Short-term exposure to dietary cholesterol is associated with downregulation of interleukin-15, reduced thigmotaxis and memory impairment in mice

Mayagoitia, Karina; Shin, Sam; Rubini, Marsilio; Siebold, Lorraine; Wilson, Christopher G.; Bellinger, Denise L.; Figueroa, Johnny D.; Soriano, Salvador

doi:10.1016/j.bbr.2020.112779

Cited by 5 publications

(5 citation statements)

References 70 publications

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“… 55 , 56 In addition, previous investigations have noted that the cognitive and behavioural phenotypes of mice are associated with reduced levels of interleukin-15. 57-59 CSF1R is a receptor mainly expressed in microglia which regulates microglial activation and survival. Supplementation of CSF1 can improve the deposition of Aβ plaques in 5xFAD mouse brain.…”

Section: Discussionmentioning

confidence: 99%

Maf1 loss regulates spinogenesis and attenuates cognitive impairment in Alzheimer’s disease

Han,

Chen,

et al. 2024

Brain

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. Synaptic dysfunction has appeared in the early stage of AD and is significantly correlated with cognitive impairment. However, the specific regulatory mechanism remains unclear. Here we found upregulated Maf1 transcription factor in AD, and Maf1 conditional knockout in AD transgenic mice restored learning and memory function. Downregulation of Maf1 reduced intraneuronal Ca2+ concentration and restored neuronal synaptic morphology. We also demonstrated that Maf1 regulates the expression of NMDAR1 by binding to the promoter region of Grin1, further regulating calcium homeostasis and synaptic remodeling in neurons. Therefore, our results clarified the important role and mechanism of the Maf1-NMDAR1 signaling pathway in the stability of the synaptic structure, neuronal function, and behavior during the pathogenesis of AD, serving as a potential diagnostic and therapeutic target for the early onset of AD.

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Section: Discussionmentioning

confidence: 99%

Maf1 loss regulates spinogenesis and attenuates cognitive impairment in Alzheimer’s disease

Han,

Chen,

et al. 2024

Brain

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“…Moreover, LPH-treated mice showed similar thigmotaxis to the SD group. This behavior is a well-established indicator of animal anxiety and fear [ 68 , 69 ]. This fact is consistent with the results observed in the EPM, strengthening the protective effect of LPH on WD-induced anxiety.…”

Section: Discussionmentioning

confidence: 99%

“…High levels of oxidative stress and inflammation in the brain have been widely reported to be two of the main contributing factors involved in the development of anxiety [ 42 , 43 , 44 ]. Moreover, recent studies have shown a strong link between high cholesterol levels and anxiety [ 69 ]. Our group has previously shown that LPH exerts anti-inflammatory, antioxidant, and lipid-lowering effects both in ApoE −/− mice [ 47 , 73 ] and humans [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

A Lupin (Lupinus angustifolius) Protein Hydrolysate Exerts Anxiolytic-Like Effects in Western Diet-Fed ApoE−/− Mice

Santos-Sánchez

Ponce-España

López-Garcı́a

et al. 2022

IJMS

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Anxiety is the most prevalent psychiatric disorder worldwide, causing a substantial economic burden due to the associated healthcare costs. Given that commercial anxiolytic treatments may cause important side effects and have medical restrictions for prescription and high costs, the search for new natural and safer treatments is gaining attention. Since lupin protein hydrolysate (LPH) has been shown to be safe and exert anti-inflammatory and antioxidant effects, key risk factors for the anxiety process and memory impairment, we evaluated in this study the potential effects of LPH on anxiety and spatial memory in a Western diet (WD)-induced anxiety model in ApoE−/− mice. We showed that 20.86% of the 278 identified LPH peptides have biological activity related to anxiolytic/analgesic effects; the principal motifs found were the following: VPL, PGP, YL, and GQ. Moreover, 14 weeks of intragastrical LPH treatment (100 mg/kg) restored the WD-induced anxiety effects, reestablishing the anxiety levels observed in the standard diet (SD)-fed mice since they spent less time in the anxiety zones of the elevated plus maze (EPM). Furthermore, a significant increase in the number of head dips was recorded in LPH-treated mice, which indicates a greater exploration capacity and less fear due to lower levels of anxiety. Interestingly, the LPH group showed similar thigmotaxis, a well-established indicator of animal anxiety and fear, to the SD group, counteracting the WD effect. This is the first study to show that LPH treatment has anxiolytic effects, pointing to LPH as a potential component of future nutritional therapies in patients with anxiety.

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“…180 Hypercholesterolemia produces microglial activation, and high-cholesterol diet promotes inflammatory responses. 181 Furthermore, oxysterols are involved in glial activation, 182 where LXRs can modulate cholesterol and oxysterol metabolisms through repressing neuroinflammation. 183 The inflammarafts are cholesterol-enriched lipid domains that are thought to act as a platform mediating the cellular inflammatory response, conceivably being regulated by cholesterol and sphingolipid metabolism 184 and ApoE 185 (Fig.…”

Section: Cholesterol In Neuroinflammationmentioning

confidence: 99%

“…Indeed, Npc1 −/− mice displayed dysregulated expression of inflammatory mediators 180 . Hypercholesterolemia produces microglial activation, and high‐cholesterol diet promotes inflammatory responses 181 . Furthermore, oxysterols are involved in glial activation, 182 where LXRs can modulate cholesterol and oxysterol metabolisms through repressing neuroinflammation 183 .…”

Section: Cholesterol In Pdmentioning

confidence: 99%

The Role of Cholesterol in α‐Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease

2020

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A BS TRACT: Parkinson's disease (PD) is a progressive neurodegenerative disease where dopaminergic neurons in the substantia nigra are lost, resulting in a decrease in striatal dopamine and, consequently, motor control. Dopaminergic degeneration is associated with the appearance of Lewy bodies, which contain membrane structures and proteins, including α-synuclein (α-Syn), in surviving neurons. PD displays a multifactorial pathology and develops from interactions between multiple elements, such as age, environmental conditions, and genetics. Mutations in the GBA1 gene represent one of the major genetic risk factors for PD. This gene encodes an essential lysosomal enzyme called β-glucocerebrosidase (GCase), which is responsible for degrading the glycolipid glucocerebroside into glucose and ceramide. GCase can generate glucosylated cholesterol via transglucosylation and can also degrade the sterol glucoside. Although the molecular mechanisms that predispose an individual to neurodegeneration remain unknown, the role of cholesterol in PD pathology deserves consideration. Disturbed cellular cholesterol metabolism, as reflected by accumulation of lysosomal cholesterol in GBA1-associated PD cellular models, could contribute to changes in lipid rafts, which are necessary for synaptic localization and vesicle cycling and modulation of synaptic integrity. α-Syn has been implicated in the regulation of neuronal cholesterol, and cholesterol facilitates interactions between α-Syn oligomers. In this review, we integrate the results of previous studies and describe the cholesterol landscape in cellular homeostasis and neuronal function. We discuss its implication in α-Syn and Lewy body pathophysiological mechanisms underlying PD, focusing on the role of GCase and cholesterol.

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Short-term exposure to dietary cholesterol is associated with downregulation of interleukin-15, reduced thigmotaxis and memory impairment in mice

Cited by 5 publications

References 70 publications

Maf1 loss regulates spinogenesis and attenuates cognitive impairment in Alzheimer’s disease

Maf1 loss regulates spinogenesis and attenuates cognitive impairment in Alzheimer’s disease

A Lupin (Lupinus angustifolius) Protein Hydrolysate Exerts Anxiolytic-Like Effects in Western Diet-Fed ApoE−/− Mice

The Role of Cholesterol in α‐Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease

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