Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the &#963;<sub>1</sub> receptor.

Maurice, Tangui; Strehaiano, Manon; Duhr, Fanny; Chevallier, Nathalie

Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ₁ receptor.

Maurice, Tangui; Strehaiano, Manon; Duhr, Fanny; Chevallier, Nathalie.

Afiliación

Maurice T; MMDN, Univ. Montpellier, EPHE, INSERM, UMR-S1198, Montpellier, F-34095, France. Electronic address: tangui.maurice@umontpellier.fr.
Strehaiano M; MMDN, Univ. Montpellier, EPHE, INSERM, UMR-S1198, Montpellier, F-34095, France.
Duhr F; MMDN, Univ. Montpellier, EPHE, INSERM, UMR-S1198, Montpellier, F-34095, France.
Chevallier N; MMDN, Univ. Montpellier, EPHE, INSERM, UMR-S1198, Montpellier, F-34095, France.

Behav Brain Res ; 339: 1-10, 2018 Feb 26.

Article en En | MEDLINE | ID: mdl-29129596

RESUMEN

The sigma-1 receptor (S1R) is a molecular chaperone which activity modulates several intracellular signals including calcium mobilization at mitochondria-associated endoplasmic reticulum membranes. S1R agonists are potent neuroprotectants against neurodegenerative insults and particularly in rodent models of Alzheimer's disease (AD). We here analyzed whether S1R inactivation modifies vulnerability to amyloid toxicity in AD models. Two strategies were used: (1) amyloid ß[25-35] (Aß25-35) peptide (1, 3, 9nmol) was injected intracerebroventricularly in mice treated repeatedly with the S1R antagonist NE-100 or in S1RKO mice, and (2) WT, APPSweInd, S1RKO, and APPSweInd/S1RKO mice were created and female littermates analyzed at 8 months of age. Learning deficits, oxidative stress, Bax level and BDNF content in the hippocampus were analyzed. Aß25-35 induced learning impairment, oxidative stress, Bax induction and BDNF alteration at lower dose in NE-100-treated mice or S1RKO mice as compared to WT animals. The extent of learning deficits and biochemical alterations were also higher in APPSweInd/S1RKO mice as compared to WT, APPSweInd, and S1RKO animals. S1R inactivation or altered S1R expression augmented the pathological status in pharmacologic and genetic AD mouse models. These observations, in relation with the well-known protective effects of S1R agonists, are coherent with a role of signal amplifier in neurodegeneration and neuroprotection proposed for S1R in AD and related neurodegenerative disorders.

Asunto(s)

Enfermedad de Alzheimer/genética; Péptidos beta-Amiloides/farmacología; Hipocampo/metabolismo; Fármacos Neuroprotectores/farmacología; Fragmentos de Péptidos/farmacología; Receptores sigma/metabolismo; Enfermedad de Alzheimer/metabolismo; Péptidos beta-Amiloides/metabolismo; Animales; Modelos Animales de Enfermedad; Hipocampo/efectos de los fármacos; Masculino; Trastornos de la Memoria/inducido químicamente; Trastornos de la Memoria/genética; Ratones Endogámicos C57BL; Fragmentos de Péptidos/metabolismo; Receptores sigma/efectos de los fármacos; Receptores sigma/genética; Receptor Sigma-1

Palabras clave

Alzheimer's disease; Amyloid toxicity; Knockout mice; Learning and memory; Sigma-1 receptor

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Péptidos beta-Amiloides / Receptores sigma / Fármacos Neuroprotectores / Enfermedad de Alzheimer / Hipocampo Límite: Animals Idioma: En Revista: Behav Brain Res Año: 2018 Tipo del documento: Article Pais de publicación: Países Bajos

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