Altered clearance of beta-amyloid from the cerebrospinal fluid following subchronic lead exposure in rats: Roles of RAGE and LRP1 in the choroid plexus

Shen, Xiaoli; Xia, Li; Liu, Luqing; Jiang, Hong; Shannahan, Jonathan H.; Du, Yansheng; Zheng, Wei

doi:10.1016/j.jtemb.2020.126520

Cited by 20 publications

(20 citation statements)

References 36 publications

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“…Therefore, we investigated the deposition of Aβ 1-40 in choroid plexus and microvessels following lead exposure and we observed that lead treatment significantly promoted the deposition of Aβ1-40 in these two vascularized structures in the brain. In line with our study, recently, Shen et al reported that the expression of Aβ in the choroid plexus was significantly upregulated in leadtreated group [31]. Furthermore, the expression of ABCB1, LRP-1, and RAGE, three major receptors responsible for Aβ transportation, was measured.…”

Section: Discussionsupporting

confidence: 91%

Lead Exposure in Developmental Ages Promotes Aβ Accumulation by Disturbing Aβ Transportation in Blood-Cerebrospinal Fluid Barrier/Blood–Brain Barriers and Impairing Aβ Clearance in the Liver

Zhou

Wang

et al. 2021

Biol Trace Elem Res

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Environmental lead exposure is closely related to the progression of Alzheimer's disease (AD). Our previous study has shown that exposure to lead could result in the cholesterol unbalance and increase amyloid-beta (Aβ) generation in the brain. However, the potential effect of lead exposure on Aβ transportation is poorly reported. In this study, we sought to explore whether lead exposure in developmental ages impaired the integrity of BCSFB and BBB, two highly vascularized structures in the brain in a rat model. The Aβ clearance in the liver was also assessed. Our results showed that lead treatment in developmental ages increased the number of TUNEL-positive apoptotic cells in rat choroid plexus and microvessels. Moreover, lead exposure markedly increased pro-inflammatory factors expression including TNF-α and IL-1β in rat choroid plexus and microvessels. Interestingly, lead treatment increased the expression of AQP-1 and reduced the expression of TTR, two key proteins associated with the functions of choroid plexus and microvessels. Additionally, the expressions of ABCB1, LRP-1, and RAGE, three major receptors responsible for Aβ transportation, were disturbed by developmental lead exposure. All these pathologies resulted in Aβ 1-40 deposition within BCSFB and BBB and malfunctions of these two vascularized structures. Finally, we found that lead treatment remarkably inhibited the gene expression of LRP-1, which is responsible for Aβ endocytosis, in the liver tissue of the rat model. Collectively, our results provide the first evidence that developmental lead exposure induces Aβ deposition in BCSFB and BBB and impairs Aβ clearance in the liver, which would ultimately disturb Aβ transportation via choroid plexus/brain microvessels and facilitate Aβ deposition in the brain.

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Section: Discussionsupporting

confidence: 91%

Lead Exposure in Developmental Ages Promotes Aβ Accumulation by Disturbing Aβ Transportation in Blood-Cerebrospinal Fluid Barrier/Blood–Brain Barriers and Impairing Aβ Clearance in the Liver

Zhou

Wang

et al. 2021

Biol Trace Elem Res

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“…A longitudinal incision was made in the scalp to expose the surface of the skull. A cranial burr hole (1 mm) was drilled into the skull of the right hemisphere with the following coordinates: 0.3 mm posterior to bregma and 1.0 mm lateral to the midline ( Paxinos and Franklin, 2001 ; Shen et al, 2017 , 2020 ). Next, a stainless steel cannula (RWD, Shenzhen, China) was embedded at 3.2 mm vertical from the skull surface ( Young et al, 2012 ).…”

Section: Methodsmentioning

confidence: 99%

“…ICV injection of drug solutions was performed manually at a rate of 0.5 μL/min ( Dore et al, 2017 ) in freely moving animals through the cannula, which was connected to a 5 μL Hamilton microsyringe (Reno, NV, United States), and the injection cannula was kept in situ for an additional 3 min to avoid reflux of the solution along the injector track. The ICV injection technique is well established in this lab and was used in our previous studies ( Shen et al, 2017 , 2020 ).…”

Section: Methodsmentioning

confidence: 99%

“…Cerebrospinal fluid samples from six mice per group were collected for ELISA. CSF samples (10 μL) were diluted 1:20 with artificial CSF (a buffer containing 103 mmol/L NaCl, 4.7 mmol/L KCl, 1.2 mmol/L KH2PO4, 1.2 mmol/L MgSO4, 25 mmol/L NaHCO3, 10 mmol/L glucose, 1 mmol/L sodium pyruvate, and 2.5 mmol/L CaCl2, pH 7.4) ( Shen et al, 2020 ). Concentrations of nesfatin-1 in the CSF were determined by a mouse nesfatin-1 ELISA kit from JianglaiBIO (Beijing, China) according to the manufacturer’s instructions ( Zhang et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

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Reduction in Nesfatin-1 Levels in the Cerebrospinal Fluid and Increased Nigrostriatal Degeneration Following Ventricular Administration of Anti-nesfatin-1 Antibody in Mice

Chen

et al. 2021

Front. Neurosci.

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Nesfatin-1 is one of several brain-gut peptides that have a close relationship with the central dopaminergic system. Our previous studies have shown that nesfatin-1 is capable of protecting nigral dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. A recent study also revealed a reduced blood level of nesfatin-1 in patients with Parkinson’s disease (PD). The current study was designed to investigate whether reduced nesfatin-1 in cerebrospinal fluid (CSF) induces nigrostriatal system degeneration. An intra-cerebroventricular (ICV) injection technique was used to administer anti-nesfatin-1 antibody directly into the lateral ventricle of the brain. Enzyme-linked immunosorbent assay (ELISA) results showed that ICV injection of anti-nesfatin-1 antibody into the lateral ventricle of the brain once daily for 2 weeks caused a significant reduction in nesfatin-1 levels in the CSF (93.1%). Treatment with anti-nesfatin-1 antibody resulted in a substantial loss (23%) of TH-positive (TH+) dopaminergic neurons in the substantia nigra pars compacta (SNpc), as shown by immunofluorescence staining, a depletion in dopamine and its metabolites in the striatum detected by high-performance liquid chromatography (HPLC), and obvious nuclear shrinkage and mitochondrial lesions in dopaminergic neurons in the SNpc detected by transmission electron microscopy (TEM). Furthermore, the results from our Western blot and ELISA experiments demonstrated that anti-nesfatin-1 antibody injection induced an upregulation of caspase-3 activation, increased the expression of p-ERK, and elevated brain-derived neurotrophic factor (BDNF) levels in the SNpc. Taken together, these observations suggest that reduced nesfatin-1 in the brain may induce nigrostriatal dopaminergic system degeneration; this effect may be mediated via mitochondrial dysfunction-related apoptosis. Our data support a role of nesfatin-1 in maintaining the normal physiological function of the nigrostriatal dopaminergic system.

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“…The complex equilibrium between fluid drainage and Aβ deposition observed at the perivascular level in AD is also detected within the ChP. Aβ transporter proteins are expressed at both the BBB and BCSFB contributing to a coordinated clearance of Aβ into the peripheral circulation ( 123 , 360 , 361 ). Underscoring disease-specific defects in barrier transport mechanisms, ChP tissue from AD patients shows substantial deposition of Aβ peptide and increased oxidative stress ( 362 ).…”

Section: Myeloid Dwellers and Trespassers At Cns Interfaces In Neurodmentioning

confidence: 99%

Dwellers and Trespassers: Mononuclear Phagocytes at the Borders of the Central Nervous System

et al. 2021

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The central nervous system (CNS) parenchyma is enclosed and protected by a multilayered system of cellular and acellular barriers, functionally separating glia and neurons from peripheral circulation and blood-borne immune cells. Populating these borders as dynamic observers, CNS-resident macrophages contribute to organ homeostasis. Upon autoimmune, traumatic or neurodegenerative inflammation, these phagocytes start playing additional roles as immune regulators contributing to disease evolution. At the same time, pathological CNS conditions drive the migration and recruitment of blood-borne monocyte-derived cells across distinct local gateways. This invasion process drastically increases border complexity and can lead to parenchymal infiltration of blood-borne phagocytes playing a direct role both in damage and in tissue repair. While recent studies and technical advancements have highlighted the extreme heterogeneity of these resident and CNS-invading cells, both the compartment-specific mechanism of invasion and the functional specification of intruding and resident cells remain unclear. This review illustrates the complexity of mononuclear phagocytes at CNS interfaces, indicating how further studies of CNS border dynamics are crucially needed to shed light on local and systemic regulation of CNS functions and dysfunctions.

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Altered clearance of beta-amyloid from the cerebrospinal fluid following subchronic lead exposure in rats: Roles of RAGE and LRP1 in the choroid plexus

Cited by 20 publications

References 36 publications

Lead Exposure in Developmental Ages Promotes Aβ Accumulation by Disturbing Aβ Transportation in Blood-Cerebrospinal Fluid Barrier/Blood–Brain Barriers and Impairing Aβ Clearance in the Liver

Lead Exposure in Developmental Ages Promotes Aβ Accumulation by Disturbing Aβ Transportation in Blood-Cerebrospinal Fluid Barrier/Blood–Brain Barriers and Impairing Aβ Clearance in the Liver

Reduction in Nesfatin-1 Levels in the Cerebrospinal Fluid and Increased Nigrostriatal Degeneration Following Ventricular Administration of Anti-nesfatin-1 Antibody in Mice

Dwellers and Trespassers: Mononuclear Phagocytes at the Borders of the Central Nervous System

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