Identification of an acute functional cross-talk between amyloid-β and glucocorticoid receptors at hippocampal excitatory synapses

Kootar, Scherazad; Frandemiche, Marie-Lise; Dhib, Gihen; Mouska, Xavier; Lorivel, Thomas; Poupon, Gwénola; Hunt, Hazel; Tronche, François; Bethus, Ingrid; Barik, Jacques; Marie, Hélène

doi:10.1016/j.nbd.2018.07.001

Cited by 9 publications

(7 citation statements)

References 52 publications

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“…For example, Aβ oligomers block the accumulation of CaMKIIα, a central kinase in bidirectional synaptic plasticity, at excitatory synapses during LTP induction but not at inhibitory synapses during LTD [ 74 ]. Furthermore, Kootar et al revealed by ex vivo experiments in hippocampal slices that the LTP impairment by Aß oligomers requires the functional crosstalk with glucocorticoid receptors, but the Aß oligomer-mediated LTD induction does not [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

The two faces of synaptic failure in AppNL-G-F knock-in mice

et al. 2020

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Background Intensive basic and preclinical research into Alzheimer’s disease (AD) has yielded important new findings, but they could not yet been translated into effective therapies. One of the reasons is the lack of animal models that sufficiently reproduce the complexity of human AD and the response of human brain circuits to novel treatment approaches. As a step in overcoming these limitations, new App knock-in models have been developed that avoid transgenic APP overexpression and its associated side effects. These mice are proposed to serve as valuable models to examine Aß-related pathology in “preclinical AD.” Methods Since AD as the most common form of dementia progresses into synaptic failure as a major cause of cognitive deficits, the detailed characterization of synaptic dysfunction in these new models is essential. Here, we addressed this by extracellular and whole-cell patch-clamp recordings in App NL-G-F mice compared to App NL animals which served as controls. Results We found a beginning synaptic impairment (LTP deficit) at 3–4 months in the prefrontal cortex of App NL-G-F mice that is further aggravated and extended to the hippocampus at 6–8 months. Measurements of miniature EPSCs and IPSCs point to a marked increase in excitatory and inhibitory presynaptic activity, the latter accompanied by a moderate increase in postsynaptic inhibitory function. Conclusions Our data reveal a marked impairment of primarily postsynaptic processes at the level of synaptic plasticity but the dominance of a presumably compensatory presynaptic upregulation at the level of elementary miniature synaptic function.

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Section: Discussionmentioning

confidence: 99%

The two faces of synaptic failure in AppNL-G-F knock-in mice

et al. 2020

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“…Tanto os pacientes quanto os modelos de camundongos com DA apresentam um eixo hipotálamo-hipófise adrenal desregulado, marcado por uma leve hipercortisolemia, aparente no início da patologia. Assim, no contexto da DA precoce, enquanto os níveis de proteína APP aumentam lentamente no cérebro, a atividade dos GR provavelmente está anormalmente elevada devido ao aumento nos níveis de GC 36 . Adicionalmente, o cromossomo 12p foi reconhecido como uma região associada à DA.…”

Section: Resultsunclassified

Receptores neurais e a doença de Alzheimer: uma revisão sistemática da literatura sobre as famílias de receptores mais associadas a doença, suas funções e áreas de expressão

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2019

J. bras. psiquiatr.

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RESUMO Objetivo O artigo tem como objetivo determinar as famílias de receptores mais estudadas, envolvidas com a doença de Alzheimer, assim como determinar a região do sistema nervoso na qual mais tipos de receptores são expressos e quais funções dos receptores estão predominantemente associadas com a patologia em questão. O artigo busca mostrar os modelos e métodos mais utilizados nessas pesquisas, resumindo alguns achados e discutindo o impacto desses estudos no conhecimento científico. Métodos Esta revisão utilizou-se de uma metodologia sistemática (Prospero; ID 141957). Resultados Pode-se constatar que os receptores de transcrição nuclear foram os mais estudados. A maior parte desses receptores se expressa no córtex cerebral e hipocampo. Adicionalmente, a maioria das pesquisas avaliou os receptores relacionados com os efeitos benéficos na doença. A eliminação da proteína amiloide ou o bloqueio de vias relacionadas à síntese dessa proteína foram as principais funções desempenhadas por esses receptores. Por fim, as técnicas de imunoistoquímica e reação em cadeia de polimerase em tempo real (RT-PCR), respectivamente, foram as mais utilizadas, e os roedores consistiram no principal modelo de estudo. Conclusões Os receptores de transcrição nuclear, o córtex cerebral, o hipocampo, a micróglia e a proteína beta-amiloide mostraram importância na patogênese da doença de Alzheimer neste estudo.

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“…Both AD patients and AD mice have dysregulated hypothalamic-pituitary-adrenal (HPA) axis, marked by hypercortisolemia early in the AD pathology. Thus, in early AD, while APP levels slowly increase in the brain, GR activity is probably abnormally high [37]. Moreover, GRs hyperactivation induces brain changes similar to AD changes.…”

Section: Glucocorticoid Receptorsmentioning

confidence: 98%

Alzheimer’s Disease Neuroprotection: Associated Receptors

Câmara¹

2020

Neuroprotection - New Approaches and Prospects

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Research with humans and animals has been developed over the past few years to identify receptors involved in Alzheimer's disease, aiming at a better understanding of the mechanisms and pathophysiological aspects associated with the disease. Such receptors, whether or not directly associated with current AD therapy, are relevant since their blockage or activation might result in improving or worsening the clinical scenario of the disease. In other words, such receptors might be involved in the AD prognosis. This chapter discusses some relevant points about the receptors involved with AD.

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Identification of an acute functional cross-talk between amyloid-β and glucocorticoid receptors at hippocampal excitatory synapses

Cited by 9 publications

References 52 publications

The two faces of synaptic failure in AppNL-G-F knock-in mice

The two faces of synaptic failure in AppNL-G-F knock-in mice

Receptores neurais e a doença de Alzheimer: uma revisão sistemática da literatura sobre as famílias de receptores mais associadas a doença, suas funções e áreas de expressão

Alzheimer’s Disease Neuroprotection: Associated Receptors

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