scholarly journals SAT-602 Hypothalamic P75 Neurotrophin Receptor Regulates Homeostatic Feeding and Food Anticipation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Brandon Podyma ◽  
Dove Johnson ◽  
Laura Sipe ◽  
Katherine Battin ◽  
Parks Remcho ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Energy Homeostasis ◽  
Neural Circuits ◽  
Time Of Day ◽  
Energy Deficit ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Driving Time ◽  
Neurotrophin Signaling

Abstract Proper circadian alignment of feeding behavior is necessary to prevent metabolic disease, and thus it is imperative to identify the neural circuits and molecular players that coordinate energy homeostasis. Neurotrophin signaling has been implicated in both metabolic and circadian processes, thereby representing a good candidate for regulating neural circuits driving time-of-day dependent feeding and foraging behavior. Here, we demonstrate that mice lacking the p75 neurotrophin receptor, p75NTR, have a behavioral defect in their ability to adequately respond to energy deficit. In response to fasting, p75KO mice (1) decrease their refeeding food intake compared to controls. Furthermore, following several days of restricted feeding, they (2) are unable to develop food anticipatory behavior (FAA), a phenomenon believed to be the output of a food-entrained circadian oscillator that has yet to be anatomically defined. Strikingly, these two phenotypes are observed only during the daytime, and not at night. These defects lead to increased weight loss, but do not appear to be mediated by changes in peripheral hormones. Notably, these effects are also independent of a role of p75NTR in development, as a global, adult-inducible p75NTR knockout recapitulates the feeding behavior of germline knockout mice. Rather, we demonstrate that p75NTR is discretely expressed in two hypothalamic regions known to be important for feeding behavior, the arcuate (ARC) and dorsomedial (DMH) hypothalamus. We find that p75KO mice have reduced fasting-induced activation of ARC, but not DMH, neurons. In addition, we show that ARC AgRP neuron p75NTR is necessary for fasting-induced refeeding and daytime FAA. We further suggest that AgRP-p75NTR is necessary to mediate AgRP neuron phospho-CREB signaling in response to energy deficit. Finally, given previous reports of involvement of the DMH in food anticipation, we asked whether DMH-p75NTR is necessary for feeding behavior and food anticipation. Strikingly, we find that p75NTR in the DMH is also necessary for FAA, but not for the control of homeostatic feeding. These data establish p75NTR as a novel regulator of energy homeostasis that acts to gate behavioral responses to food scarcity. It further posits that p75NTR may functionally link two independent hypothalamic regions to a time-of-day dependence of circadian food anticipation.

scholarly journals The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Brandon Podyma ◽  
Dove-Anna Johnson ◽  
Laura Sipe ◽  
Thomas Parks Remcho ◽  
Katherine Battin ◽  
...  
Keyword(s):  
Behavioral Response ◽  
Energy Homeostasis ◽  
Activity Patterns ◽  
Time Of Day ◽  
Neurotrophin Receptor ◽  
Environmental Cues ◽  
P75 Neurotrophin Receptor ◽  
Restricted Feeding ◽  
Food Scarcity ◽  
Anticipatory Behavior

Networks of neurons control feeding and activity patterns by integrating internal metabolic signals of energy balance with external environmental cues such as time-of-day. Proper circadian alignment of feeding behavior is necessary to prevent metabolic disease, and thus it is imperative that molecular players that maintain neuronal coordination of energy homeostasis are identified. Here, we demonstrate that mice lacking the p75 neurotrophin receptor, p75NTR, decrease their feeding and food anticipatory behavior (FAA) in response to daytime, but not nighttime, restricted feeding. These effects lead to increased weight loss, but do not require p75NTR during development. Instead, p75NTR is required for fasting-induced activation of neurons within the arcuate hypothalamus. Indeed, p75NTR specifically in AgRP neurons is required for FAA in response to daytime restricted feeding. These findings establish p75NTR as a novel regulator gating behavioral response to food scarcity and time-of-day dependence of circadian food anticipation.

scholarly journals Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

2008 ◽  
Vol 295 (6) ◽  
pp. F1778-F1789 ◽  
Author(s):  
Mary Beth Klinger ◽  
Margaret A. Vizzard
Keyword(s):  
Urinary Bladder ◽  
Intravesical Instillation ◽  
Bladder Function ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Female Rat ◽  
Rat Urinary Bladder ◽  
Micturition Reflex ◽  
Reflex Pathways

Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75NTR), in micturition reflex pathways after cyclophosphamide (CYP)-induced cystitis. p75NTR can bind nerve growth factor (NGF) and modulate NGF-TrkA binding and signaling. We examined p75NTR expression and the role of p75NTR in the micturition reflex in control and CYP-treated rats. p75NTR Immunoreactivity was present throughout the urinary bladder. CYP-induced cystitis (4 h, 48 h, chronic) increased ( P ≤ 0.05) p75NTR expression in whole urinary bladder as shown by Western blotting. The role of p75NTR in bladder function in control and CYP-treated rats was determined using conscious cystometry and immunoneutralization or PD90780, a compound known to specifically block NGF binding to p75NTR. An anti-p75NTR monoclonal antibody or PD90780 was infused intravesically and cystometric parameters were evaluated. Both methods of p75NTR blockade significantly ( P ≤ 0.05) decreased the intercontraction interval and void volume in control and CYP-treated rats. Intravesical infusion of PD90780 also significantly ( P ≤ 0.001) increased intravesical pressure and increased the number of nonvoiding contractions during the filling phase. Control intravesical infusions of isotype-matched IgG and vehicle were without effect. Intravesical instillation of PD90780 significantly ( P ≤ 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75NTR expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75NTR blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75NTR and NGF-TrkA signaling.

NG2-Glia, a New Player in Energy Balance

2018 ◽  
Vol 107 (3) ◽  
pp. 305-312 ◽  
Author(s):  
Sarah C. Robins ◽  
Maia V. Kokoeva
Keyword(s):  
Radiation Therapy ◽  
Energy Balance ◽  
Progenitor Cells ◽  
Clinical Implication ◽  
Energy Homeostasis ◽  
Neural Circuits ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Physiological Outcomes

There is increasing evidence that glia act not only as neuronal support cells, but that they can also influence physiological outcomes via effects on neural signalling. The role of NG2-glia in this regard is especially enigmatic, as they are known to interact with neural circuits but their precise functions other than as oligodendrocyte progenitor cells remain elusive. Here, we summarise recent evidence suggesting that NG2-glia play a role in the maintenance of energy homeostasis, most notably via the support of leptin-sensing neural circuits. We also discuss the potential clinical implication of these findings specifically in the context of cranial radiation therapy.

scholarly journals Role of Neurotrophins in the Development and Function of Neural Circuits That Regulate Energy Homeostasis

2012 ◽  
Vol 48 (3) ◽  
pp. 654-659 ◽  
Author(s):  
Samira Fargali ◽  
Masato Sadahiro ◽  
Cheng Jiang ◽  
Amy L. Frick ◽  
Tricia Indall ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Neural Circuits ◽  
And Function

scholarly journals Effect of the p75 Neurotrophin Receptor on Glycemic Control of Obese Mice during Time-Restricted Feeding

2020 ◽  
Author(s):  
Brandon Podyma ◽  
Katherine Battin ◽  
Dove-Anna Johnson ◽  
Ali D. Güler ◽  
Christopher D. Deppmann
Keyword(s):  
Glycemic Control ◽  
Glucose Homeostasis ◽  
Energy Homeostasis ◽  
Dietary Intervention ◽  
Serum Glucose ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Restricted Feeding ◽  
Obese Mice ◽  
Glucose Levels

ABSTRACTCirculating glucose regulates organismal energy homeostasis and is tightly controlled in response to feeding behavior. In overweight individuals, glucose homeostasis is often perturbed due to resistance to normal satiety signals, such as insulin and leptin, leading to type 2 diabetes and its attendant complications. An emerging dietary intervention, time-restricted feeding (TRF), aims to ameliorate the adverse metabolic consequences of obesity, however, its effectiveness on glucose control is uncertain. Here, we demonstrate that TRF is only transiently effective in reducing pre-meal serum glucose levels in obese mice lacking leptin. However, in Ob/Ob mice that also lack a gene known to suppress behavior associated with TRF, the p75 neurotrophin receptor (p75NTR), a sustained reduction of glucose levels is observed. These results suggest that the effectiveness of TRF on glycemic control can be enhanced with concurrent targeting of modulators of glucose homeostasis and TRF response.

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