phytosterols and Multiple-Sclerosis

In mammals, the central nervous system (CNS) is the most cholesterol rich organ by weight. Cholesterol metabolism is tightly regulated in the CNS and all cholesterol available is synthesized in situ. Deficits in cholesterol homeostasis at the level of synthesis, transport, or catabolism result in severe disorders featured by neurological disability. Recent studies indicate that a disturbed cholesterol metabolism is involved in CNS disorders, such as Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In contrast to circulating cholesterol, dietary plant sterols, can cross the blood-brain barrier and accumulate in the membranes of CNS cells. Plant sterols are well-known for their ability to lower circulating cholesterol levels. The finding that they gain access to the CNS has fueled research focusing on the physiological roles of plant sterols in the healthy and diseased CNS. To date, both beneficial and detrimental effects of plant sterols on CNS disorders are defined. In this review, we discuss recent findings regarding the impact of plant sterols on homeostatic and pathogenic processes in the CNS, and elaborate on the therapeutic potential of plant sterols in CNS disorders.

Topics: Animals; Central Nervous System Diseases; Humans; Multiple Sclerosis; Phytosterols

Using experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), the objective of this study was to examine the effect of phytosterol (PS) administration on inflammation-based EAE development.. Female SJL mice were orally administered PS prior to disease induction and maintained throughout the experiment. EAE was induced with antigenic peptide (PLP(131-155)). Mice were clinically scored for disease and euthanized for biochemical and histological analysis of inflammation.. PS delayed onset of EAE development by 2 days and decreased disease severity by 55%. Brain histological analysis revealed an 82% decrease in central nervous system (CNS) inflammatory infiltration and a 48% decrease in demyelination in PS-treated mice versus control. Immunohistochemistry (IHC) showed a 35% reduction in macrophages entering brains of PS-treated mice. Anti-inflammatory interleukin (IL)-10 was up-regulated by 10%, while pro-inflammatory CCL2 was inhibited by 50% with PS treatment. Additionally, PS slightly decreased other pro-inflammatory factors, such as tumor necrosis factor (TNF)-α, IL-6, and interferon (IFN)-γ.. PS protects against development of EAE by reducing infiltration and inflammatory activity of immune cells into CNS of treated mice, thereby decreasing demyelination associated with EAE. These results provide evidence to support PS as a preventative agent that helps to protect against the development of inflammation-driven disease, such as MS.

Topics: Animal Feed; Animals; Brain; Central Nervous System; Encephalomyelitis, Autoimmune, Experimental; Female; Immunohistochemistry; Inflammation; Lymphocytes; Macrophages; Mice; Multiple Sclerosis; Peptides; Phytosterols; Time Factors