Age-dependent decline of copper clearance at the blood-cerebrospinal fluid barrier

Liu, Luke L.; Du, David Hung-Chang; Zheng, Wei; Zhang, Yanshu

doi:10.1016/j.neuro.2021.10.011

Cited by 7 publications

(6 citation statements)

References 52 publications

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“…A recent study reported that the aging process diminished copper clearance from the CSF of rats by disrupting copper transporting proteins in the choroid plexus. 10 In the present study, no significant difference was found for median CSF concentrations of target analytes between genders ( Table 2 ).…”

Section: Resultscontrasting

confidence: 54%

Detection of Neonicotinoid Insecticides and Their Metabolites in Human Cerebrospinal Fluid

Yin

et al. 2022

Environ Health Perspect

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Section: Resultscontrasting

confidence: 54%

Detection of Neonicotinoid Insecticides and Their Metabolites in Human Cerebrospinal Fluid

Yin

et al. 2022

Environ Health Perspect

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“…Following Pb exposure for 4 or 8 weeks, in situ brain perfusion was conducted to investigate how Pb exposure affected the Aβ 40 affinity to cerebral capillaries and brain parenchyma. This technique has been routinely used by this laboratory for studies such as trace element metal copper (Cu) and Aβ peptide uptake by BBB and blood-CSF barrier (BCB) [ 14 , 31 , 52 ]. Briefly, 24 h after last gavage, rats were anesthetized by ketamine/xylazine (75:10 mg/kg, ip) and placed on a heating pad in a supine position.…”

Section: Methodsmentioning

confidence: 99%

“…WB assay was performed as previously described [ 31 ]. Briefly, the extracted protein samples from brain regional capillaries and parenchyma were diluted with sample buffer to the final protein concentrations of appropriately 2 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

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High affinity of β-amyloid proteins to cerebral capillaries: implications in chronic lead exposure-induced neurotoxicity in rats

Liu

Shen

et al. 2023

Fluids Barriers CNS

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Lead (Pb) is a known environmental risk factor in the etiology of Alzheimer’s disease (AD). The existing reports suggest that Pb exposure increases beta-amyloid (Aβ) levels in brain tissues and cerebrospinal fluid (CSF) and facilitates the formation of amyloid plaques, which is a pathological hallmark for AD. Pb exposure has long been associated with cerebral vasculature injury. Yet it remained unclear if Pb exposure caused excessive Ab buildup in cerebral vasculature, which may damage the blood–brain barrier and cause abnormal Ab accumulation. This study was designed to investigate the impact of chronic Pb exposure on Aβ accumulation in cerebral capillary and the expression of low-density lipoprotein receptor protein-1 (LRP1), a critical Aβ transporter, in brain capillary and parenchyma. Sprague–Dawley rats received daily oral gavage at doses of 0, 14 (low-dose), and 27 (high-dose) mg Pb/kg as Pb acetate, 5 d/wk, for 4 or 8 wks. At the end of Pb exposure, a solution containing Aβ40 was infused into the brain via the cannulated internal carotid artery. Data by ELISA showed a strikingly high affinity of Ab to cerebral vasculature, which was approximately 7–14 times higher than that to the parenchymal fractions collected from control brains. Pb exposure further aggravated the Aβ accumulation in cerebral vasculature in a dose-dependent manner. Western blot analyses revealed that Pb exposure decreased LRP1 expression in cortical capillaries and hippocampal parenchyma. Immunohistochemistry (IHC) studies further revealed a disrupted distribution of LRP1 alongside hippocampal vasculature accompanied with a decreased expression in hippocampal neurons by Pb exposure. Taken together, the current study demonstrated that the cerebral vasculature naturally possessed a high affinity to Aβ present in circulating blood. Pb exposure significantly increased Aβ accumulation in cerebral vasculature; such an increased Aβ accumulation was due partly to the diminished expression of LRP1 in response to Pb in tested brain regions. Perceivably, Pb-facilitated Ab aggravation in cerebral vasculature may contribute to Pb-associated amyloid alterations.

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“…Western blot was performed as previously described (Liu et al 2022a). Briefly, proteins were extracted from samples with RIPA buffer supplemented with protease inhibitor.…”

Section: Western Blotmentioning

confidence: 99%

Choroid Plexus Modulates Subventricular Zone Adult Neurogenesis and Olfaction Through Secretion of Small Extracellular Vesicles

Liu

Shannahan

Zheng

2023

Preprint

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The choroid plexus (CP) in brain ventricles secrete cerebrospinal fluid (CSF) that bathes the adjacent subventricular zone (SVZ); the latter is the largest neurogenic region in adult brain harboring neural stem/progenitor cells (NSPCs) and supplies newborn neurons to the olfactory bulb (OB) for normal olfaction. We discovered the presence of a CP-SVZ regulatory (CSR) axis in which the CP, by secreting small extracellular vesicles (sEVs), regulated adult neurogenesis in the SVZ and maintained olfaction. The proposed CSR axis was supported by 1) differential neurogenesis outcomes in the OB when animals treated with intracerebroventricular (ICV) infusion of sEVs collected from the CP of normal or manganese (Mn)-poisoned mice, 2) progressively diminished SVZ adult neurogenesis in mice following CP-targeted knockdown of SMPD3 to suppress CP sEV secretion, and 3) compromised olfactory performance in these CP-SMPD3-knockdown mice. Collectively, our findings demonstrate the biological and physiological presence of this sEV-dependent CSR axis in adult brains.

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Age-dependent decline of copper clearance at the blood-cerebrospinal fluid barrier

Cited by 7 publications

References 52 publications

Detection of Neonicotinoid Insecticides and Their Metabolites in Human Cerebrospinal Fluid

Detection of Neonicotinoid Insecticides and Their Metabolites in Human Cerebrospinal Fluid

High affinity of β-amyloid proteins to cerebral capillaries: implications in chronic lead exposure-induced neurotoxicity in rats

Choroid Plexus Modulates Subventricular Zone Adult Neurogenesis and Olfaction Through Secretion of Small Extracellular Vesicles

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