Publications

Authors:

Pedrazzoli, Matteo; Losurdo, Morris; Paolone, Giovanna; Medelin, Manuela; Jaupaj, Lejdi; Cisterna, Barbara; Slanzi, Anna; Malatesta, Manuela; Coco, Silvia; Buffelli, Mario

Title:

Glucocorticoid receptors modulate dendritic spine plasticity and microglia activity in an animal model of Alzheimer's disease

Year:

2019

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

NEUROBIOLOGY OF DISEASE

ISSN of journal:

0969-9961

N° Volume:

132

Number or Folder:

104568

:

Academic Press Incorporated:6277 Sea Harbor Drive:Orlando, FL 32887:(800)543-9534, (407)345-4100, EMAIL: ap@acad.com, INTERNET: http://www.idealibrary.com, Fax: (407)352-3445

Page numbers:

1-11

Keyword:

Alzheimer's disease; Dendritic spines; Glucocorticoid receptor; Glucocorticoids; Hippocampus; Microglia

Short description of contents:

Chronic exposure to high circulating levels of glucocorticoids (GCs) may be a key risk factor for Alzheimer's Disease (AD) development and progression. In addition, hyper-activation of glucocorticoid receptors (GRs) induces brain alterations comparable to those produced by AD. In transgenic mouse models of AD, GCs increase the production of the most important and typical hallmarks of this dementia such as: Aβ40, Aβ42 and tau protein (both the total tau and its hyperphosphorylated isoforms). Moreover, GCs in brain are pivotal regulators of dendritic spine turnover and microglia activity, two phenomena strongly altered in AD. Although it is well-established that GCs primes the neuroinflammatory response in the brain to some stimuli, it is unknown whether or how GRs modulates dendritic spine plasticity and microglia activity in AD. In this study, we evaluated, using combined Golgi Cox and immunofluorescence techniques, the role of GR agonists and antagonists on dendritic spine plasticity and microglia activation in hippocampus of 3xTg-AD mice. We found that dexamethasone, an agonist of GRs, was able to significantly reduce dendritic spine density and induced proliferation and activation of microglia in CA1 region of hippocampus of 3xTg-AD mice at 6 and 10 months of age. On the contrary, the treatment with mifepristone, an antagonist of GRs, strongly enhanced dendritic spine density, decreased microglia density and improved the behavioural performance of 3xTg-AD mice. Additionally, primary microglial cells in vitro were directly activated by dexamethasone. Together, these data demonstrate that stress exacerbates AD and promotes a rapid progression of the pathology acting on both neurons and glial cells, supporting an important pro-inflammatory role of GC within CNS in AD. Consequently, these results further strengthen the need to test clinical interventions that correct GCs dysregulation as promising therapeutic strategy to delay the onset and slow down the progression of AD.

Web page:

https://doi.org/10.1016/j.nbd.2019.104568

Product ID:

109905

Handle IRIS:

11562/998908

Last Modified:

November 15, 2022

Bibliographic citation:

Pedrazzoli, Matteo; Losurdo, Morris; Paolone, Giovanna; Medelin, Manuela; Jaupaj, Lejdi; Cisterna, Barbara; Slanzi, Anna; Malatesta, Manuela; Coco, Silvia; Buffelli, Mario, Glucocorticoid receptors modulate dendritic spine plasticity and microglia activity in an animal model of Alzheimer's disease «NEUROBIOLOGY OF DISEASE» , vol. 132 , n. 104568 , 2019 , pp. 1-11

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