Intraneuronal accumulation of C99 contributes to synaptic alterations, apathy-like behavior, and spatial learning deficits in 3×TgAD and 2×TgAD mice. | LitMetric
Université Côte d'Azur, INSERM, CNRS, IPMC, UMR7275, Team labeled « Laboratory of Excellence (Labex) DISTALZ», Sophia-Antipolis, Valbonne, France. Electronic address:
Published: November 2018
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Article Abstract
The triple transgenic mouse model (3×TgAD: APPswe, Tau, PS1) recapitulates both amyloid β (Aβ)- and tau-related lesions as well as synaptic and memory deficits. In these mice, we reported an early apathy-like behavior and alterations in synaptic plasticity appearing concomitantly with intraneuronal accumulation of C99 in the subiculum. To delineate the genuine contribution of C99 on the above phenotypes, we generated double transgenic mice (2×TgAD: APPswe, Tau) that accumulate C99 without Aβ deposition or hyperphosphorylation of tau and compared them to 3×TgAD mice. Here, we show that both TgAD mice display similar decreases in long-term potentiation and in spontaneous locomotor activity measured by actimetry suggesting that the synaptic alterations and the apathy-like behavior were likely linked to C99 rather than Aβ. However, spatial learning alterations, assessed by the Morris water maze task, are more pronounced in 3×TgAD than in 2×TgAD, suggesting that both Aβ and C99 contribute to defects in the acquisition of spatial information. Finally, even if similar results are observed in males, cognitive and non-cognitive deficits are more severe in females.
Laboratory of Kampo Clinical Research, Oriental Medicine Research Center, School of Pharmacy, Kitasato University, Tokyo, Japan; Department of Pharmacognosy, School of Pharmacy, Kitasato University, Tokyo, Japan.
Infectious diseases are often concomitant with symptoms of lassitude and emotional disturbances, including depression, the so-called sickness behavior. Kososan, a Kampo (traditional Japanese herbal) formula, has been clinically used for depressive mood, with demonstrated efficacy in stress-induced depressive-like behavior mouse models. Additionally, our previous study has shown that nobiletin-rich kososan (NKS) prevents aging-related depressive-like behaviors and neuroinflammation in mice.
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