Astroglial water channel aquaporin 4-mediated glymphatic clearance function: A determined factor for time-sensitive treatment of aerobic exercise in patients with Alzheimer’s disease

Yin, Mengmei; Pu, Tinglin; Wang, Linmei; Marshall, Charles; Wu, Ting; Xiao, Ming

doi:10.1016/j.mehy.2018.07.016

Cited by 16 publications

(15 citation statements)

References 41 publications

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“…The meta-analysis identified the anesthesia protocol, wide age range of the experimental animals and the injection paradigm are potential causes for the conflicting data reported by Smith et al However, it is important to note that glymphatic transport is affected by multiple pathways other than AQP4. For example, the sleep-wake cycle (Xie et al, 2013), brain injury in the setting of trauma or ischemia (Iliff et al, 2014; Wang et al, 2017), exercise (He et al, 2017; von Holstein-Rathlou et al, 2018; Yin et al, 2018), amyloid-β accumulation and acute amyloid-β toxicity (Xu et al, 2015; Peng et al, 2016), omega-3 fatty acids (Ren et al, 2017), plasma osmolarity (Plog et al, 2018), and aging (Kress et al, 2014) are important regulators of glymphatic transport. How AQP4 on a cellular level facilitates CSF-ISF exchange remains to be firmly established.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-4-dependent glymphatic solute transport in the rodent brain

Mestre

Hablitz

Xavier

et al. 2018

eLife

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The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-β. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.

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Section: Discussionmentioning

confidence: 99%

Aquaporin-4-dependent glymphatic solute transport in the rodent brain

Mestre

Hablitz

Xavier

et al. 2018

eLife

Self Cite

444

437

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“…Our recent study has revealed that brain Aβ and Tau levels are markedly increased in AQP4 -/- mice following ligation of dcLNs [32]. These data indicate that inhibiting mislocalization of astrocyte AQP4 might be an effective treatment target to protect glymphatic function in various neurological diseases associated with abnormal aggregation of brain macromolecules [33].…”

Section: Discussionmentioning

confidence: 99%

Persistent Malfunction of Glymphatic and Meningeal Lymphatic Drainage in a Mouse Model of Subarachnoid Hemorrhage

Zou

Feng

et al. 2019

Exp Neurobiol

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Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event that often is followed by permanent brain impairments. It is necessary to explore the pathogenesis of secondary pathological damages in order to find effective interventions for improving the prognosis of SAH. Blockage of brain lymphatic drainage has been shown to worsen cerebral ischemia and edema after acute SAH. However, whether or not there is persistent dysfunction of cerebral lymphatic drainage following SAH remains unclear. In this study, autologous blood was injected into the cisterna magna of mice to establish SAH model. One week after surgery, SAH mice showed decreases in fluorescent tracer drainage to the deep cervical lymph nodes (dcLNs) and influx into the brain parenchyma after injection into the cisterna magna. Moreover, SAH impaired polarization of astrocyte aquaporin-4 (AQP4) that is a functional marker of glymphatic clearance and resulted in accumulations of Tau proteins as well as CD3 + , CD4 + , and CD8 + cells in the brain. In addition, pathological changes, including microvascular spasm, activation of glial cells, neuroinflammation, and neuronal apoptosis were observed in the hippocampus of SAH mice. Present results demonstrate persistent malfunction of glymphatic and meningeal lymphatic drainage and related neuropathological damages after SAH. Targeting improvement of brain lymphatic clearance potentially serves as a new strategy for the treatment of SAH.

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“…2 Aquaporin 4 (AQP4), a principal water channel protein, is exclusively expressed by astrocytes, and mediates CNS water homeostasis, glymphatic system function, synaptic plasticity, and cognitive function. 48,49 Aqp4 is strongly expressed on the side of astrocytes that connects with pericytes. 50 Pericyte deficiency results in a redistribution of AQP4 on astrocyte end-feet where AQP4 moves away and is expressed on other side of astrocytes with no vessel contact.…”

Section: Pericyte Effects In Cell–cell Interactionsmentioning

confidence: 99%

“…86 In the glymphatic system, CSF enters the paravascular spaces around penetrating vessels, travels along the downstream arteries, reaches the basal lamina surrounding capillaries, continues along the paravenous routes, and finds its drainage outlet via cervical lymphatics. 48 Along this brain-throughout journey, AQP4 on end-feet is important for the mediation of CSF clearance. 48 As noted above, pericytes regulate AQP4 distribution of astrocytes end-feet.…”

Section: Physiological Roles Of Pericytes In the Cnsmentioning

confidence: 99%

Multifaceted roles of pericytes in central nervous system homeostasis and disease

Zheng

Chopp

Chen

2020

J Cereb Blood Flow Metab

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Pericytes, the mural cells surrounding microcirculation, are gaining increasing attention for their roles in health and disease of the central nervous system (CNS). As an essential part of the neurovascular unit (NVU), pericytes are actively engaged in interactions with neighboring cells and work in synergy with them to maintain homeostasis of the CNS, such as maintaining the blood–brain barrier (BBB), regulating cerebral blood flow (CBF) and the glymphatic system as well as mediating immune responses. However, the dysfunction of pericytes may contribute to the progression of various pathologies. In this review, we discuss: (1) origin of pericytes and different pericyte markers; (2) interactions of pericytes with endothelial cells (ECs), astrocytes, microglia, oligodendrocytes, and neurons; (3) physiological roles of pericytes in the CNS; (4) effects of pericytes in different CNS diseases; (5) relationship of pericytes with extracellular vesicles (EVs) and microRNAs (miRs); (6) recent advances in pericytes studies and future perspective.

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Astroglial water channel aquaporin 4-mediated glymphatic clearance function: A determined factor for time-sensitive treatment of aerobic exercise in patients with Alzheimer’s disease

Cited by 16 publications

References 41 publications

Aquaporin-4-dependent glymphatic solute transport in the rodent brain

Aquaporin-4-dependent glymphatic solute transport in the rodent brain

Persistent Malfunction of Glymphatic and Meningeal Lymphatic Drainage in a Mouse Model of Subarachnoid Hemorrhage

Multifaceted roles of pericytes in central nervous system homeostasis and disease

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