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Article
Role of Astrocytes in Leptin Signaling
To test the hypothesis that astrocytic leptin signaling induces an overall potentiation of the neuronal response to leptin, we generated a new line of astrocyte-specific leptin receptor knockout (ALKO-Δ1) mice...
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Article
Sleep Fragmentation Has Differential Effects on Obese and Lean Mice
Chronic sleep fragmentation (SF), common in patients with sleep apnea, correlates with the development of obesity. We hypothesized that SF differentially affects neurobehavior in lean wild-type (WT) and obese ...
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Article
Hypersomnolence and Reduced Activity in Pan-Leptin Receptor Knockout Mice
Excessive obesity correlates with hypersomnolence and impaired cognitive function, presumably induced by metabolic factors and cytokines. Production of the adipokine leptin correlates with the amount of adipos...
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Article
Saturable Leptin Transport Across the BBB Persists in EAE Mice
We have shown that mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, have upregulated leptin receptor expression in reactive astrocytes of the hippocampus, a region invo...
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Article
Protective Role of Astrocytic Leptin Signaling Against Excitotoxicity
Both proconvulsive and anticonvulsive roles of leptin have been reported, suggesting cell-specific actions of leptin in different models of seizure and epilepsy. The goal of our study was to determine the regu...
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Article
Upregulation of Astrocytic Leptin Receptor in Mice with Experimental Autoimmune Encephalomyelitis
The detrimental role of leptin in experimental autoimmune encephalomyelitis (EAE) is opposite to its neuroprotective role in other neuropathologies. We hypothesize that a shifted cellular distribution of lepti...
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Article
Blood-Borne Metabolic Factors in Obesity Exacerbate Injury-Induced Gliosis
Reactive gliosis, a sign of neuroinflammation, has been observed in mice with adult-onset obesity as well as CNS injury. The hypothesis that obesity-derived metabolic factors exacerbate reactive gliosis in res...
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Article
Potential Protective Role of IL15Rα During Inflammation
We have shown that TNFα specifically activates the interleukin-15 (IL15) system in cerebral endothelial cells composing the blood–brain barrier. To determine the functions of cerebral IL15 signaling in inflamm...
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Article
Astrocytes Modulate Distribution and Neuronal Signaling of Leptin in the Hypothalamus of Obese A vy Mice
We tested the hypothesis that astrocytic activity modulates neuronal uptake and signaling of leptin in the adult-onset obese agouti viable yellow (A vy )...
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Article
IL-15 Receptor Deletion Results in Circadian Changes of Locomotor and Metabolic Activity
Interleukin-15 (IL-15) is a cytokine produced in the normal brain that acts on its specific receptor IL-15Rα and co-receptors IL-2Rβ and IL-2Rγ in neuronal cells. The functions of the cerebral IL-15 system, ho...
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Article
The Cdk5/p35 Kinases Modulate Leptin-Induced STAT3 Signaling
Cyclin-dependent kinase (Cdk) 5 is ubiquitously expressed in the brain and plays an essential role in central nervous system development and synaptic plasticity. The p35 kinase is a neuronal specific activator...
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Article
A Diffusion Barrier Between the Area Postrema and Nucleus Tractus Solitarius
The blood–brain barrier (BBB) is a structural and functional barrier that prevents free exchange of circulating substances with the brain, where the endothelial cells of microvessels are joined by tight juncti...
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Article
Unexpected Amplification of Leptin-Induced Stat3 Signaling by Urocortin: Implications for Obesity
Cooperativity among ingestive peptides reflects attempts by the body to finely control its weight. Urocortin, like leptin, is a potent suppressor of food intake, and they interact at the blood–brain barrier (B...
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Article
Urocortin trafficking in cerebral microvessel endothelial cells
Urocortin, a potent peptide inhibitor of feeding behavior, can enter the brain from blood by leptin-facilitated permeation across the blood-brain barrier. Here, we show in cultured RBE4 cerebral microvessel en...
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Article
Upregulation of p55 and p75 receptors mediating TNF-α transport across the injured blood-spinal cord barrier
Tumor necrosis factor (TNF-α) is involved in the inflammation and tissue regeneration occurring after spinal cord injury (SCI). This study tests the specific role of p55 and p75 receptors in mediating the tran...
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Article
Circulating TGF-β1 does not cross the intact blood-brain barrier
Transforming growth factor-β (TGF-β) from the periphery can cross the disrupted blood-brain barrier (BBB) to exert neuroprotective effects on the brain. Here, we quantify its permeation across the normal mouse...
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Article
Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier
Glucagon-like peptide-1 (GLP-1) reduces insulin requirement in diabetes mellitus and promotes satiety. GLP-1 in the periphery (outside the CNS) has been shown to act on the brain to reduce food ingestion. As G...