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Brain Res Bull ; 181: 77-86, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35093468

RESUMEN

Hormone therapy (HT) has failed to improve learning and memory in postmenopausal women according to recent clinical studies; however, the reason for failure of HT in improving cognitive performance is unknown. In our research, we found cognitive flexibility was improved by 17ß-Estradiol (E2) in mice 1 week after ovariectomy (OVXST), but not in mice 3 months after ovariectomy (OVXLT). Isobaric tags for relative and absolute quantitation (iTRAQ) revealed increased cannabinoid receptor interacting protein 1 (CNRIP1) in E2-treated OVXLT mice compared with E2-treated OVXST mice. Adeno-associated virus 2/9 (AAV2/9) delivery of Cnrip1 short-hairpin small interfering RNA (Cnrip1-shRNA) rescued the impaired cognitive flexibility in E2 treated OVXLT mice. This effect is dependent on CB1 function, which could be blocked by AM251-a CB1 antagonist. Our results indicated a new method to increasing cognitive flexibility in women receiving HT by disrupting CNRIP1.


Asunto(s)
Antagonistas de Receptores de Cannabinoides/farmacología , Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Estradiol/farmacología , Terapia de Reemplazo de Hormonas , Corteza Prefrontal/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Femenino , Ratones , Ovariectomía , Piperidinas/farmacología , Posmenopausia , Pirazoles/farmacología , ARN Interferente Pequeño , Receptor Cannabinoide CB1/antagonistas & inhibidores
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