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Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ1 receptor.
Behav Brain Res. 2018 Feb 26; 339:1-10.BB

Abstract

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 β[25-35] (Aβ25-35) 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. Aβ25-35 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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

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.

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsDisease Models, AnimalHippocampusMaleMemory DisordersMice, Inbred C57BLNeuroprotective AgentsPeptide FragmentsReceptors, sigma

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29129596

Citation

Maurice, Tangui, et al. "Amyloid Toxicity Is Enhanced After Pharmacological or Genetic Invalidation of the Σ1 Receptor." Behavioural Brain Research, vol. 339, 2018, pp. 1-10.
Maurice T, Strehaiano M, Duhr F, et al. Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ1 receptor. Behav Brain Res. 2018;339:1-10.
Maurice, T., Strehaiano, M., Duhr, F., & Chevallier, N. (2018). Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ1 receptor. Behavioural Brain Research, 339, 1-10. https://doi.org/10.1016/j.bbr.2017.11.010
Maurice T, et al. Amyloid Toxicity Is Enhanced After Pharmacological or Genetic Invalidation of the Σ1 Receptor. Behav Brain Res. 2018 Feb 26;339:1-10. PubMed PMID: 29129596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloid toxicity is enhanced after pharmacological or genetic invalidation of the σ1 receptor. AU - Maurice,Tangui, AU - Strehaiano,Manon, AU - Duhr,Fanny, AU - Chevallier,Nathalie, Y1 - 2017/11/09/ PY - 2017/09/14/received PY - 2017/11/07/accepted PY - 2017/11/14/pubmed PY - 2018/8/8/medline PY - 2017/11/14/entrez KW - Alzheimer's disease KW - Amyloid toxicity KW - Knockout mice KW - Learning and memory KW - Sigma-1 receptor SP - 1 EP - 10 JF - Behavioural brain research JO - Behav Brain Res VL - 339 N2 - 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 β[25-35] (Aβ25-35) 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. Aβ25-35 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/29129596/Amyloid_toxicity_is_enhanced_after_pharmacological_or_genetic_invalidation_of_the_σ1_receptor_ DB - PRIME DP - Unbound Medicine ER -