CART treatment improves memory and synaptic structure in APP/PS1 mice

Jin, Jiali; Liou, Anthony Kian-Fong; Shi, Yejie; Yin, Kang; Chen, Ling; Li, Lingling; Zhu, Xiaolei; Lai, Qi; Yang, Rong; Chen, Jun; Xu, Yun

doi:10.1038/srep10224

Cited by 37 publications

(28 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, in the present study, we also investigated the efficacy of TRF to preserve recognition memory in AβPP/PS1 mice using a spontaneous behavioral response (exploration of novel objects) that does not require stimulus presentation [47]. Our results demonstrated that the AβPP/PS1 mice supplemented daily with water showed a significant decline in novel object exploration time compared with aged-matched WT, consistent with other age-related memory impairment in AβPP/PS1 mice [48–50]. This decline in cognitive function was rescued to a greater extent by daily TRF supplementation than by PO, suggesting TRF is the active antifibrillogenic and neuroprotective component.…”

Section: Discussionsupporting

confidence: 67%

Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice

Ibrahim

Yanagisawa

Durani

et al. 2016

JAD

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common cause of dementia. The cardinal neuropathological characteristic of AD is the accumulation of amyloid-β (Aβ) into extracellular plaques that ultimately disrupt neuronal function and lead to neurodegeneration. One possible therapeutic strategy therefore is to prevent Aβ aggregation. Previous studies have suggested that vitamin E analogs slow AD progression in humans. In the present study, we investigated the effects of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm oil, on amyloid pathology in vitro and in vivo. TRF treatment dose-dependently inhibited the formation of Aβ fibrils and Aβ oligomers in vitro. Moreover, daily TRF supplementation to AβPPswe/PS1dE9 double transgenic mice for 10 months attenuated Aβ immunoreactive depositions and thioflavin-S-positive fibrillar type plaques in the brain, and eventually improved cognitive function in the novel object recognition test compared with control AβPPswe/PS1dE9 mice. The present result indicates that TRF reduced amyloid pathology and improved cognitive functions, and suggests that TRF is a potential therapeutic agent for AD.

show abstract

Section: Discussionsupporting

confidence: 67%

Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice

Ibrahim

Yanagisawa

Durani

et al. 2016

JAD

View full text Add to dashboard Cite

show abstract

“…Not only that, Cocaine-and amphetamine-regulated transcript (Exogenous CART treatment) in APP/PS1 mice has obstructed depolarization of the mitochondrial membrane and provoke mitochondrial complex, I and II activities, thereby leading to an increase in ATP levels. Further, CART treatment also reduces ROS and 4-HNE level that mitigate oxidative DNA damage in AD brain [186]. In case of PD, MicroRNA-7 (miR-7) has been found to elicit a protective role in cellular models of PD.…”

Section: Methazolamide (Mtz)mentioning

confidence: 99%

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Jha

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Mounting evidence suggests a link between metabolic syndrome (MetS) such as diabetes, obesity, non-alcoholic fatty liver disease in the progression of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases (NDDs). For instance, accumulated Aβ oligomer is enhancing neuronal Ca release and neural NO where increased NO level in the brain through post translational modification is modulating the level of insulin production. It has been further confirmed that irrespective of origin; brain insulin resistance triggers a cascade of the neurodegeneration phenomenon which can be aggravated by free reactive oxygen species burden, ER stress, metabolic dysfunction, neuorinflammation, reduced cell survival and altered lipid metabolism. Moreover, several studies confirmed that MetS and diabetic sharing common mechanisms in the progression of AD and NDDs where mitochondrial dynamics playing a critical role. Any mutation in mitochondrial DNA, exposure of environmental toxin, high-calorie intake, homeostasis imbalance, glucolipotoxicity is causative factors for mitochondrial dysfunction. These cumulative pleiotropic burdens in mitochondria leads to insulin resistance, increased ROS production; enhanced stress-related enzymes that is directly linked MetS and diabetes in neurodegeneration. Since, the linkup mechanism between mitochondrial dysfunction and disease phenomenon of both MetS and NDDs is quite intriguing, therefore, it is pertinent for the researchers to identify and implement the therapeutic interventions for targeting MetS and NDDs. Herein, we elucidated the pertinent role of MetS induced mitochondrial dysfunction in neurons and their consequences in NDDs. Further, therapeutic potential of well-known biomolecules and chaperones to target altered mitochondria has been comprehensively documented. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

show abstract

“…; Jin et al. ), respectively mimicking the preclinical, early and early to middle stages of AD (Jiang et al. ).…”

Section: Resultsmentioning

confidence: 99%

“…Abnormal SAP102 expression in the hippocampal subregions of APP/PS1 mice In the past decade, because of their early onset of pathological alterations and stable genetic background, APP/PS1 mice have become a very popular AD mouse model (Radde et al 2006;Bilkei-Gorzo, 2014). The APPswe/PS1dE9 double-transgenic mice used in this study develop amyloid plaques at 4 months, and the number of plaques increases with age (Garcia-Alloza et al 2006;Ruan et al 2009;Malm et al 2011;Edwards et al 2014;Jin et al 2015;Kelly et al 2017). Therefore, to investigate and compare dynamic changes in SAP102 expression in the hippocampal subregions, we chose APP/PS1 mice at the time points of 2 months (no plaques; Savonenko et al 2005 We first observed SAP102 expression in WT mice, and the trends were generally the same as those in age-matched rats; the SAP102 fluorescence intensities in the hippocampal subfields of WT mice increased slightly from 2 to 7 months of age (Fig.…”

Section: Sap102 Maintained Higher Levels In the Rat Hippocampal Dg Anmentioning

confidence: 97%

Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages

Liu

et al. 2018

Journal of Anatomy

View full text Add to dashboard Cite

The hippocampus is a structurally and functionally complex brain area that plays important and diverse roles in higher brain functions, such as learning and memory, and mounting evidence indicates that different hippocampal subregions play distinctive roles. The hippocampus is also one of the first regions in the brain to suffer damage in Alzheimer's disease (AD). Synaptic dysfunction in the hippocampus, rather than neuronal loss per se, is paralleled by behavioural and functional deficits in AD. The membrane-associated guanylate kinase (MAGUK) family of proteins, including SAP102, PSD-95, PSD-93 and SAP97, have long been recognized as essential components of the postsynaptic density (PSD) at excitatory synapses. Hippocampal spines are the predominant synaptic transmission sites of excitatory glutamatergic synapses. During postnatal brain development, individual MAGUK members show distinct expression patterns. Although SAP102 has been confirmed as the dominant scaffold protein in neonatal synapses, its expression profiles in adult and ageing rodent hippocampi are discrepant. Furthermore, in AD brains, significantly reduced SAP102 protein levels have been found, suggesting that SAP102 may be related to AD progression; however, the precise mechanism underlying this result remains unclear. Herein, we observed distinct SAP102 expression profiles in the hippocampal CA1, CA3 and DG subregions of rats and APPswe/PS1dE9 (APP/PS1) mice at various ages using immunofluorescence. In Wistar rats, SAP102 was not only highly expressed in the hippocampal subregions of neonatal rats but also maintained relatively high expression levels in adult hippocampi and displayed no obvious decreases in the CA1 and DG subregions of aged rats. Surprisingly, we observed abnormally high SAP102 expression levels in the CA1 stratum moleculare and CA3 stratum polymorphum subregions of 2-month-old APP/PS1 mice, but low SAP102 levels in the DG and CA3 subregions of 7-month-old APP/PS1 mice, reflecting the subregion-specific reactivity and vulnerability of AD mouse models in different disease stages. Our findings provide fundamental data to support the functional differences of SAP102 in different hippocampal subregions during postnatal periods and may serve as the basis for additional functional studies on SAP102 in normal physiological conditions and different stages of AD.

show abstract

CART treatment improves memory and synaptic structure in APP/PS1 mice

Cited by 37 publications

References 37 publications

Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice

Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages

Contact Info

Product

Resources

About