Uticaj starenja i dugotrajne dijetalne restrikcije na metabolizam holesterola u prednjem mozgu pacova

Abstract

Starenje centralnog nervnog sistema (CNS) praćeno je brojnim promenama koje dovode do narušavanja nervnih funkcija, pre svega kontrole motorike i kognitivnih sposobnosti. Smatra se da su kognitivni poremećaji tokom starenja posledica smanjene sinaptičke plastičnosti, naročito u korteksu i hipokampusu, regionima mozga izuzetno važnim za procese učenja i pamćenja. Najvažniji faktor sredine kojim se može uticati na starenje uopšte, a samim tim i na starenje mozga je režim redukovane ishrane, bez pothranjenosti. Pored toga što se već nekoliko decenija zna da redukovana ishrana produžava životni vek mnogih vrsta, uključujući i sisare, pokazano je da ona odlaže i ublažava starosno zavisne promene u nervnom sistemu. Holesterol je najzastupljeniji lipid u ćelijama sisara. Učestvujući u izgradnji fosfolipidnog dvosloja bioloških mambrana, on reguliše njihovu fluidnost, propustljivost i rigidnost, a samim tim i funkcionalna svojstva membranskih proteina, poput jonskih kanala i transmiterskih receptora. Metabolizam holesterola predstavlja važan aspekt sinaptičke plastičnosti, jer je pokazano da je holesterol neophodan za biogenezu i transport sinaptičkih vezikula, kao i za prvilnu funkcionalnu organizaciju lipidnih ostvaca. Od svih organa u telu, mozak sadrži najviše holesterola. Održavanje homeostaze holesterola neophodno je za normalno i neometano funkcionisanje CNS...

Ageing of the central nervous system is associated with a number of changes that disturb nerve function, especially motor control and cognitive abilities. It is believed that cognitive disorders in aging are consequence of reduced synaptic plasticity, especially in the cortex and hippocampus, brain regions extremely important for learning and memory processes. Dominant factor that can influence aging in general, and therefore the aging of the brain is reduced diet regime, without malnutrition. In addition to being known for decades that reduced caloric intake prolongs life span of many species, including mammals, it is shown that it delays and alleviates age-dependent changes.Cholesterol is the most abundant lipid in mammalian cells. By participating in the construction of phospholipid bilayer of biological membranes, it regulates their fluidity, permeability and rigidity, and consequently the functional properties of membrane proteins, such as ion channels and transmmitters receptors. Cholesterol metabolism represents one aspect of synaptic plasticity, as has been shown that cholesterol is essential for biogenesis of synaptic vesicles, and vesicle transport, as well as for proper functional organization of lipid rafts. The brain contains the most cholesterol of all the organs in the body. Maintenance of cholesterol homeostasis is essential for proper functioning of the central nervous system...