Polyunsaturated fatty acid supplement alleviates depression-incident cognitive dysfunction by protecting the cerebrovascular and glymphatic systems

Liu, Xinghua; Hao, Jiahuan; Yao, Ensheng; Cao, Jie; Zheng, Xiaolong; Yao, Di; Zhang, Chenyan; Li, Jia; Pan, Dengji; Luo, Xiang; Wang, Minghuan; Wang, Wei

doi:10.1016/j.bbi.2020.07.022

Cited by 58 publications

(61 citation statements)

References 46 publications

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“…The control of CSF flow may impact the neurological, neurodegenerative, and psychiatric diseases through the integrated action of the ependymal cell milieu, including CSF and blood vessels, glymphatic system, supraependymal serotonergic, cholinergic and dopaminergic axons, and neural circuits [ 14 , 19 , 21 , 22 ]. In addition, CSF flow is regulated by respiration [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…The CSF flow, which is initiated at the lateral ventricle (LV), maintains CSF homeostasis, and guides neuroblast migration and neurogenesis [14,19,20]. The CSF dynamic is highly organized with the glymphatic system for the perivascular exchange of CSF and interstitial fluid (ISF) [21,22]. Aging and neurological, neurodegenerative, and psychiatric disorders in humans have been associated with abnormal CSF flow [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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Ependymal cells-CSF flow regulates stress-induced depression

et al. 2021

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Major depressive disorder (MDD) is a severe, common mood disorder. While reduced cerebrospinal fluid (CSF) flow adversely affects brain metabolism and fluid balance in the aging population and during development, only indirect evidence links aberrant CSF circulation with many diseases including neurological, neurodegenerative, and psychiatric disorders, such as anxiety and depression. Here we show a very high concentration of p11 as a key molecular determinant for depression in ependymal cells, which is significantly decreased in patients with MDD, and in two mouse models of depression induced by chronic stress, such as restraint and social isolation. The loss of p11 in ependymal cells causes disoriented ependymal planar cell polarity (PCP), reduced CSF flow, and depression-like and anxiety-like behaviors. p11 intrinsically controls PCP core genes, which mediates CSF flow. Viral expression of p11 in ependymal cells specifically rescues the pathophysiological and behavioral deficits caused by loss of p11. Taken together, our results identify a new role and a key molecular determinant for ependymal cell-driven CSF flow in mood disorders and suggest a novel strategy for development of treatments for stress-associated neurological, neurodegenerative, and psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ependymal cells-CSF flow regulates stress-induced depression

et al. 2021

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“…This study used the CUMS rat model of depression (Liu et al 2020). Feed and drinking water were supplied ad libitum before the experiment, and 1% sucrose water training was conducted before the experiment 24 hours.…”

Section: Rat Model Of Cumsmentioning

confidence: 99%

Jiaotai Wan exerts antidepressant effects through regulating gut microbiota in rat model of chronic unpredictable mild stress

Wang¹,

Z²,

Feng³

et al. 2021

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This study used 16S rDNA high-throughput sequencing to determine the effects of Jiaotai Wan on gut microflora of rats experiencing chronic unpredictable mild stress. We randomly divided 135 healthy male rats into nine groups. All groups except the control received chronic unpredictable mild stress. Rats were weighed before being subjected to sucrose preference and open field tests. Rat fecal samples were used for 16s rDNA high-throughput sequencing; the results allowed us to determine gut microfloral structure and changes. The stress treatment decreased body weight, sucrose preference, and performance in open field tests from control levels. Beta diversity of gut microflora differed across rat groups. Jiaotai Wan increased Lachnospiraceae, Bacteroides, and Akkermansia abundance, while decreasing Ruminococcaceae abundance. Therefore, Jiaotai Wan may exert antidepressant effects through regulating microbial abundance in the gut.

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“…The regulation of fluid homeostasis in the brain is achieved through the glymphatic system. The glymphatic system refers to the drainage pathways through which metabolic waste products and other undesirable components get flushed out of the brain, thereby stabilizing microenvironmental homeostasis and providing suitable working conditions for the brain parenchymal cells ( 9 , 10 ). The system relies on the bulk flow of cerebrospinal fluid (CSF) produced by the choroid plexus.…”

Section: Introductionmentioning

confidence: 99%

“…Presently, the role that the glymphatic system plays in cART-treated HIV individuals is poorly known. Previous studies have documented the mechanisms of the glymphatic system and its roles in most neurodegenerative diseases ( 10 , 13 ). An impairment in the glymphatic clearance function has been shown to accelerate the accumulation of abluminal protein deposits, α-synuclein, Aβ and tau, and huntingtin, which, respectively, underpin small vessel disease, Parkinson's disease, Alzheimer's disease (AD), and Huntington's disease ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Altered Glymphatic System in Middle-Aged cART-Treated Patients With HIV: A Diffusion Tensor Imaging Study

et al. 2022

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Objective:The brain relies on the glymphatic system to clear metabolic wastes and maintain brain homeostasis to fulfill its functions better. Yet, the complexity of the glymphatic flow and clearance and its changes in HIV infection and its role in neurocognitive dysfunction remain poorly understood. This study aims to explore the impact of HIV and combination antiretroviral therapy (cART) on the glymphatic system and establish a potential biomarker of HIV-associated neurocognitive disorders (HAND).MethodsHere, we examined the glymphatic profiles of middle-aged virosuppressed patients with HIV (n = 27) receiving cART over 1–6 years and healthy controls (n = 28) along the perivascular space (PVS) using diffusion tensor image analysis along the perivascular space (ALPS) with guided and unguided approaches. We later combined data from these analyses to investigate MRI glymphatic correlates of cognitive impairment and other clinical tests of HIV (CD4+ T-cell counts and CD4+/CD8+ ratio).ResultsWe found that glymphatic function as measured by the ALPS index increased significantly in the right and left PVSs of patients with HIV having cART. On antiretroviral therapy, a changing pattern in glymphatic clearance function in patients with HIV having cART correlated with attention and working memory. Duration on cART was also associated with cognitive performances of abstract and executive function and learning and memory.ConclusionThese findings provide MRI evidence of the presence of HIV-induced changes in the glymphatic flow and clearance, which might underlie cognitive impairment among patients with HIV having cART. An increase in the glymphatic activity might reflect a compensatory mechanism to regulate microenvironment homeostasis compromised by HIV. This compensation might be necessary to maintain the proper functioning of the brain while coping with HIV pathology. These findings also shed light on the clinical importance of evaluating glymphatic function based on the ALPS index and suggest that improving the glymphatic system may serve as an alternative therapeutic strategy for HAND.

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Polyunsaturated fatty acid supplement alleviates depression-incident cognitive dysfunction by protecting the cerebrovascular and glymphatic systems

Cited by 58 publications

References 46 publications

Ependymal cells-CSF flow regulates stress-induced depression

Ependymal cells-CSF flow regulates stress-induced depression

Jiaotai Wan exerts antidepressant effects through regulating gut microbiota in rat model of chronic unpredictable mild stress

Altered Glymphatic System in Middle-Aged cART-Treated Patients With HIV: A Diffusion Tensor Imaging Study

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