Adiposity signals and food reward: expanding the CNS roles of insulin and leptin

2003 ◽  
Vol 284 (4) ◽  
pp. R882-R892 ◽  
Author(s):  
Dianne P. Figlewicz
Keyword(s):  
Energy Balance ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Mental Illnesses ◽  
Therapeutic Approaches ◽  
Reward Circuitry ◽  
Feedback Model ◽  
Adiposity Signals ◽  
The Central Nervous System ◽  
The Brain

The hormones insulin and leptin have been proposed to act in the central nervous system (CNS) as adiposity signals as part of a theoretical negative feedback loop that senses the caloric stores of an animal and orchestrates adjustments in energy balance and food intake. Much research has provided support for both the existence of such a feedback loop and the specific roles that insulin and leptin may play. Most studies have focused on hypothalamic sites, which historically are implicated in the regulation of energy balance, and on the brain stem, which is a target for neural and humoral signals relating to ingestive acts. More recent lines of research, including studies from our lab, suggest that in addition to these CNS sites, brain reward circuitry may be a target for insulin and leptin action. These studies are reviewed together here with the goals of providing a historical overview of the findings that have substantiated the originally hypothesized negative feedback model and of opening up new lines of investigation that will build on these findings and allow further refinement of the model of adiposity signal/CNS feedback loop. The understanding of how motivational circuitry and its endocrine or neuroendocrine modulation contributes to normal energy balance regulation should expand possibilities for future therapeutic approaches to obesity and may lead to important insights into mental illnesses such as substance abuse or eating disorders.

scholarly journals Slow oscillations in blood pressure via a nonlinear feedback model

2001 ◽  
Vol 280 (4) ◽  
pp. R1105-R1115 ◽  
Author(s):  
John V. Ringwood ◽  
Simon C. Malpas
Keyword(s):  
Blood Pressure ◽  
Feedback Loop ◽  
Sympathetic Nerve Activity ◽  
Linear Feedback ◽  
Scaling Effects ◽  
Nonlinear Feedback ◽  
Nerve Activity ◽  
Feedback Model ◽  
The Central Nervous System ◽  
Proportional Derivative Controller

Blood pressure is well established to contain a potential oscillation between 0.1 and 0.4 Hz, which is proposed to reflect resonant feedback in the baroreflex loop. A linear feedback model, comprising delay and lag terms for the vasculature, and a linear proportional derivative controller have been proposed to account for the 0.4-Hz oscillation in blood pressure in rats. However, although this model can produce oscillations at the required frequency, some strict relationships between the controller and vasculature parameters must be true for the oscillations to be stable. We developed a nonlinear model, containing an amplitude-limiting nonlinearity that allows for similar oscillations under a very mild set of assumptions. Models constructed from arterial pressure and sympathetic nerve activity recordings obtained from conscious rabbits under resting conditions suggest that the nonlinearity in the feedback loop is not contained within the vasculature, but rather is confined to the central nervous system. The advantage of the model is that it provides for sustained stable oscillations under a wide variety of situations even where gain at various points along the feedback loop may be altered, a situation that is not possible with a linear feedback model. Our model shows how variations in some of the nonlinearity characteristics can account for growth or decay in the oscillations and situations where the oscillations can disappear altogether. Such variations are shown to accord well with observed experimental data. Additionally, using a nonlinear feedback model, it is straightforward to show that the variation in frequency of the oscillations in blood pressure in rats (0.4 Hz), rabbits (0.3 Hz), and humans (0.1 Hz) is primarily due to scaling effects of conduction times between species.

scholarly journals DOPA Homeostasis by Dopamine: A Control-Theoretic View

2021 ◽  
Vol 22 (23) ◽  
pp. 12862
Author(s):  
Rune Kleppe ◽  
Qaiser Waheed ◽  
Peter Ruoff
Keyword(s):  
Oxidative Stress ◽  
Experimental Data ◽  
Negative Feedback ◽  
Neural Activity ◽  
Feedback Loop ◽  
Feedback Inhibition ◽  
Zero Order ◽  
Negative Feedback Loop ◽  
Zero Order Kinetics ◽  
The Brain

Dopamine (DA) is an important signal mediator in the brain as well as in the periphery. The term “dopamine homeostasis” occasionally found in the literature refers to the fact that abnormal DA levels can be associated with a variety of neuropsychiatric disorders. An analysis of the negative feedback inhibition of tyrosine hydroxylase (TH) by DA indicates, with support from the experimental data, that the TH-DA negative feedback loop has developed to exhibit 3,4-dihydroxyphenylalanine (DOPA) homeostasis by using DA as a derepression regulator. DA levels generally decline when DOPA is removed, for example, by increased oxidative stress. Robust DOPA regulation by DA further implies that maximum vesicular DA levels are established, which appear necessary for a reliable translation of neural activity into a corresponding chemical transmitter signal. An uncontrolled continuous rise (windup) in DA occurs when Levodopa treatment exceeds a critical dose. Increased oxidative stress leads to the successive breakdown of DOPA homeostasis and to a corresponding reduction in DA levels. To keep DOPA regulation robust, the vesicular DA loading requires close to zero-order kinetics combined with a sufficiently high compensatory flux provided by TH. The protection of DOPA and DA due to a channeling complex is discussed.

scholarly journals Flies, clocks and evolution

2001 ◽  
Vol 356 (1415) ◽  
pp. 1769-1778 ◽  
Author(s):  
Ezio Rosato ◽  
Charalambos P. Kyriacou
Keyword(s):  
Gene Regulation ◽  
Negative Feedback ◽  
Clock Gene ◽  
Circadian System ◽  
Gene Duplications ◽  
Closely Related Species ◽  
Feedback Model ◽  
Silk Moth ◽  
The Brain

The negative feedback model for gene regulation of the circadian mechanism is described for the fruitfly, Drosophila melanogaster . The conservation of function of clock molecules is illustrated by comparison with the mammalian circadian system, and the apparent swapping of roles between various canonical clock gene components is highlighted. The role of clock gene duplications and divergence of function is introduced via the timeless gene. The impressive similarities in clock gene regulation between flies and mammals could suggest that variation between more closely related species within insects might be minimal. However, this is not borne out because the expression of clock molecules in the brain of the giant silk moth, Antheraea pernyi , is not easy to reconcile with the negative feedback roles of the period and timeless genes. Variation in clock gene sequences between and within fly species is examined and the role of co-evolution between and within clock molecules is described, particularly with reference to adaptive functions of the circadian phenotype.

scholarly journals Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Almudena Fuster-Matanzo ◽  
María Llorens-Martín ◽  
Félix Hernández ◽  
Jesús Avila
Keyword(s):  
Immune Response ◽  
Alzheimer Disease ◽  
Adult Neurogenesis ◽  
The Elderly ◽  
Therapeutic Approaches ◽  
Common Cause ◽  
The Central Nervous System ◽  
Chronic Activation ◽  
The Brain

Neuroinflammation, a specialized immune response that takes place in the central nervous system, has been linked to neurodegenerative diseases, and specially, it has been considered as a hallmark of Alzheimer disease, the most common cause of dementia in the elderly nowadays. Furthermore, neuroinflammation has been demonstrated to affect important processes in the brain, such as the formation of new neurons, commonly known as adult neurogenesis. For this, many therapeutic approaches have been developed in order to avoid or mitigate the deleterious effects caused by the chronic activation of the immune response. Considering this, in this paper we revise the relationships between neuroinflammation, Alzheimer disease, and adult neurogenesis, as well as the current therapeutic approaches that have been developed in the field.

P4-220: Identification of a negative feedback loop in the brain for the regulation of neurosteroid synthesis: Implications for Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T735-T736
Author(s):  
Sivan Vadakkadath Meethal ◽  
Hsien Chan ◽  
Erika Ginsburg ◽  
Andrea C. Wilson ◽  
Richard L. Bowen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
The Brain

scholarly journals Hypothalamic pathways linking energy balance and reproduction

2008 ◽  
Vol 294 (5) ◽  
pp. E827-E832 ◽  
Author(s):  
Jennifer W. Hill ◽  
Joel K. Elmquist ◽  
Carol F. Elias
Keyword(s):  
Energy Balance ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Arcuate Nucleus ◽  
Metabolic Stress ◽  
Reproductive Function ◽  
Reproductive Axis ◽  
Hypothalamic Nuclei ◽  
Adiposity Signals ◽  
The Brain

During periods of metabolic stress, animals must channel energy toward survival and away from processes such as reproduction. The reproductive axis, therefore, has the capacity to respond to changing levels of metabolic cues. The cellular and molecular mechanisms that link energy balance and reproduction, as well as the brain sites mediating this function, are still not well understood. This review focuses on the best characterized of the adiposity signals: leptin and insulin. We examine their reproductive role acting on the classic metabolic pathways of the arcuate nucleus, NPY/AgRP and POMC/CART neurons, and the newly identified kisspeptin network. In addition, other hypothalamic nuclei that may play a role in linking metabolic state and reproductive function are discussed. The nature of the interplay between these elements of the metabolic and reproductive systems presents a fascinating puzzle, whose pieces are just beginning to fall into place.

Mesocestoides corti intracranial infection as a murine model for neurocysticercosis

Parasitology ◽  
2010 ◽  
Vol 137 (3) ◽  
pp. 359-372 ◽  
Author(s):  
JORGE I. ALVAREZ ◽  
BIBHUTI B. MISHRA ◽  
UMA MAHESH GUNDRA ◽  
PRAMOD K. MISHRA ◽  
JUDY M. TEALE
Keyword(s):  
Immune Responses ◽  
Murine Model ◽  
Taenia Solium ◽  
Toll Like Receptor ◽  
Therapeutic Approaches ◽  
Larval Form ◽  
The Central Nervous System ◽  
Receptor Signaling Pathway ◽  
Kinetics Of ◽  
The Brain

SUMMARYNeurocysticercosis (NCC) is the most common parasitic disease of the central nervous system (CNS) caused by the larval form of the tapeworm Taenia solium. NCC has a long asymptomatic period with little or no inflammation, and the sequential progression to symptomatic NCC depends upon the intense inflammation associated with degeneration of larvae. The mechanisms involved in these progressive events are difficult to study in human patients. Thus it was necessary to develop an experimental model that replicated NCC. In this review, we describe studies of a murine model of NCC in terms of the release/secretion of parasite antigens, immune responses elicited within the CNS environment and subsequent pathogenesis. In particular, the kinetics of leukocyte subsets infiltrating into the brain are discussed in the context of disruption of the CNS barriers at distinct anatomical sites and the mechanisms contributing to these processes. In addition, production of various inflammatory mediators and the mechanisms involved in their induction by the Toll-like receptor signaling pathway are described. Overall, the knowledge gained from the mouse model of NCC has provided new insights for understanding the kinetics of events contributing to different stages of NCC and should aid in the formulation of more effective therapeutic approaches.

scholarly journals The State of The Art on Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
pp. 117957352110291
Author(s):  
Immacolata Vecchio ◽  
Luca Sorrentino ◽  
Annamaria Paoletti ◽  
Rosario Marra ◽  
Mariamena Arbitrio
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
State Of The Art ◽  
Acetylcholinesterase Inhibitors ◽  
Therapeutic Approaches ◽  
Clinical Level ◽  
Novel Drugs ◽  
Clinical Benefits ◽  
The Central Nervous System ◽  
The Brain

Alzheimer’s disease (AD) is a chronic disabling disease that affects the central nervous system. The main consequences of AD include the decline of cognitive functions and language disorders. One of the causes leading to AD is the decrease of neurotransmitter acetylcholine (ACh) levels in the brain, in part due to a higher activity of acetylcholinesterase (AChE), the enzyme responsible for its degradation. Many acetylcholinesterase inhibitors (AChEIs), both natural and synthetic, have been developed and used through the years to counteract the progression of the disease. The first of such drugs approved for a therapeutic use was tacrine, that binds through a reversible bond to the enzyme. However, tacrine has since been withdrawn because of its adverse effects. Currently, donepezil and galantamine are very promising AChEIs with clinical benefits. Moreover, rivastigmine is considered a pseudo-irreversible compound with anti-AChE action, providing similar effects at the clinical level. The purpose of this review is to provide an overview of what has been published over the last decade on the effectiveness of AChEIs in AD, analysing the most relevant issues under the clinical and methodological profiles and the consequent possible welfare effects for the whole world. Furthermore, novel drugs and possible therapeutic approaches are also discussed.

scholarly journals A molecular approach to Glioblastoma Multiforme

2016 ◽  
Vol 1 (1) ◽  
pp. 35
Author(s):  
Amit Verma ◽  
Swetha Gunasekar ◽  
Vineeta Goel ◽  
Randeep Singh ◽  
Ramandeep Singh Arora ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Poor Prognosis ◽  
Molecular Profiling ◽  
Molecular Approach ◽  
Genomic Information ◽  
Therapeutic Approaches ◽  
Detailed Understanding ◽  
The Central Nervous System ◽  
The Brain ◽  
Novel Therapeutic

<p>Glioma is a tumor of the central nervous system that occurs in the glial cells, Which it surrounds and protects the nerve cells. Glioblastoma Multiforme (GBM) is the most common and malignant sub-type of gliomas that arises from star-shaped cells called “astrocytes”, which constitute the supportive tissue of the brain. GBM are known to be heterogeneous in outcome with majority having a poor prognosis, thus there is an urgent need for novel therapeutic approaches. The detailed understanding of GBM is established by the combination of histopathology and genomic information of the tumor that aids in the best choice of Personalized Medicine. In this article, seven GBM patients are discussed who underwent tissue diagnosis as well as tumor molecular profiling; the significance of the genes and associated mutations/variations picked up in each individual.</p>

scholarly journals Role of GABA-A and GABA-B receptors of the brain in the hypothalamo-pituitary-testicular regulation by the negative feedback mechanism

1995 ◽  
Vol 41 (4) ◽  
pp. 36-38
Author(s):  
Ye. V. V. Naumenko ◽  
A. V. Amikishiyeva ◽  
L. I. Serova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Negative Feedback ◽  
Feedback Mechanism ◽  
Gaba A ◽  
Negative Feedback Mechanism ◽  
The Central Nervous System ◽  
The Brain ◽  
Stimulation Of

The role of gamma-aminobutyric acid (GABA) of the brain and its receptors in the hypothalamo-pituitary-testicular (HPT) regulation by the negative feedback mechanism was for the first time studied in sham-operated and unilaterally castrated adult Wister rats. Increased level of GABA in the central nervous system following an injection of GABA transaminase inhibitor, aminoacetic acid, into the lateral ventricle of the brain was associated with activation of a compensatory increase of testosterone level in the blood, caused by unilateral castration. GABA effect is mediated through the receptors. Muscimol stimulation of GABA-A receptors of the central nervous system activated and their blocking with bicucullin inhibited a compensatory increase of testosterone level in the blood caused by hemicastration. Baclofen stimulation of cerebral GABA-B receptors was associated with an inhibition and their saclofen blocking with stimulation of the level of male sex steroid hormone in the blood following unilateral castration. A conclusion is made about participation of GABAergic mechanisms of the brain in the regulation of HPT function via the negative feedback mechanism

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