Astrocytes Control Food Intake by Inhibiting AGRP Neuron Activity via Adenosine A1 Receptors

Yang, Liang; Qi, Yong; Yang, Yunlei

doi:10.1016/j.celrep.2015.04.002

Cited by 208 publications

(214 citation statements)

References 50 publications

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“…10A). In addition, we infused ghrelin as a positive control because intra-Arc injection of ghrelin significantly increases food intake during the light period (Yang et al, 2015). We confirmed that intra-Arc injection of 0.7 mM ghrelin increased food intake (86 Ϯ 42 mg for vehicle control, 396 Ϯ 37 mg for ghrelin, p Ͻ 0.0001; Fig.…”

Section: Are P2x4 Receptors Involved In the Control Of Feeding?supporting

confidence: 67%

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P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus

Xu¹,

Bernstein

Wong

et al. 2016

J. Neurosci.

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P2X4 receptors are ATP-gated cation channels that are widely expressed in the nervous system. To identify P2X4 receptor-expressing cells, we generated BAC transgenic mice expressing tdTomato under the control of the P2X4 receptor gene (P2rx4). We found sparse populations of tdTomato-positive neurons in most brain areas with patterns that matched P2X4 mRNA distribution. tdTomato expression within microglia was low but was increased by an experimental manipulation that triggered microglial activation. We found surprisingly high tdTomato expression in the hypothalamic arcuate nucleus (Arc) (i.e., within parts of the neural circuitry controlling feeding). Immunohistochemistry and genetic crosses of P2rx4 tdTomato mice with cell-specific GFP reporter lines showed that the tdTomato-expressing cells were mainly AgRP-NPY neurons and tanycytes. There was no electrophysiological evidence for functional expression of P2X4 receptors on AgRP-NPY neuron somata, but instead, we found clear evidence for functional presynaptic P2X4 receptor-mediated responses in terminals of AgRP-NPY neurons onto two of their postsynaptic targets (Arc POMC and paraventricular nucleus neurons), where ATP dramatically facilitated GABA release. The presynaptic responses onto POMC neurons, and the expression of tdTomato in AgRP-NPY neurons and tanycytes, were significantly decreased by food deprivation in male mice in a manner that was partially reversed by the satiety-related peptide leptin. Overall, we provide well-characterized tdTomato reporter mice to study P2X4-expressing cells in the brain, new insights on feeding-related regulation of presynaptic P2X4 receptor responses, and the rationale to explore extracellular ATP signaling in the control of feeding behaviors.

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Section: Are P2x4 Receptors Involved In the Control Of Feeding?supporting

confidence: 67%

“…We used procedures based on published work (Wong et al, 2015;Yang et al, 2015). Mice (8-to 10-week old; male) were anesthetized with isoflurane (induction at 5%, maintenance at 1%-2.5% v/v) and placed on a stereotaxic apparatus.…”

Section: Methodsmentioning

confidence: 99%

P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus

Xu¹,

Bernstein

Wong

et al. 2016

J. Neurosci.

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show abstract

“…Leptin signaling in astrocytes was also recently shown to play an active role in the hypothalamic control of feeding . Recently, astrocytes were shown to control food intake by inhibiting AgRP neuron activity (Yang et al 2015), which suggests astrocytes are indirectly able to promote fertility as restraining AgRP neurons would presumably facilitate GNRH drive, as mentioned previously. Furthermore, Sandau and coworkers demonstrated that the synaptic cell adhesion molecule, SynCAM1, mediates astrocyte-to-GNRH neuron adhesiveness in the mouse hypothalamus (Sandau et al 2011b), and it was shown that astrocyte-to-GNRH neuron adhesiveness via SynCAM1 is important in the control of female sexual development.…”

Section: Astroglial Cellsmentioning

confidence: 60%

Neuroendocrine integration of nutritional signals on reproduction

Evans

Anderson

2017

Journal of Molecular Endocrinology

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Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GNRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this 'metabolic control of fertility'. However, the neural circuitry through which they act to exert their control over GNRH drive remains incompletely understood. With the advent of Cre-LoxP technology, it has become possible to perform targeted gene-deletion and gene-rescue experiments and thus test the functional requirement and sufficiency, respectively, of discrete hormone-neuron signaling pathways in the metabolic control of reproductive function. This review discusses the findings from these investigations, and attempts to put them in context with what is known from clinical situations and wild-type animal models. What emerges from this discussion is clear evidence that the integration of nutritional signals on reproduction is complex and highly redundant, and therefore, surprisingly difficult to perturb. Consequently, the deletion of individual hormone-neuron signaling pathways often fails to cause reproductive phenotypes, despite strong evidence that the targeted pathway plays a role under normal physiological conditions. Although transgenic studies rarely reveal a critical role for discrete signaling pathways, they nevertheless prove to be a good strategy for identifying whether a targeted pathway is absolutely required, critically involved, sufficient or dispensable in the metabolic control of fertility.

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“…All the experiments were performed in the early light period with brain slices prepared at 09:00. Acute brain slices that include hypothalamic ARC and VMH were prepared as described in our previous work (Yang et al, , 2015. Briefly, mice were deeply anesthetized with isoflurane and decapitated.…”

Section: Methodsmentioning

confidence: 99%

Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors

Yang

2015

J. Neurosci.

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It remains largely unknown whether and how hunger states control activity-dependent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). We here report that both LTP and LTD of excitatory synaptic strength within the appetite control circuits residing in hypothalamic arcuate nucleus (ARC) behave in a manner of hunger states dependence and cell type specificity. For instance, we find that tetanic stimulation induces LTP at orexigenic agouti-related protein (AgRP) neurons in ad libitum fed mice, whereas it induces LTD in food-deprived mice. In an opposite direction, the same induction protocol induces LTD at anorexigenic pro-opiomelanocortin (POMC) neurons in fed mice but weak LTP in deprived mice. Mechanistically, we also find that food deprivation increases the expressions of NR2C/NR2D/NR3-containing NMDA receptors (NMDARs) at AgRP neurons that contribute to the inductions of LTD, whereas it decreases their expressions at POMC neurons. Collectively, our data reveal that hunger states control the directions of activity-dependent synaptic plasticity by switching NMDA receptor subpopulations in a cell type-specific manner, providing insights into NMDAR-mediated interactions between energy states and associative memory.

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Astrocytes Control Food Intake by Inhibiting AGRP Neuron Activity via Adenosine A1 Receptors

Cited by 208 publications

References 50 publications

P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus

P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus

Neuroendocrine integration of nutritional signals on reproduction

Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors

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