Adiponectin rescues synaptic plasticity in the dentate gyrus of a mouse model of Fragile X Syndrome.
Philos Trans R Soc Lond B Biol Sci
; 379(1906): 20230221, 2024 Jul 29.
Article
en En
| MEDLINE
| ID: mdl-38853554
ABSTRACT
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is the leading known single-gene cause of autism spectrum disorder. Patients with FXS display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently, there is no cure for this condition; however, there is an emerging focus on therapies that inhibit mechanistic target of rapamycin (mTOR)-dependent protein synthesis owing to the clinical effectiveness of metformin for alleviating some behavioural symptoms in FXS. Adiponectin (APN) is a neurohormone that is released by adipocytes and provides an alternative means to inhibit mTOR activation in the brain. In these studies, we show that Fmr1 knockout mice, like patients with FXS, show reduced levels of circulating APN and that both long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG) are impaired. Brief (20 min) incubation of hippocampal slices in APN (50 nM) was able to rescue both LTP and LTD in the DG and increased both the surface expression and phosphorylation of GluA1 receptors. These results provide evidence for reduced APN levels in FXS playing a role in decreasing bidirectional synaptic plasticity and show that therapies which enhance APN levels may have therapeutic potential for this and related conditions.This article is part of a discussion meeting issue 'Long-term potentiation 50 years on'.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ratones Noqueados
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Giro Dentado
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Modelos Animales de Enfermedad
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Adiponectina
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil
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Síndrome del Cromosoma X Frágil
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Plasticidad Neuronal
Límite:
Animals
Idioma:
En
Revista:
Philos Trans R Soc Lond B Biol Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá