Nervonic acid, a viable treatment option for alleviating stroke and its associated post-stroke depression behaviors

Nervonic acid (C24:1 Δ15, NA) is a very long-chain monounsaturated fatty acid found in various organisms, including microalgae, mammals, fish, and oleaginous plants[1]. It is involved in several biological processes such as membrane formation, apoptosis, and neurotransmitter transmission[2]. Previous studies have revealed that NA plays an intrinsic role in brain development. Furthermore, the supplementation of NA can alleviate many diseases, including cancer, diabetes, obesity, and neurological disorders such as stroke, Parkinson’s disease, and schizophrenia[3,4]. Naturally, NA has been synthesized by numerous microalgae, fungi, and plants. Recently, NA could be abundantly synthesized by genetically engineered microorganisms[5,6].

In this study, they investigated the efficacy of NA in treating ischemia/reperfusion and poststroke events with a rat model. Specifically, there were significant reductions in the infarct area, cell death, and neuronal swelling after NA treatment, and the improvement of cerebral blood flow was also observed on day five after middle cerebral artery occlusion. Moreover, NA treatment led to the upregulation of Brain-Derived Neurotrophic Factor and Myelin Basic Protein genes. What interests them even more is that they discovered NA improved effects in the depression-like behavior of rats by three validated assays—the sucrose preference test, open-field test, and forced swim test. Poststroke depression (PSD)-like behavior presents a difficult clinical challenge, serving as a critical complication of stroke with great implications for patient disability and mortality. Previous studies have reported that PSD affects between 11% to 41% of stroke survivors within two years[31].

Firstly, direct supplementation of NA in the brain was observed. And, because NA is administered by gavage, they hypothesized that its beneficial effects on PSD symptoms arise from its metabolism and interactions with gut microbiota. They found an increase in the abundance of Blautia and Sutterella, which participated in phenylalanine metabolism. At the same time, the metabolomics of plasma and brain samples revealed a decrease in the levels of phenylalanine-based amino acids, which alleviated the inhibitory effects on glutamine metabolism and promoted the recovery and signaling transmission of neurons after stroke. Altogether, their findings suggest that NA can be a viable treatment option for alleviating stroke and its associated poststroke depressive-like behaviors.

This study is led by Dr. Yong Fan (Qingdao Institute of Bioenergy and Bioprocess Technology, the Chinese Academy of Sciences) and Prof. Xianyu Li (China Academy of Chinese Medical Sciences).

See the article:

Nervonic acid can alleviate stroke and its associated poststroke depression behaviors

https://doi.org/10.1016/j.hlife.2024.08.001