Factors responsible for neurofibrillary tangles and neuronal cell losses in tauopathy

Wakasaya, Yasuhito; Kawarabayashi, Tatsuhiko; Watanabe, Mitsunori; Yamamoto-Watanabe, Yukiko; Takamura, Ayumi; Kurata, Tomoko; Murakami, Tetsuro; Abe, Kōji; Yamada, Kiyofumi; Wakabayashi, Keiji; Sasaki, Atsushi; Westaway, David; George-Hyslop, Peter St; Matsubara, Etsuro; Shoji, Mikio

doi:10.1002/jnr.22572

Cited by 17 publications

(15 citation statements)

References 59 publications

(60 reference statements)

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“…The transgenic (TgTau P301L ) mice expressing the P301L mutation within the longest form of tau (2N, 4R) have previously been shown to exhibit tau pathology development in the hippocampus, amygdala, and cerebral cortex by 3 months of age, tau‐positive pretangles by 10 months of age, and extensive NFTs throughout the frontotemporal cortex at 18–24 months of age (Murakami et al., ). This progressive neuronal impairment and accumulation of NFT are associated with age‐related cognitive deficits, recapitulating the pathology seen in patients with FTD and AD (Murakami et al., ; Wakasaya et al., ).…”

Section: Introductionmentioning

confidence: 72%

Longitudinal evaluation of Tau‐P301L transgenic mice reveals no cognitive impairments at 17 months of age

et al. 2017

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IntroductionTau is a microtubule‐associated binding protein implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD). These diseases result in the intracellular accumulation of hyperphosphorylated tau in the form of neurofibrillary tangles, the presence of which is associated with cognitive deficits.MethodsWe conducted a longitudinal behavioral study to provide a profile of the TgTau(P301L)23027 transgenic mouse in multiple cognitive domains across multiple ages. P301L is the tau mutation most frequently observed in patients with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP‐17) and this mouse model recapitulates the progressive development of glial and neurofibrillary tangles, and associated cerebral atrophy observed in patients. We examined frontal cortex‐dependent executive function and attention with the touchscreen 5‐choice serial reaction time test (5‐CSRTT) and assessed the function of temporal cortical structures using novel object recognition (OR).ResultsDespite using sensitive tasks, there were no apparent changes in executive function, attention, or recognition memory in the transgenic mice from 5 to 17 months of age.ConclusionsThis study represents the first comprehensive longitudinal analysis of cognition in the TgTauP301L mouse model and suggests that this model is not ideal for studying early attention and recognition memory impairments associated with tauopathy. However, spatial and object recognition memory impairments were observed during follow‐up assessments when the mice were 18 and 21 months, respectively. These impairments are consistent with previous publications, and with a dementia‐like phenotype in these mice when aged.

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Section: Introductionmentioning

confidence: 72%

Longitudinal evaluation of Tau‐P301L transgenic mice reveals no cognitive impairments at 17 months of age

et al. 2017

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“…Fantozzi et al (2006) suggested that bone morphogenetic protein-2 may suppress the expression of AKR6A3. AKR6A3 and AKR6A5 have been associated with epilepsy and impairment of learning and memory (Busolin et al, 2011; Wakasaya et al, 2011). Deletion of AKR6A5 is often detected in patients who have monosomy 1p36 deletion syndrome, which is characterized by learning disabilities (Perkowski and Murphy, 2011).…”

Section: The Regulation Of Akrsmentioning

confidence: 99%

Regulation of Aldo–Keto Reductases in Human Diseases

Chen¹,

Zhang²

2012

Front. Pharmacol.

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The aldo–keto reductases (AKRs) are a superfamily of NAD(P)H-linked oxidoreductases, which reduce aldehydes and ketones to their respective primary and secondary alcohols. AKR enzymes are increasingly being recognized to play an important role in the transformation and detoxification of aldehydes and ketones generated during drug detoxification and xenobiotic metabolism. Many transcription factors have been identified to regulate the expression of human AKR genes, which could have profound effects on the metabolism of endogenous mediators and detoxication of chemical carcinogens. This review summarizes the current knowledge on AKR regulation by transcription factors and other mediators in human diseases.

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“…As NPAS4 is significant in inhibitory post-synaptic development and stress-induced hippocampal damage (10), the changes in NPAS4 expression were investigated and the cognitive impairment was demonstrated by behavioral changes in the rat PSD model. The results of the present study may provide laboratory references for specific biological change indicators of PSD and increase the understanding of the pathogenesis of PSD and cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of neuronal Per-Arnt-Sim domain protein 4 gene in the hippocampus of a post-stroke depression rat model

Zhao-hui

Pengge

et al. 2014

Experimental and Therapeutic Medicine

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Neuronal Per-Arnt-Sim domain protein 4 (NPAS4) is important in regulating transcription and function in the limbic system and in brain development. Post-stroke depression (PSD) is a common complication following a stroke. Furthermore, organic damage as a result of a stroke affects the restoration of nerve function and indicates that hippocampal neural activity may be associated with PSD. A PSD rat model was established via a middle cerebral artery occlusion procedure, which was combined with isolation and chronic unexpected mild stress, and was used to investigate the expression of the NPAS4 gene in the hippocampus. The neurological deficit and behavior were evaluated and NPAS4 mRNA expression was measured by semi-quantitative reverse transcription-polymerase chain reaction; furthermore, the association with cognitive impairment was analyzed. The PSD rats displayed neuropsychopathic disorders and the NPAS4 mRNA expression levels in the hippocampus were significantly lower in the depression and PSD groups compared with the control group. Therefore, the present study identified that NPAS4 expression was decreased in the hippocampus of PSD rats.

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Factors responsible for neurofibrillary tangles and neuronal cell losses in tauopathy

Cited by 17 publications

References 59 publications

Longitudinal evaluation of Tau‐P301L transgenic mice reveals no cognitive impairments at 17 months of age

Longitudinal evaluation of Tau‐P301L transgenic mice reveals no cognitive impairments at 17 months of age

Regulation of Aldo–Keto Reductases in Human Diseases

Decreased expression of neuronal Per-Arnt-Sim domain protein 4 gene in the hippocampus of a post-stroke depression rat model

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