Acclimatize
Financiado
Hypothalamic mechanisms of thermal homeostasis and adaptation
Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain’s neural thermostat is made up by ce...
Mammalian organisms possess the remarkable ability to maintain internal body temperature (Tcore) within a narrow range close to 37°C despite wide environmental temperature variations. The brain’s neural thermostat is made up by central circuits in the hypothalamic preoptic area (POA), which orchestrate peripheral thermoregulatory responses to maintain Tcore. Thermogenesis requires metabolic fuel, suggesting intricate connections between the thermoregulatory centre and hypothalamic circuits controlling energy balance. How the POA detects and integrates temperature and metabolic information to achieve thermal balance is largely unknown. A major question is whether this circuitry could be harnessed therapeutically to treat obesity.
We have recently identified the first known molecular temperature sensor in thermoregulatory neurons of the POA, transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive ion channel. I aim to use TRPM2 as a molecular marker to gain access to and probe the function of thermoregulatory neurons in vivo. I propose a multidisciplinary approach, combining local, in vivo POA temperature stimulation with optogenetic circuit-mapping to uncover the molecular and cellular logic of the hypothalamic thermoregulatory centre and to assess its medical potential to counteract metabolic syndrome.
Acclimation is a beneficial adaptive process that fortifies thermal responses upon environmental temperature challenges. Thermoregulatory neuron plasticity is thought to mediate acclimation. Conversely, maladaptive thermoregulatory changes affect obesity. The cell-type-specific neuronal plasticity mechanisms underlying these changes within the POA, however, are unknown.
Using ex-vivo slice electrophysiology and in vivo imaging, I propose to characterize acclimation- and obesity-induced plasticity of thermoregulatory neurons. Ultimately, I aim to manipulate thermoregulatory neuron plasticity to test its potential counter-balancing effect on obesity.
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Duración del proyecto: 84 meses
Fecha Inicio: 2018-02-22
Fecha Fin: 2025-02-28
Fecha Fin: 2025-02-28
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2018-02-22
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2017-COG:
ERC Consolidator Grant
Cerrada
hace 7 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
UNIVERSITATSKLINIKUM HEIDELBERG
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
2.68M€ |
Participante