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08.05.2024 | Research Article

Alzheimer-like behavior and synaptic dysfunction in 3 × Tg-AD mice are reversed with calcineurin inhibition

verfasst von: Juan Zeng, Xian-Feng Hu, Dong-Sheng Sun, Xiao-Yue Hong, Jun-Zheng Ma, Qiong Feng

Erschienen in: Experimental Brain Research | Ausgabe 6/2024

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Abstract

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Current treatments are unable to achieve satisfactory therapeutic effects or reverse the progression of the disease. Calcineurin has been implicated as part of a critical signaling pathway for learning and memory, and neuronal calcineurin may be hyperactivated in AD. To investigate the effects and underlying mechanisms of FK506, a calcineurin inhibitor, on Alzheimer-like behavior and synaptic dysfunction in the 3 × Tg-AD transgenic mouse model of Alzheimer’s disease, we investigated the effect of FK506 on cognitive function and synaptic plasticity in the 3 × Tg-AD transgenic mouse model of Alzheimer’s disease. The results showed that FK506 treatment ameliorated cognitive deficits, as indicated by the decreased latency in the water maze, and attenuated tau hyperphosphorylation in 3 × Tg-AD mice. Treatment with FK506 also reduced the levels of certain markers of postsynaptic deficits, including PSD-95 and NR2B, and reversed the long-term potentiation deficiency and dendritic spine impairments in 3 × Tg-AD mice. These findings suggest that treatment with calcineurin inhibitors such as FK506 can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial Alzheimer’s disease and related tauopathies.

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Titel: Alzheimer-like behavior and synaptic dysfunction in 3 × Tg-AD mice are reversed with calcineurin inhibition
verfasst von: Juan Zeng
Xian-Feng Hu
Dong-Sheng Sun
Xiao-Yue Hong
Jun-Zheng Ma
Qiong Feng
Publikationsdatum: 08.05.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Experimental Brain Research / Ausgabe 6/2024
Print ISSN: 0014-4819
Elektronische ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-024-06841-8

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