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Mechanisms of Disease

Neuroendocrinology, metabolism and cancer

Rosa Señarís
Group Leader | Full Professor
Rosa.senaris@usc.es
 
Lab: P2L5
Field of knowledge

The group is interested in the regulation of energy homeostasis and metabolism in health and disease. In these last years, we have focused our research especially in the pathophysiology of obesity and metabolic syndrome and in the metabolism of cancer. Recently, we demonstrated that the sensory nervous system and thermal sensors like thermoTRP ion channels play a major role in the interplay between thermoregulation and metabolism. Indeed, mice deficient in the most important cold sensor, TRPM8, display hypothermia and a defective thermoregulation. Furthermore, they also develop a phenotype of obesity and circadian dysfunctions, which reveal a clear link between thermosensation, thermoregulation and energy homeostasis. Although TRPM8 ion channels were classically described in sensory peripheral ganglia, we have demonstrated that they are also expressed in brain circuits involved in autonomic thermal homeostasis, behavioral thermoregulation, and other homeostatic functions (i.e. sleep-wake cycle, feeding, osmoregulation and drinking). Moreover, we have found TRPM8 sensory fibers innervating internal organs. These results open a new window in the metabolism and thermoregulation research areas, with relevant potential implications in the physiology of fat and other metabolic organs, in the regulation of body temperature, and in processes like obesity, cachexia, inflammation and cancer.

Research Lines

  • The function of the peripheral and central thermoreceptors in the regulation of brain functions and the main metabolic organs in health and disease.
  • Search for new agonists of TRPM8 as a therapeutic strategy in obesity and metabolic syndrome
  • Metabolism of cancer: metabolic alterations in cancer-associated-cachexia (CAC) and metabolism in glioblastoma cells.

Members

Alfonso Reimúndez Dubra
Research Associate
alfonso.reimundez@usc.es

 

Sabela Caamaño Teixeira
PhD student
Valentina González Álvarez
PhD student
Luz María Casas Abeijón
Research Specialist Technician
Juan Manuel Silva Tojo
Research Specialist Technician

Selected publications

The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature

Alfonso Reimúndez, Carlos Fernández-Peña, Purificación Ordás, Pablo Hernández-Ortego, Rosalía Gallego, Cruz Morenilla-Palao, Juan Navarro, Francisco Martín-Cora, José Luís Pardo-Vázquez, Lindsay A. Schwarz, Victor Arce, Félix Viana, Rosa Señarís

Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits.

Ordas, Purificacion; Hernandez-Ortego, Pablo; Vara, Hugo; Fernandez-Pena, Carlos; Reimundez, Alfonso; Morenilla-Palao, Cruz; Guadano-Ferraz, Ana; Gomis, Ana; Hoon, Mark; Viana, Felix; Senaris, Rosa
Deletion of the Cold Thermoreceptor TRPM8 Increases Heat Loss and Food Intake Leading to Reduced Body Temperature and Obesity in Mice
Reimundez, Alfonso; Fernandez-Pena, Carlos; Garcia, Guillermo; Fernandez, Ruben; Ordas, Purificacion; Gallego, Rosalia; Pardo-Vazquez, Jose L.; Arce, Victor; Viana, Felix; Senaris, Rosa

TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins.

Meseguer V, Alpizar YA, Luis E, Tajada S, Denlinger B, Fajardo, O, Manenschijn JA, Fernández-Peña C, Talavera A, Kichko T, Navia B, Sánchez A, Señarís RM, Reeh P, Pérez- García MT, López-López JR, Voets T, Belmonte C, Talavera K, Viana F

AMPK activation by oncogenesis is required to maintain cancer cell proliferation in astrocytic tumors.

Ríos M, Foretz M, Viollet B, Prieto A, Fraga M, Costoya JA, Señarís R

Selected Results

TRPM8 ion channel, the principal cold-molecular sensor, is required to fine-tune thermoregulation and energy homeostasis. TRPM8-deficient mice exhibit deficient thermoregulatory responses to cold, hypothermia and obesity. A and B: Core body temperature (Tc) determined by telemetry in WT and TRPM8-/- mice when exposed to different environmental temperatures (A) and during fasting at 21ºC (B). C and D: TRPM8-/- present an increase of tail heat loss in fed and fasting conditions. Infrared thermography (C). TRPM8 sensory fibers innervating tail vessels in a TRPM8 reporter mouse line (D). TRPM8-deficient mice develop obesity and hyperglycemia (E-F). TRPM8 is also expressed in the CNS (H and I). (J Neurosci. 2018 Apr 11;38(15):3643-3656 and J Comp Neurol. 2019 Apr 3. doi: 10.1002/cne.24694). Our study was chosen for the cover of the Journal​.

Projects

National project(s)

Estimulación de las rutas de NO/GMPc y AMPc en la barrera hematoencefálica: una nueva estrategia ...
REF: PID2020-119178GB-I00Duration: -
PI: Manuel Campos Toimil
AGENCIA ESTATAL DE INVESTIGACION

Contracts Agreements Services

Convenio de colaboración empresarial entre la fundación científica de la Asociación Española Contra el Cáncer, la sede provincial de la Coruña de la Asociación Española contra el Cáncer, la Universidade de Santiago de Compostela en materia de ayudas predo
REF: PRDLC21570GONZDuration: -
PI: Rosa María Señarís Rodríguez
FUNDACION CIENTIFICA DE LA ASOCIACION ESPAÑOLA CONTRA EL CANCER

Alliances

Rede de Animais Transxénicos de Galicia (RATGA)