The Important Role of Lipids in Cognitive Impairment

2011 ◽  
pp. 206-211
Author(s):  
Yu Jia ◽  
Zheng Chen ◽  
Jiangyang Lu ◽  
Liu Tingting ◽  
Zhou Liang ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Memory Function ◽  
Pyramidal Cells ◽  
Cholesterol Homeostasis ◽  
Neonatal Lethality ◽  
Somatic Gene ◽  
Current Knowledge Base ◽  
Somatic Gene Transfer ◽  
The Brain

The current knowledge base on circulating serum and plasma risk factors of the cognitive decline of degenerative Alzheimer’s Disease is linked to cholesterol homeostasis and lipoprotein disturbances (i.e., total cholesterol, 24S-hydroxy-cholesterol, lipoprotein(a), or apolipoprotein E. Lipoprotein lipase (LPL) is also expressed in the brain, with the highest levels found in the pyramidal cells of the hippocampus, suggesting a possible role for LPL in the regulation of cognitive function. Little is currently known, however, about the specific role of LPL in the brain. The authors of this chapter have generated an LPL-deficient mouse model that was rescued from neonatal lethality by somatic gene transfer. The levels of the presynaptic marker synaptophysin were reduced in the hippocampus while the levels of the post-synaptic marker PSD-95 remained unchanged in the LPL-deficient mice. The decreased frequency of mEPSC in LPL-deficient neurons indicated that the number of presynaptic vesicles was decreased, which was consistent with the decreases observed in the numbers of total vesicles and docking vesicles. These findings indicate that LPL plays an important role in learning and memory function, possibly by influencing presynaptic function.

The Important Role of Lipids in Cognitive Impairment

2013 ◽  
pp. 268-272
Author(s):  
Jia Yu ◽  
Zheng Chen ◽  
Jiangyang Lu ◽  
Tingting Liu ◽  
Liang Zhou ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Memory Function ◽  
Pyramidal Cells ◽  
Cholesterol Homeostasis ◽  
Neonatal Lethality ◽  
Somatic Gene ◽  
Current Knowledge Base ◽  
Somatic Gene Transfer ◽  
The Brain

The current knowledge base on circulating serum and plasma risk factors of the cognitive decline of degenerative Alzheimer’s Disease is linked to cholesterol homeostasis and lipoprotein disturbances (i.e., total cholesterol, 24S-hydroxy-cholesterol, lipoprotein(a), or apolipoprotein E. Lipoprotein lipase (LPL) is also expressed in the brain, with the highest levels found in the pyramidal cells of the hippocampus, suggesting a possible role for LPL in the regulation of cognitive function. Little is currently known, however, about the specific role of LPL in the brain. The authors of this chapter have generated an LPL-deficient mouse model that was rescued from neonatal lethality by somatic gene transfer. The levels of the presynaptic marker synaptophysin were reduced in the hippocampus while the levels of the post-synaptic marker PSD-95 remained unchanged in the LPL-deficient mice. The decreased frequency of mEPSC in LPL-deficient neurons indicated that the number of presynaptic vesicles was decreased, which was consistent with the decreases observed in the numbers of total vesicles and docking vesicles. These findings indicate that LPL plays an important role in learning and memory function, possibly by influencing presynaptic function.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

scholarly journals The Gut Ecosystem: A Critical Player in Stroke

2020 ◽  
Author(s):  
Rosa Delgado Jiménez ◽  
Corinne Benakis
Keyword(s):  
Current Knowledge ◽  
Critical Factor ◽  
Intestinal Microbiome ◽  
Brain Disorders ◽  
Therapeutic Approaches ◽  
Health And Disease ◽  
Brain Stroke ◽  
The Brain ◽  
Improve Patient

AbstractThe intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

scholarly journals Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

2020 ◽  
Vol 21 (22) ◽  
pp. 8767
Author(s):  
Nicole Jacqueline Jensen ◽  
Helena Zander Wodschow ◽  
Malin Nilsson ◽  
Jørgen Rungby
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Brain Metabolism ◽  
Ketone Bodies ◽  
Current Knowledge ◽  
Ketogenic Diets ◽  
Cognitive Benefits ◽  
The Brain

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

Age and Dietary Vitamin C Intake Affect Brain Physiology in Genetically Modified Mice Expressing Human Lipoprotein(A) and Unable to Synthesize Vitamin C

2021 ◽  
Vol 14 ◽  
Author(s):  
Lei Shi ◽  
Aleksandra Niedzwiecki ◽  
Matthias Rath
Keyword(s):  
Vitamin C ◽  
Oxidative Damage ◽  
Critical Role ◽  
Cholesterol Homeostasis ◽  
Dietary Vitamin ◽  
Brain Health ◽  
Lipoprotein A ◽  
Vitamin C Deficiency ◽  
The Brain

Aims: Lipoprotein (a) deposition in coronary vascular plaques and cerebral vessels is a recognized risk factor for cardiovascular disease, and research supports its role as a “repair factor” in vascular walls weakened by vitamin C deficiency. Background: Humans depend on dietary vitamin C as an important antioxidant, and as a cofactor in collagen synthesis, yet are prone to vitamin C deficiency. The brain is the one with the highest vitamin C content, due to its high oxygen consumption and oxidative stress. It has been shown that brain aging is accompanied by accumulated oxidative damage, which can lead to memory decline and neurological diseases. Objective: Our transgenic mouse, Gulo (-/-); Lp(a)+, presents a unique model for the study of key aspects of human metabolism with respect to a lack of internal vitamin C synthesis and the production of human Lipoprotein(a). Method: This mouse model was used in our study to investigate the effects of prolonged intake of low and high levels of vitamin C, at different ages, on oxidative damage, cholesterol levels and Lipoprotein(a) deposition in the brain. Result: The results show that a long-term high vitamin C intake is important in maintaining brain cholesterol homeostasis and preventing oxidative damage in Gulo(-/-);Lp(a)+ mice as they age. Moreover, we observed that the formation of brain Lipoprotein(a) deposits was negatively correlated with brain level of vitamin C, thereby confirming its role as a stability factor for an impaired extracellular matrix. Conclusion: Our study emphasizes the critical role of vitamin C in protecting brain health as we age. Other: Our findings show that optimal vitamin C intake from early life to old age is important in brain health to prevent oxidative stress damage and to maintain cholesterol homeostasis in the brain. More importantly, negative correlation between brain ascorbic levels and the formation of Lp(a) deposit on the choroid plexus further emphasizes the critical role of vitamin C in protecting brain health throughout the normal aging process.

scholarly journals The Role of Gut Microbiota on Cholesterol Metabolism in Atherosclerosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8074
Author(s):  
Margaret Vourakis ◽  
Gaétan Mayer ◽  
Guy Rousseau
Keyword(s):  
Cardiovascular Health ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Short Chain Fatty Acids ◽  
Developed Countries ◽  
Current Data ◽  
Cholesterol Homeostasis ◽  
Intestinal Microbes ◽  
Inflammatory Processes

Hypercholesterolemia plays a causal role in the development of atherosclerosis and is one of the main risk factors for cardiovascular disease (CVD), the leading cause of death worldwide especially in developed countries. Current data show that the role of microbiota extends beyond digestion by being implicated in several metabolic and inflammatory processes linked to several diseases including CVD. Studies have reported associations between bacterial metabolites and hypercholesterolemia. However, such associations remain poorly investigated and characterized. In this review, the mechanisms of microbial derived metabolites such as primary and secondary bile acids (BAs), trimethylamine N-oxide (TMAO), and short-chain fatty acids (SCFAs) will be explored in the context of cholesterol metabolism. These metabolites play critical roles in maintaining cardiovascular health and if dysregulated can potentially contribute to CVD. They can be modulated via nutritional and pharmacological interventions such as statins, prebiotics, and probiotics. However, the mechanisms behind these interactions also remain unclear, and mechanistic insights into their impact will be provided. Therefore, the objectives of this paper are to present current knowledge on potential mechanisms whereby microbial metabolites regulate cholesterol homeostasis and to discuss the feasibility of modulating intestinal microbes and metabolites as a novel therapeutic for hypercholesterolemia.

scholarly journals Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2353
Author(s):  
Maja Potokar ◽  
Jernej Jorgačevski
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Proteins ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Plectin, a high-molecular-mass cytolinker, is abundantly expressed in the central nervous system (CNS). Currently, a limited amount of data about plectin in the CNS prevents us from seeing the complete picture of how plectin affects the functioning of the CNS as a whole. Yet, by analogy to its role in other tissues, it is anticipated that, in the CNS, plectin also functions as the key cytoskeleton interlinking molecule. Thus, it is likely involved in signalling processes, thereby affecting numerous fundamental functions in the brain and spinal cord. Versatile direct and indirect interactions of plectin with cytoskeletal filaments and enzymes in the cells of the CNS in normal physiological and in pathologic conditions remain to be fully addressed. Several pathologies of the CNS related to plectin have been discovered in patients with plectinopathies. However, in view of plectin as an integrator of a cohesive mesh of cellular proteins, it is important that the role of plectin is also considered in other CNS pathologies. This review summarizes the current knowledge of plectin in the CNS, focusing on plectin isoforms that have been detected in the CNS, along with its expression profile and distribution alongside diverse cytoskeleton filaments in CNS cell types. Considering that the bidirectional communication between neurons and glial cells, especially astrocytes, is crucial for proper functioning of the CNS, we place particular emphasis on the known roles of plectin in neurons, and we propose possible roles of plectin in astrocytes.

Role of ABC transporters in the pathology of Alzheimer’s disease

2017 ◽  
Vol 28 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Yan Zhao ◽  
Deren Hou ◽  
Xialu Feng ◽  
Fangbo Lin ◽  
Jing Luo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Present Article ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Large Family ◽  
Cholesterol Homeostasis

AbstractThe ATP-binding cassette (ABC) transporter superfamily is a large family of proteins that transport specific molecules across membranes. These proteins are associated with both cholesterol metabolism and Alzheimer’s disease (AD). Cholesterol homeostasis has a key role in AD, and ABC transporters are important mediators of lipid transportation. Emerging evidence suggests that decreased expression and hypofunction of ABC transporters are crucial to the occurrence and development of AD. In the present article, we review the current knowledge regarding ABC transporters and speculate on their role in the pathogenesis of AD.

scholarly journals The role of neuropeptide somatostatin in the brain and its application in treating neurological disorders

2021 ◽  
Author(s):  
You-Hyang Song ◽  
Jiwon Yoon ◽  
Seung-Hee Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Cortical Circuits ◽  
Protein Marker ◽  
And Function ◽  
Novel Drug ◽  
The Brain

AbstractSomatostatin (SST) is a well-known neuropeptide that is expressed throughout the brain. In the cortex, SST is expressed in a subset of GABAergic neurons and is known as a protein marker of inhibitory interneurons. Recent studies have identified the key functions of SST in modulating cortical circuits in the brain and cognitive function. Furthermore, reduced expression of SST is a hallmark of various neurological disorders, including Alzheimer’s disease and depression. In this review, we summarize the current knowledge on SST expression and function in the brain. In particular, we describe the physiological roles of SST-positive interneurons in the cortex. We further describe the causal relationship between pathophysiological changes in SST function and various neurological disorders, such as Alzheimer’s disease. Finally, we discuss potential treatments and possibility of novel drug developments for neurological disorders based on the current knowledge on the function of SST and SST analogs in the brain derived from experimental and clinical studies.

scholarly journals Central Regulation of Metabolism by Growth Hormone

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 129
Author(s):  
Jose Donato ◽  
Frederick Wasinski ◽  
Isadora C. Furigo ◽  
Martin Metzger ◽  
Renata Frazão
Keyword(s):  
Growth Hormone ◽  
Energy Homeostasis ◽  
Current Knowledge ◽  
Metabolic Stress ◽  
Wide Distribution ◽  
Tissue Growth ◽  
Neuronal Populations ◽  
Hypothalamic Nuclei ◽  
The Brain

Growth hormone (GH) is secreted by the pituitary gland, and in addition to its classical functions of regulating height, protein synthesis, tissue growth, and cell proliferation, GH exerts profound effects on metabolism. In this regard, GH stimulates lipolysis in white adipose tissue and antagonizes insulin’s effects on glycemic control. During the last decade, a wide distribution of GH-responsive neurons were identified in numerous brain areas, especially in hypothalamic nuclei, that control metabolism. The specific role of GH action in different neuronal populations is now starting to be uncovered, and so far, it indicates that the brain is an important target of GH for the regulation of food intake, energy expenditure, and glycemia and neuroendocrine changes, particularly in response to different forms of metabolic stress such as glucoprivation, food restriction, and physical exercise. The objective of the present review is to summarize the current knowledge about the potential role of GH action in the brain for the regulation of different metabolic aspects. The findings gathered here allow us to suggest that GH represents a hormonal factor that conveys homeostatic information to the brain to produce metabolic adjustments in order to promote energy homeostasis.

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