stable-knockdown-genes-encoding-extracellular-matrix-proteins-c2c12

Stable Knockdown of Genes Encoding Extracellular Matrix Proteins in the C2C12 Myoblast Cell Line Using Small-Hairpin (sh)RNA

Extracellular matrix (ECM) proteins are crucial for skeletal muscle development and homeostasis. The stable knockdown of genes coding for ECM proteins in ...

Icahn School of Medicine at Mount Sinai

FGF19: How gut talks to brain to keep your sugar down.

Sweet signals and diabetes: Carbohydrate-binding proteins contribute to insulin resistance.

Altered dopamine signaling in obesity might decrease physical activity without contributing to weight gain.

A weighty problem.

Reproductive hormones alter activity in neural circuits linking reward and social interactions.

Addicted to love?

The central nervous system (CNS) plays a vital role in regulating energy balance and metabolism. Over the last 50 years, studies in animal models have allowed us to identify critical CNS regions involved in these processes and even crucial cell populations. Now, techniques for genetically and anatomically targeted manipulation of specific neural populations using light (optogenetic), ligands (chemogenetic), or magnetic fields (radiogenetic/magnetogenetic) allow detailed investigation of circuits involved in metabolic regulation. In this review, we provide a brief overview of recent studies using light- and magnetic field-regulated neural activity to investigate the neural circuits contributing to metabolic control.

Investigating metabolic regulation using targeted neuromodulation.

Diabetes: Peripheral nerve modulation to treat metabolic disease.

The central nervous system relies on a continual supply of glucose, and must be able to detect glucose levels and regulate peripheral organ functions to ensure that its energy requirements are met. Specialized glucose-sensing neurons, first described half a century ago, use glucose as a signal and modulate their firing rates as glucose levels change. Glucose-excited neurons are activated by increasing glucose concentrations, while glucose-inhibited neurons increase their firing rate as glucose concentrations fall and decrease their firing rate as glucose concentrations rise. Glucose-sensing neurons are present in multiple brain regions and are highly expressed in hypothalamic regions, where they are involved in functions related to glucose homeostasis. However, the roles of glucose-sensing neurons in healthy and disease states remain poorly understood. Technologies that can rapidly and reversibly activate or inhibit defined neural populations provide invaluable tools to investigate how specific neural populations regulate metabolism and other physiological roles. Optogenetics has high temporal and spatial resolutions, requires implants for neural stimulation, and is suitable for modulating local neural populations. Chemogenetics, which requires injection of a synthetic ligand, can target both local and widespread populations. Radio- and magnetogenetics offer rapid neural activation in localized or widespread neural populations without the need for implants or injections. These tools will allow us to better understand glucose-sensing neurons and their metabolism-regulating circuits.

Remote control of glucose-sensing neurons to analyze glucose metabolism.

The ability to observe the effects of rapidly and reversibly regulating cell activity in targeted cell populations has provided numerous physiologic insights. Over the last decade, a wide range of technologies have emerged for regulating cellular activity using optical, chemical, and, more recently, electromagnetic modalities. Electromagnetic fields can freely penetrate cells and tissue and their energy can be absorbed by metal particles. When released, the absorbed energy can in turn gate endogenous or engineered receptors and ion channels to regulate cell activity. In this manner, electromagnetic fields acting on external nanoparticles have been used to exert mechanical forces on cell membranes and organelles to generate heat and interact with thermally activated proteins or to induce receptor aggregation and intracellular signaling. More recently, technologies using genetically encoded nanoparticles composed of the iron storage protein, ferritin, have been used for targeted, temporal control of cell activity in vitro and in vivo. These tools provide a means for noninvasively modulating gene expression, intracellular organelles, such as endosomes, and whole-cell activity both in vitro and in freely moving animals. The use of magnetic fields interacting with external or genetically encoded nanoparticles thus provides a rapid noninvasive means for regulating cell activity.

Electromagnetic Regulation of Cell Activity.

Glucose homeostasis requires an organism to rapidly respond to changes in plasma glucose concentrations. Iatrogenic hypoglycemia as a result of treatment with insulin or sulfonylureas is the most common cause of hypoglycemia in humans and is generally only seen in patients with diabetes who take these medications. The first response to a fall in glucose is the detection of impending hypoglycemia by hypoglycemia-detecting sensors, including glucose-sensing neurons in the hypothalamus and other regions. This detection is then linked to a series of neural and hormonal responses that serve to prevent the fall in blood glucose and restore euglycemia. In this review, we discuss the current state of knowledge about central glucose sensing and how detection of a fall in glucose leads to the stimulation of counterregulatory hormone and behavior responses. We also review how diabetes and recurrent hypoglycemia impact glucose sensing and counterregulation, leading to development of impaired awareness of hypoglycemia in diabetes.

Article	Year
FGF19: How gut talks to brain to keep your sugar down. Molecular metabolism\| PubMed ID: 24567899	2014
Sweet signals and diabetes: Carbohydrate-binding proteins contribute to insulin resistance. Science translational medicine\| PubMed ID: 27881819	2016
A weighty problem. Science translational medicine\| PubMed ID: 28077682	2017
Addicted to love? Science translational medicine\| PubMed ID: 28228599	2017
Investigating metabolic regulation using targeted neuromodulation. Annals of the New York Academy of Sciences\| PubMed ID: 29106710	2018
Diabetes: Peripheral nerve modulation to treat metabolic disease. Nature reviews. Endocrinology\| PubMed ID: 29498375	2018
Remote control of glucose-sensing neurons to analyze glucose metabolism. American journal of physiology. Endocrinology and metabolism\| PubMed ID: 29812985	2018
Electromagnetic Regulation of Cell Activity. Cold Spring Harbor perspectives in medicine\| PubMed ID: 30249601	2019
Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia. Endocrine reviews\| PubMed ID: 30689785	2019

Sarah Stanley

Biography

JoVE Journal Publications

Other Publications