Morphology and function of capillary networks in subregions of the rat tuber cinereum

Shaver, Steven W.; Pang, Judith J.; Wainman, Dan S.; Wall, Katharine M.; Gross, Paul M.

doi:10.1007/bf00319366

Cited by 82 publications

(54 citation statements)

References 38 publications

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“…However, an issue that must be taken into consideration is how leptin gains access to central feeding circuits protected behind the BBB. It has been suggested that leptin directly accesses the ARC through a leaky BBB; however, anatomical studies have clearly demonstrated that the ARC has an intact BBB as it does not contain type III fenestrated capillaries (45). Although a saturable blood-tobrain transport system for leptin has been demonstrated (2), it is not clear what concentrations of transported substances are delivered to their target normally protected by the BBB.…”

Section: Discussionmentioning

confidence: 99%

The subfornical organ: a central nervous system site for actions of circulating leptin

Smith

Chambers²,

Price³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Adipose tissue plays a critical role in energy homeostasis, secreting adipokines that control feeding, thermogenesis, and neuroendocrine function. Leptin is the prototypic adipokine that acts centrally to signal long-term energy balance. While hypothalamic and brain stem nuclei are well-established sites of action of leptin, we tested the hypothesis that leptin signaling occurs in the subfornical organ (SFO). The SFO is a circumventricular organ (CVO) that lacks the normal blood-brain barrier, is an important site in central autonomic regulation, and has been suggested to have a role in modulating peripheral signals indicating energy status. We report here the presence of mRNA for the signaling form of the leptin receptor in SFO and leptin receptor localization by immunohistochemistry within this CVO. Central administration of leptin resulted in phosphorylation of STAT3 in neurons of SFO. Whole cell currentclamp recordings from dissociated SFO neurons demonstrated that leptin (10 nM) influenced the excitability of 64% (46/72) of SFO neurons. Leptin was found to depolarize the majority of responsive neurons with a mean change in membrane potential of 7.3 Ϯ 0.6 mV (39% of all SFO neurons), while the remaining cells that responded to leptin hyperpolarized (Ϫ6.9 Ϯ 0.7 mV, 25% of all SFO neurons). Similar depolarizing and hyperpolarizing effects of leptin were observed in recordings from acutely prepared SFO slice preparations. Leptin was found to influence the same population of SFO neurons influenced by amylin as three of four cells tested for the effects of bath application of both amylin and leptin depolarized to both peptides. These observations identify the SFO as a possible central nervous system location, with direct access to the peripheral circulation, at which leptin may act to influence hypothalamic control of energy homeostasis. circumventricular organ; hypothalamus ADIPOSE TISSUE PLAYS A CRITICAL role in energy homeostasis, secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. Leptin, a 16 kDa peptide, is the prototypic adipokine that has been shown to be an important afferent signal regulating body weight. A missense mutation in the ob gene (the gene that encodes leptin) in the ob/ob mouse, results in a markedly obese phenotype that is normalized by both systemic and central leptin administration (9,19,37). Leptin administration also has been shown to dose-dependently decrease body weight, preferentially reducing body fat while sparing lean tissue in both ob/ob and wild-type mice (18,19). Plasma leptin levels reflect both energy stores and acute energy balance. Circulating leptin decreases food intake and increases energy expenditure through activation of receptors in hypothalamic and brain stem neurons (16) .The leptin receptor, encoded by the Ob-R gene, was isolated from choroid plexus by expression cloning and is a member of the cytokine family (48). Although five leptin receptor isoforms have been identified (Ob-Ra to Ob-Re), only the long form of the rece...

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Section: Discussionmentioning

confidence: 99%

The subfornical organ: a central nervous system site for actions of circulating leptin

Smith

Chambers²,

Price³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The arcuate is characterized by receptors for peripherally active hormones, including ghrelin (Cowley et al, 2003;Mondal et al, 2005). It has been reported that the blood-brain barrier border could actually lie at the area between the median eminence and the distal part of the arcuate, indicating that the proximal arcuate could be exposed to circulating neuroactive substances (Shaver et al, 1992). Recently, a reciprocal linkage between the ventromedial arcuate to the SCN was established by means of anterograde and retrograde tracing techniques (Yi et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Effects on the Circadian System of Mice

Yannielli

Molyneux²,

Harrington³

et al. 2007

J. Neurosci.

120

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The orexigenic peptide ghrelin stimulates both food intake and growth hormone release and is synthesized in the stomach and in hypothalamic areas involved in feeding control. The suprachiasmatic nuclei of the hypothalamus (SCN) control most circadian rhythms, although there is evidence that some oscillators, such as food-entrainable oscillators, can drive activity rhythms even after SCN ablation. Ghrelin levels exhibit a circadian rhythm and closely follow feeding schedules, making this peptide a putative candidate for food-related entraining signals. We examined the response of the SCN to ghrelin treatments in vitro, by means of electrophysiological and bioluminescence recordings, and in vivo, by assessing effects on the phase of locomotor activity rhythms. Ghrelin applied at circadian time 6 in vitro to cultured SCN slices induced an ϳ3 h phase advance. In addition, ghrelin phase advanced the rhythm of PER2::LUC (Period2::Luciferase) expression in cultured SCN explants from mPer2Luc transgenic mice. In vivo, intraperitoneal administration of ghrelin or a synthetic analog, growth hormone-releasing protein-6 (GHRP-6), to ad libitum fed animals failed to alter circadian phase. When injected after 30 h of food deprivation, GHRP-6 induced a phase advance compared with saline-injected animals. These results indicate that ghrelin may play a role in the circadian system by exerting a direct action on the SCN and that the system as a whole may become sensitive to ghrelin and other feeding-related neuropeptides under conditions of food restriction.

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“…Because the median eminence was labeled with 125 I-leptin, it is likely that leptin reaches the cells in the arcuate nucleus via the median eminence, a structure that belongs to the circumventricular organs, i.e., regions known to lack a BBB. Furthermore, there is evidence that the ventral but not the dorsal part of the arcuate nucleus lacks a BBB (Shaver et al, 1992). It is possible therefore that the leptin secreted exclusively from adipocytes is transported to the brain via the general circulation and acts on LR located in the ventromedial arcuate nucleus devoid of BBB.…”

Section: Discussionmentioning

confidence: 99%

Leptin Receptor Immunoreactivity in Chemically Defined Target Neurons of the Hypothalamus

et al. 1998

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The adipose tissue-derived hormone leptin regulates body weight homeostasis by decreasing food intake and increasing energy expenditure. The weight-reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor (LR) in the hypothalamus. We have used immunohistochemistry to localize LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum against a portion of the intracellular domain of LR that is common to all LR isoforms. The antiserum recognized the short and long isoforms of LR in transfected hematopoietic BaF3 cells. To examine the chemical nature of target cells for leptin, direct double-labeling immunofluorescence histochemistry was applied. The results show extensive distribution of LR-like immunoreactivity (LR-LI) in the brain with positively stained cells present, e.g., in the choroid plexus, cerebral cortex, hippocampus, thalamus, and hypothalamus. In the hypothalamus, strongly LR-IR neurons were present in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), periventricular nucleus, arcuate nucleus, and lateral hypothalamus. Weaker LR-IR neurons were also demonstrated in the lateral and medial preoptic nuclei, suprachiasmatic nucleus, ventromedial and dorsomedial nuclei, and tuberomammillary nucleus. Confocal laser scanning microscopy showed LR-LI in the periphery of individual cells. In magnocellular neurons of the SON and PVN, LR-LI was demonstrated in vasopressin-and oxytocin-containing neurons. In parvocellular neurons of the PVN, LR-LI was demonstrated in many corticotropin-releasing hormone-containing neurons. LR-IR neurons were mainly seen in the ventromedial aspect of the arcuate nucleus, where LR-LI co-localized with neuropeptide Y. In the ventrolateral part of the arcuate nucleus, LR-LI was present in many large adrenocorticotropic hormone-IR proopiomelanocortin-containing neurons and in a few galanin-, neurotensin-, and growth hormone-releasing hormonecontaining neurons. In the dorsomedial arcuate nucleus, few tyrosine hydroxylase (dopamine)-containing neurons were seen to have LR-LI. Melanin-concentrating hormone-containing neurons in the lateral hypothalamus had LR-LI. Based on the immunohistochemical results, possible interactions of leptin with brain mechanisms are discussed.

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Morphology and function of capillary networks in subregions of the rat tuber cinereum

Cited by 82 publications

References 38 publications

The subfornical organ: a central nervous system site for actions of circulating leptin

The subfornical organ: a central nervous system site for actions of circulating leptin

Ghrelin Effects on the Circadian System of Mice

Leptin Receptor Immunoreactivity in Chemically Defined Target Neurons of the Hypothalamus

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