The effect of fish oil treatment on cholesterol metabolism in mouse retina during physiological aging and in Alzheimer's disease model

[I. Jovanović Macura]

83 str.

Biologija - Neurobiologija / Biology - Neurobiology

Mreţnjaĉa je jedini deo centralnog nervnog sistema (CNS) koji moţe direktno da se analizira neinvazivnim metodama, a rane promene u mreţnjaĉi mogu da ukaţu na neurodegenerativne promene u mozgu. S obzirom da je starenje jedan od glavnih faktora rizika za Alchajmerovu bolest (AB) bolje razumevanje promena u mreţnjaĉi povezanih sa starenjem mogu da imaju veliki dijagnostiĉki potencijal. Holesterol ima vaţnu ulogu u procesu starenja, a kod AB reguliše toksiĉnost amiloida-beta (Aβ) i utiĉe na propustljivost krvno-mreţnjaĉne barijere (KMrB). Zato je odrţavanje pravilne homeostaze holesterola izuzetno vaţno. Suplementacija visokim dozama ribljeg ulja (RU) moţe znaĉajno da utiĉe na homeostazu holesterola kao i da odloţi poĉetak ispoljavanja simptoma AB. Ova istraţivanja su imala za cilj da ukaţu na specifiĉne promene koje se dešavaju u mreţnjaĉi u toku fiziološkog i patološkog starenja. Pored toga, evaluiran je i terapeutski efekat kratkotrajnog tretmana visokim dozama RU u presimptomatskoj fazi AB. Ove promene su ispitivane u mreţnjaĉama i pigmentnom epitelu mreţnjaĉe (MPE) ţenki divljeg soja (B6SJLF1 miševi) i 5XFAD animalnog modela AB. TakoĊe, ispitivane su promene na krvnim sudovima nastale nakon nagomilavanja Aβ u starenju kao i nakon tretmana RU. S obzirom da je metabolizam holesterola u mreţnjaĉi, kao i u mozgu, kod 5XFAD miševa atenutiran, tretman RU nije pokazao znaĉajan efekat na regulaciju homeostaze holesterola. Specifiĉno nakupljanje Aβ u krvnim sudovima mreţnjaĉe pokazano kod AB nastaje usled povećane transcitoze i disfunkcionalnog glimfatiĉkog sistema. Kratkotrajni tretman (3 nedelje) visokim dozama RU je ispoljio snaţan protektivni efekat na propustljivost KMrB i doveo do znaĉajnog smanjenja akumulacije Aβ na krvnim sudovima mreţnjaĉe (za 22%). Dobijeni rezultati pokazuju da tretman visokim dozama RU moţe imati protektivni efekat na funkciju KMrB i ukazuje na potencijal RU u adjuvantnim i profilaktiĉkim terapijama u cilju jaĉanja krvnih sudova.

The retina is the only part of the central nervous system (CNS) that can be directly analyzed by non-invasive methods, and early changes in the retina can indicate neurodegenerative changes in the brain. Given that aging is one of the major risk factors for Alzheimer's disease (AD), a better understanding of age-related changes in the retina may have great diagnostic potential. Cholesterol plays an important role in the aging process, and in AB it regulates the toxicity of amyloid-beta (Aβ) and affects the permeability of the blood-retinal barrier (BRB). That is why maintaining proper cholesterol homeostasis is extremely important. Supplementation with high doses of fish oil (FO) can significantly affect cholesterol homeostasis as well as delay the onset of AB symptoms. These studies aimed to indicate the specific changes that occur in the retina during physiological and pathological aging. In addition, the therapeutic effect of short-term treatment with high doses of FO in the presymptomatic phase of AB was also evaluated. These changes were examined in the retinal pigment epithelium (MPE) of wild-type female mice (B6SJLF1 mice) and the 5XFAD animal model AB. Also, the changes in blood vessels that occurred after the accumulation of Aβ in aging as well as after FO treatment were investigated. Given that cholesterol metabolism is attenuated in the retina, as well as in the brain of 5XFAD mice, FO treatment did not show a significant effect on the regulation of cholesterol homeostasis. The specific accumulation of Aβ in retinal blood vessels shown in AD is due to increased transcytosis and a dysfunctional glymphatic system. Short-term treatment (3 weeks) with high doses of FO exerted a strong protective effect on BRB permeability and led to a significant reduction of Aβ accumulation in retinal blood vessels (by 22%). The obtained results show that treatment with high doses of FO can have a protective effect on BRB function and indicate the potential of FO in adjuvant and prophylactic therapies aimed at strengthening blood vessels.

mrežnjaĉa, MPE, starenje, Alchajmerova bolest, holesterol, transcitoza, glimfatiĉki sistem, riblje ulje

retina, retinal pigment epithelium, aging, Alzheimer's disease, cholesterol, transcytosis, glymphatic system, fish oil

577.25:616.8(043.3)

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