The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes

Feng, Cheng‐Yuan; Wiggins, Larisa M.; Bartheld, Christopher S. von

doi:10.1523/jneurosci.5018-10.2011

Cited by 19 publications

(19 citation statements)

References 74 publications

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“…One possibility is that MCH translocates into the neuropil through tanycytes, which are specialized ependymal cells lining the base of the lateral and third cerebral ventricles. For example, radiolabeled nerve growth factor injected into the CSF has been shown to translocate from the CSF through tanycytes and accumulate in the locus coeruleus (Feng et al, 2011). Moreover, the anorectic adipokine, leptin, is trafficked from the median eminence to mediobasal hypothalamic neurons via tanycyte-mediated transport into CSF (Balland et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone

et al. 2018

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Classical mechanisms through which brain-derived molecules influence behavior include neuronal synaptic communication and neuroendocrine signaling. Here we provide evidence for an alternative neural communication mechanism that is relevant for food intake control involving cerebroventricular volume transmission of the neuropeptide melanin-concentrating hormone (MCH). Results reveal that the cerebral ventricles receive input from approximately one-third of MCH-producing neurons. Moreover, MCH cerebrospinal fluid (CSF) levels increase prior to nocturnal feeding and following chemogenetic activation of MCH-producing neurons. Utilizing a dual viral vector approach, additional results reveal that selective activation of putative CSF-projecting MCH neurons increases food intake. In contrast, food intake was reduced following immunosequestration of MCH endogenously present in CSF, indicating that neuropeptide transmission through the cerebral ventricles is a physiologically relevant signaling pathway for energy balance control. Collectively these results suggest that neural-CSF volume transmission signaling may be a common neurobiological mechanism for the control of fundamental behaviors.

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Section: Discussionmentioning

confidence: 99%

Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone

et al. 2018

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“…Thus, CSF ghrelin appears to have a higher accessibility, as compared to other hormones, and quickly access to different brain areas. Interestingly, it has been shown that noradrenergic neurons of the avian LoC accumulate CSF components, which are initially endocytosed and transcytosed by ependymal cells (Feng et al, 2011). This uptake of molecules from the CSF is highly selective as internalizes nerve growth factor and urotensin-1, but not other neurotrophic factors (Feng et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, it has been shown that noradrenergic neurons of the avian LoC accumulate CSF components, which are initially endocytosed and transcytosed by ependymal cells (Feng et al, 2011). This uptake of molecules from the CSF is highly selective as internalizes nerve growth factor and urotensin-1, but not other neurotrophic factors (Feng et al, 2011). Here we report that fluorescein-IR cells are present in the LoC, which presumably lacks GHSR-1a (Zigman et al, 2006, Perello et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid

Cabral¹,

Fernández²,

Perelló³

2013

Neuroscience

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Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal trough the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner.

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“…Tanycytes are known to extract different substances from the CSF, including glucose, glutamate, neuropeptides, NGF, and transforming growth factors. After intracellular transport, these substances can be released from tanycyte processes to adjacent neurons, thus contributing to intercellular signaling (Ugrumov and Mitskevich, ; Rodriguez et al, ; Feng et al, ). The fact that not all ependymal cells stained positive for fetuin‐A further supports an active and controlled process, rather than nonspecific transport of fetuin‐A over the CSF brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Fetuin‐A in the developing brain

Elsas¹,

Sellhaus²,

Herrmann³

et al. 2012

Developmental Neurobiology

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The serum protein fetuin-A is essential for mineral homeostasis and shows immunomodulatory functions, for example by binding to TGF superfamily proteins. It proved neuroprotective in a rat stroke model and reduced lethality after systemic lipopolysaccharide challenge in mice. Serum fetuin-A concentrations are highest during intrauterine life. Different species show intrauterine cerebral fetuin-A immunoreactivity, suggesting a contribution to brain development. We therefore aimed at specifying fetuin-A immunoreactivity in brains of newborn rats (age P0-P28) and human neonates (20-40 weeks of gestation). In humans and rats, fetuin-A was found in cortex, white matter, subplate, hippocampus, subventricular zone, and ependymal cells which supports a global role for brain function. In rats, overall fetuin-A immunoreactivity decreased with age. At P0 fetuin-A immunoreactivity affected most brain structures. Thereafter, it became increasingly restricted to distinct cells of the hippocampus, cingular gyrus, periventricular stem cell layer, and ependyma. In ependymal cells the staining pattern complied with active transependymal transport from cerebrospinal fluid. Double immunofluorescence studies revealed colocalization with NeuN (mature neurons), beta III tubulin (immature neurons), GFAP (astrocytes), and CD68 (activated microglia). This points to a role of fetuin-A in different brain functional systems. In human neonatal autopsy cases, frequently affected from severe neurological and non-neurological diseases, fetuin-A immunoreactivity was heterogeneous and much less associated with age than in healthy tissues studied earlier, suggesting an impact of exogeneous noxious factors on fetuin-A regulation. Further research on the role of fetuin-A in the neonatal brain during physiological and pathological conditions is recommended.

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The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes

Cited by 19 publications

References 74 publications

Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone

Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone

Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid

Fetuin‐A in the developing brain

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