larsen

et al. 2001

Insulin and glucose play a key role in the control of body energy homeostasis. However, the anatomical organization of the network of central insulin and glucose sensitive areas is still unclear. In the present study, we used a multiple-labelling technique combining retrograde tracing and Fos-like immunohistochemistry, to analyse the anatomical projections from hypothalamic neurones activated by the combined stimulus of insulin and glucose. After intraperitoneal injections of a bolus of insulin plus glucose, Fos-like immunoreactive neurones were observed in the paraventricular nucleus (PVN), ventromedial and arcuate nuclei, as well as the lateral hypothalamic area. In addition, neurones projecting to the autonomic preganglionic levels in the brainstem and spinal cord potentially involved in the control of glucose metabolism were identified by injections of fluorochrome tracers. Thus, Fluorogold was injected into the intermediolateral cell column of the lower spinal cord and Fast Blue was injected into the dorsal motor nucleus of the vagus. Perikarya of descending neurones were detected chiefly in the dorsal, medial and lateral parvocellular subnuclei and also in the posterior magnocellular subnucleus of the PVN. In contrast, insulin-glucose activated neurones in the PVN were observed mainly in the medial parvocellular and posterior magnocellular subnuclei. Fluorogold/Fos double-labelled neurones were only observed in the ventral zone of the medial parvocellular subnucleus. These data indicate that, within the PVN, there could be neurones responding to insulin-glucose administration, which are involved in the sympathetic control of the classical regulatory structures of body energy homeostasis, such as the liver and pancreas, and which could play a role in the output of the neuronal circuitry controlling food intake.