Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons

Wang, Desheng; Zheng, Wei

doi:10.1016/j.brainres.2015.06.049

Cited by 25 publications

(20 citation statements)

References 50 publications

(78 reference statements)

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“…Increased cholesterol levels in the fetal brain may have altered synaptic plasticity in memory‐related brain structures ( e.g. , hippocampus (38)), thus resulting in enhanced memory function, as previously reported in young rats (33).…”

Section: Discussionmentioning

confidence: 54%

“…We therefore speculate that the elevated levels of circulating cholesterol in the sows during late gestation were positively associated with increased cholesterol levels in the fetal brain in our study. Increased cholesterol levels in the fetal brain may have altered synaptic plasticity in memory-related brain structures (e.g., hippocampus (38)), thus resulting in enhanced memory function, as previously reported in young rats (33).…”

Section: Discussionmentioning

confidence: 55%

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Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels

et al. 2016

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Maternal obesity and perinatal high‐fat diets are known to affect cognitive development. We examined the effects of late prenatal and/or early postnatal exposure to a Western‐type diet, high in both fat and refined sugar, on the cognition of pigs (Sus scrofa) in the absence of obesity. Thirty‐six sows and their offspring were assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement, with 8 wk prenatal and 8 wk postnatal exposure to a Western diet (enriched in fat, sucrose, and cholesterol) or control diets as factors. Compared to controls, piglets exposed to the prenatal Western diet showed enhanced working and reference memory during the acquisition and reversal phases of a spatial hole‐board task. Mothers fed the prenatal Western diet had higher prepartum blood cholesterol and free fatty acid levels. Postnatal exposure to the Western diet did not affect piglet cognitive performance, but it did increase postpartum maternal and postweaning piglet cholesterol levels. The Western diet had no effect on maternal or offspring insulin sensitivity or leptin levels. In conclusion, a prenatal Western diet improved memory function in pigs, which was paired with changes in prepartum maternal blood cholesterol levels. These findings highlight the key role of late fetal nutrition for long‐term programming of cognition.—Clouard, C., Kemp, B., Val‐Laillet, D., Gerrits, W. J. J., Bartels, A. C., Bolhuis, J. E. Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels. FASEB J. 30, 2466‐2475 (2016). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 55%

Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels

et al. 2016

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“…Many studies have focused on cholesterol or cholesterol esters as risk factors for AD, and researchers are interested in how cholesterol levels affect AD by regulating Aβ production [29,[37][38][39]. Taken together, both directions suggest a mutual regulation PLOS COMPUTATIONAL BIOLOGY mechanism between cholesterol biosynthesis and Aβ production ( Fig 6E) that may play an essential role in normal biological function, such as synapse plasticity [40][41][42][43][44][45]. However, excessive production of Aβ causes toxic oligomers, plaques and activates brain inflammatory systems [46,47].…”

Section: Discussionmentioning

confidence: 99%

A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular progress of Alzheimer's disease

Park

Kim

et al. 2020

PLoS Comput Biol

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Next-generation sequencing (NGS) technology has become a powerful tool for dissecting the molecular and pathological signatures of a variety of human diseases. However, the limited availability of biological samples from different disease stages is a major hurdle in studying disease progressions and identifying early pathological changes. Deep learning techniques have recently begun to be applied to analyze NGS data and thereby predict the progression of biological processes. In this study, we applied a deep learning technique called generative adversarial networks (GANs) to predict the molecular progress of Alzheimer's disease (AD). We successfully applied GANs to analyze RNA-seq data from a 5xFAD mouse model of AD, which recapitulates major AD features of massive amyloid-β (Aβ) accumulation in the brain. We examined how the generator is featured to have specific-sample generation and biological gene association. Based on the above observations, we suggested virtual disease progress by latent space interpolation to yield the transition curves of various genes with pathological changes from normal to AD state. By performing pathway analysis based on the transition curve patterns, we identified several pathological processes with progressive changes, such as inflammatory systems and synapse functions, which have previously been demonstrated to be involved in the pathogenesis of AD. Interestingly, our analysis indicates that alteration of cholesterol biosynthesis begins at a very early stage of AD, suggesting that it is the first effect to mediate the cholesterol metabolism of AD downstream of Aβ accumulation. Here, we suggest that GANs are a useful tool to study disease progression, leading to the identification of early pathological signatures.

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“…Slices were incubated at 22°C in artificial cerebrospinal fluid (ACSF; 124 mM NaCl, 3 mM KCl, 1.2 mM MgSO 4 , 2.1 mM CaCl 2 , 1.4 mM Na 2 PO 4 , 26 mM NaHCO 3 , 20 mM dextrose, pH 7.4) saturated with 95% O 2 /5% CO 2 . After 1‐h incubation, slices were transferred into a recording chamber for electrophysiological measurements as previously described (Wang and Zheng ).…”

Section: Methodsmentioning

confidence: 99%

Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus

Hunsberger

Wang

Petrisko

et al. 2016

Journal of Neurochemistry

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Peripheral infections increase the propensity and severity of seizures in susceptible populations. We have previously shown that intraperitoneal injection of a viral mimic, polyinosinicpolycytidylic acid (PIC), elicits hypersusceptibility of mice to kainic acid (KA)-induced seizures. This study was undertaken to determine whether this seizure hypersusceptibility entails alterations in glutamate signaling. Female C57BL/6 mice were intraperitoneally injected with PIC, and after 24 h, glutamate homeostasis in the hippocampus was monitored using the enzyme-based microelectrode arrays. PIC challenge robustly increased the level of resting extracellular glutamate. While presynaptic potassium-evoked glutamate release was not affected, glutamate uptake was profoundly impaired and non-vesicular glutamate release was augmented, indicating functional alterations of astrocytes. Electrophysiological examination of hippocampal slices from PIC-challenged mice revealed a several fold increase in the basal synaptic transmission as compared to control slices. PIC challenge also increased the probability of pre-synaptic glutamate release as seen from a reduction of paired-pulse facilitation and synaptic plasticity as seen from an enhancement of long-term potentiation. Altogether, our results implicate a dysregulation of astrocytic glutamate metabolism and an alteration of excitatory synaptic transmission as the underlying mechanism for the development of hippocampal hyperexcitability, and consequently seizure hypersusceptibility following peripheral PIC challenge.

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Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons

Cited by 25 publications

References 50 publications

Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels

Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels

A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular progress of Alzheimer's disease

Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus

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