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Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer´s Disease mouse model.
Armijo-Weingart, Lorena; San Martin, Loreto; Gallegos, Scarlet; Araya, Anibal; Konar-Nie, Macarena; Fernandez-Pérez, Eduardo; Aguayo, Luis G.
Afiliación
  • Armijo-Weingart L; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile; Programa de Neurociencia, Psiquiatría y Salud Mental (NEPSAM), Universidad de Concepción, Chile.
  • San Martin L; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile; Programa de Neurociencia, Psiquiatría y Salud Mental (NEPSAM), Universidad de Concepción, Chile.
  • Gallegos S; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile.
  • Araya A; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile.
  • Konar-Nie M; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile.
  • Fernandez-Pérez E; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile; Programa de Neurociencia, Psiquiatría y Salud Mental (NEPSAM), Universidad de Concepción, Chile.
  • Aguayo LG; Laboratory of Neurophysiology, Department of Physiology, Universidad de Concepción, Chile. Electronic address: laguayo@udec.cl.
Prog Neurobiol ; 237: 102616, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38723884
ABSTRACT
Alterations in cognitive and non-cognitive cerebral functions characterize Alzheimer's disease (AD). Cortical and hippocampal impairments related to extracellular accumulation of Aß in AD animal models have been extensively investigated. However, recent reports have also implicated intracellular Aß in limbic regions, such as the nucleus accumbens (nAc). Accumbal neurons express high levels of inhibitory glycine receptors (GlyRs) that are allosterically modulated by ethanol and have a role in controlling its intake. In the present study, we investigated how GlyRs in the 2xTg mice (AD model) affect nAc functions and ethanol intake behavior. Using transgenic and control aged-matched litter mates, we found that the GlyRα2 subunit was significantly decreased in AD mice (6-month-old). We also examined intracellular calcium dynamics using the fluorescent calcium protein reporter GCaMP in slice photometry. We also found that the calcium signal mediated by GlyRs, but not GABAAR, was also reduced in AD neurons. Additionally, ethanol potentiation was significantly decreased in accumbal neurons in the AD mice. Finally, we performed drinking in the dark (DID) experiments and found that 2xTg mice consumed less ethanol on the last day of DID, in agreement with a lower blood ethanol concentration. 2xTg mice also showed lower sucrose consumption, indicating that overall food reward was altered. In conclusion, the data support the role of GlyRs in nAc neuron excitability and a decreased glycinergic activity in the 2xTg mice that might lead to impairment in reward processing at an early stage of the disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Glicina / Enfermedad de Alzheimer / Núcleo Accumbens Límite: Animals Idioma: En Revista: Prog Neurobiol Año: 2024 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Glicina / Enfermedad de Alzheimer / Núcleo Accumbens Límite: Animals Idioma: En Revista: Prog Neurobiol Año: 2024 Tipo del documento: Article País de afiliación: Chile Pais de publicación: Reino Unido