Learning strategy preference of 5XFAD transgenic mice depends on the sequence of place/spatial and cued training in the water maze task

Cho, Woo-Hyun; Park, Jung-Cheol; Chung, ChiHye; Jeon, Won Kyung; Han, Jung‐Soo

doi:10.1016/j.bbr.2014.07.033

Cited by 17 publications

(19 citation statements)

References 28 publications

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“…Specifically, cognitive status was measured in vehicle-treated non-transgenic, vehicle-treated 5XFAD, and F. mume- treated 5XFAD mice using the Morris water maze, location novelty recognition, and contextual fear conditioning tasks. Impairments in the spatial version of the Morris water maze task, location novelty recognition task, and contextual fear conditioning task were observed in vehicle-treated 5XFAD mice relative to vehicle-treated non-transgenic mice, which is consistent with earlier reports [ 20 , 38 ]. These cognitive impairments were alleviated in the F. mume -treated 5XFAD mice.…”

Section: Discussionsupporting

confidence: 92%

Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice

Park

Jeon

et al. 2015

BMC Complement Altern Med

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Background Fructus mume (F. mume) has been used as a traditional treatment for ulcer, cough, and digestive problems for many years in Asian countries. Previous studies have demonstrated that F. mume extracts alleviate cognitive deficits in rats with chronic cerebral hypoperfusion and in mice with scopolamine treatments. The present experiment was conducted to examine the effects of F. mume on cognitive impairments in 5XFAD transgenic mice with five familial Alzheimer’s disease (AD) mutations.Methods F. mume was administered daily to 5XFAD mice at 12 weeks of age and continued for 90 days. Cognitive function was evaluated using a spatial memory version of the Morris water maze task, the object/location novelty recognition test, and contextual fear conditioning at 24 weeks of age. To elucidate the possible mechanisms underlying the memory improving effects of F. mume in 5XFAD mice, we examined alterations in hippocampal cholinergic function.ResultsVehicle-treated 5XFAD mice exhibited hippocampus-dependent memory impairments compared with non-transgenic littermates, which was reversed in F. mume-treated 5XFAD mice. In addition, reduced hippocampal choline acetyltransferase (ChAT) levels in 5XFAD mice were reversed by F. mume treatment, indicating that F. mume enhances the effects of cholinergic neuronal function.Conclusions F. mume may have therapeutic effects on cognitive impairments in AD.

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Section: Discussionsupporting

confidence: 92%

Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice

Park

Jeon

et al. 2015

BMC Complement Altern Med

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“…This alteration of pCREB expression is a dynamic process and the time course of the pCREB levels might be different according to the selected brain region and the learning strategy implemented by the task. Furthermore, the learning strategy-switching task used herein might be useful in studying cognitive function impaired by abundant intraneuronal Aβ accumulation and extracellular plague deposition that occurs in the brains of a transgenic mouse model of Alzheimer’s disease (Cho et al, 2014 ), which is used to study memory deficits and for the development of preventive treatments.…”

Section: Discussionmentioning

confidence: 99%

Differences in the Flexibility of Switching Learning Strategies and CREB Phosphorylation Levels in Prefrontal Cortex, Dorsal Striatum and Hippocampus in Two Inbred Strains of Mice

Cho

Han

2016

Front. Behav. Neurosci.

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Flexibility in using different learning strategies was assessed in two different inbred strains of mice, the C57BL/6 and DBA/2 strains. Mice were trained sequentially in two different Morris water maze protocols that tested their ability to switch their learning strategy to complete a new task after first being trained in a different task. Training consisted either of visible platform trials (cued training) followed by subsequent hidden platform trials (place training) or the reverse sequence (place training followed by cued training). Both strains of mice showed equivalent performance in the type of training (cued or place) that they received first. However, C57BL/6 mice showed significantly better performances than DBA/2 mice following the switch in training protocols, irrespective of the order of training. After completion of the switched training session, levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) were measured in the hippocampus, striatum and prefrontal cortex of the mice. Prefrontal cortical and hippocampal pCREB levels differed by strain, with higher levels found in C57BL/6 mice than in DBA/2 mice. No strain differences were observed in the medial or lateral region of the dorsal striatum. These findings indicate that the engagement (i.e., CREB signaling) of relevant neural structures may vary by the specific demands of the learning strategy, and this is closely tied to differences in the flexibility of C57BL/6 and DBA/2 mice to switch their learning strategies when given a new task.

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“…Two-way repeated-measures ANOVA on the search error of the place training revealed a significant effect of the session (F (3,78) = 3.250, p < 0.05), but no significant effect of group (F (1,26) = 2.957, p = 0.097) and no significant interaction effect of group × session (F (3,78) = 1.339, p = 0.268). Procedural knowledge of the task acquired in the prior cued training has been reported to interfere with the use of the spatial strategy needed to perform the place task efficiently more in 6-month-old 5XFAD mice than non-Tg control mice [ 20 ]. Therefore, we divided place training into two sessions (the first 8 trials and second 8 trials) and analyzed the search patterns of mice using criteria mentioned earlier ( Figure 1 B) [ 19 , 20 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…Each mouse serially received a cued/response and place/spatial version of the water maze task, adopted from McDonald and White [14] and modified in our previous studies [17,[19][20][21]. Briefly, each mouse received cued/response training for 4 days, followed by place/spatial training for four days.…”

Section: Behavioral Training Proceduresmentioning

confidence: 99%

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4-Hydroxynonenal Immunoreactivity Is Increased in the Frontal Cortex of 5XFAD Transgenic Mice

et al. 2020

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Oxidative stress was implicated in the functional impairment of the frontal cortex observed in early Alzheimer’s disease (AD). To elucidate this role in an animal AD model, we assessed cognitive function of 4-month-old five familial AD (5XFAD) transgenic (Tg) mice using a learning strategy-switching task requiring recruitment of the frontal cortex and measuring levels of 4-hydroxy-2-trans-nonenal (4-HNE), a marker of oxidative stress, in their frontal cortex. Mice were sequentially trained in cued/response and place/spatial versions of the water maze task for four days each. 5XFAD and non-Tg mice exhibited equal performance in cued/response training. However, 5XFAD mice used spatial search strategy less than non-Tg mice in the spatial/place training. Immunoblot and immunofluorescence staining showed that 4-HNE levels increased in the frontal cortex, but not in the hippocampus and striatum, of 5XFAD mice compared to those in non-Tg mice. We report early cognitive deficits related to the frontal cortex and the frontal cortex’s oxidative damage in 4-month-old 5XFAD mice. These results suggest that 4-month-old 5XFAD mice be a useful animal model for the early diagnosis and management of AD.

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Learning strategy preference of 5XFAD transgenic mice depends on the sequence of place/spatial and cued training in the water maze task

Cited by 17 publications

References 28 publications

Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice

Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice

Differences in the Flexibility of Switching Learning Strategies and CREB Phosphorylation Levels in Prefrontal Cortex, Dorsal Striatum and Hippocampus in Two Inbred Strains of Mice

4-Hydroxynonenal Immunoreactivity Is Increased in the Frontal Cortex of 5XFAD Transgenic Mice

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