Zussy Charleine, John Rijo, Urgin Théo, Otaegui Léa, Vigor Claire, Acar Niyazi, Canet Geoffrey, Vitalis Mathieu, Morin Françoise, Planel Emmanuel, Oger Camille, Durand Thierry, Rajshree Shinde L, Givalois Laurent, Devarajan Padma V, Desrumaux Catherine
MMDN, University Montpellier, EPHE, INSERM, 34095 Montpellier, France.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Deemed University, Mumbai 400019, India.
Antioxidants (Basel). 2022 Apr 25;11(5):838. doi: 10.3390/antiox11050838.
Polyunsaturated fatty acids (PUFAs) are a class of fatty acids that are closely associated with the development and function of the brain. The most abundant PUFA is docosahexaenoic acid (DHA, 22:6 -3). In humans, low plasmatic concentrations of DHA have been associated with impaired cognitive function, low hippocampal volumes, and increased amyloid deposition in the brain. Several studies have reported reduced brain DHA concentrations in Alzheimer's disease (AD) patients' brains. Although a number of epidemiological studies suggest that dietary DHA consumption may protect the elderly from developing cognitive impairment or dementia including AD, several review articles report an inconclusive association between omega-3 PUFAs intake and cognitive decline. The source of these inconsistencies might be because DHA is highly oxidizable and its accessibility to the brain is limited by the blood-brain barrier. Thus, there is a pressing need for new strategies to improve DHA brain supply. In the present study, we show for the first time that the intranasal administration of nanovectorized DHA reduces Tau phosphorylation and restores cognitive functions in two complementary murine models of AD. These results pave the way for the development of a new approach to target the brain with DHA for the prevention or treatment of this devastating disease.
多不饱和脂肪酸（PUFAs）是一类与大脑发育和功能密切相关的脂肪酸。最丰富的多不饱和脂肪酸是二十二碳六烯酸（DHA，22:6 -3）。在人类中，血浆中DHA浓度低与认知功能受损、海马体积减小以及大脑中淀粉样蛋白沉积增加有关。多项研究报告称，阿尔茨海默病（AD）患者大脑中的DHA浓度降低。尽管一些流行病学研究表明，通过饮食摄入DHA可能会保护老年人免受包括AD在内的认知障碍或痴呆症的影响，但几篇综述文章报告称，ω-3多不饱和脂肪酸的摄入量与认知衰退之间的关联尚无定论。这些不一致的原因可能是DHA极易氧化，并且其进入大脑的途径受到血脑屏障的限制。因此，迫切需要新的策略来改善大脑中DHA的供应。在本研究中，我们首次表明，经鼻给予纳米载体化的DHA可减少两种互补的AD小鼠模型中的 Tau 蛋白磷酸化并恢复认知功能。这些结果为开发一种用DHA靶向大脑以预防或治疗这种毁灭性疾病的新方法铺平了道路。
