A highly reproducible mice model of chronic kidney disease: Evidences of behavioural abnormalities and blood-brain barrier disruption

Mazumder, Muhammed Khairujjaman; Giri, Anirudha; Kumar, Sanjeev; Borah, Anupom

doi:10.1016/j.lfs.2016.07.020

Cited by 50 publications

(46 citation statements)

References 65 publications

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“…Mice with CKD induced by adenine feeding for four weeks presented higher serum concentrations of urea nitrogen. In this model, authors observed significant blood–brain barrier disruption and behavioral abnormalities (Mazumder et al, 2016). Blood–brain barrier disruption was also found in nephrectomized rats with chronic uremia and was linked to uremic encephalopathy (Jeppsson et al, 1982).…”

Section: Discussionmentioning

confidence: 97%

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

Kałaska

Pawlak

Oksztulska-Kolanek

et al. 2017

PeerJ

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BackgroundDisturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD.MethodsThirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites.ResultsSubtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry.DiscussionIn addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD.

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Section: Discussionmentioning

confidence: 97%

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

Kałaska

Pawlak

Oksztulska-Kolanek

et al. 2017

PeerJ

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“…As a high adenine diet is known to induce CKD in mice via the development of tubulointerstitial nephropathy [26][27][28]30], we first fed mice with a 0.25% adenine-enriched diet for 2 weeks, and then with a normal diet for 1 week. We observed a 100% mortality rate of AhR −/− males, whereas the mortality of WT mice was 27%, which was also a relatively high rate.…”

Section: Discussionmentioning

confidence: 99%

“…In the early 1980s, Yokozawa et al induced CKD in rat with dietary adenine [25]. More recently, a high-adenine diet was shown to induce CKD in mice via the development of tubulointerstitial nephropathy [26][27][28]. In excess, adenine becomes a significant substrate for xanthine dehydrogenase (XDH), which oxidizes adenine into 2,8-dihydroxyadenine (DHA).…”

Section: Introductionmentioning

confidence: 99%

Female AhR Knockout Mice Develop a Minor Renal Insufficiency in an Adenine-Diet Model of Chronic Kidney Disease

Makhloufi

Nicolas

McKay

et al. 2020

IJMS

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Cardiovascular complications observed in chronic kidney disease (CKD) are associated with aryl hydrocarbon receptor (AhR) activation by tryptophan-derived uremic toxins—mainly indoxyl sulfate (IS). AhR is a ligand-activated transcription factor originally characterized as a receptor of xenobiotics involved in detoxification. The aim of this study was to determine the role of AhR in a CKD mouse model based on an adenine diet. Wild-type (WT) and AhR−/− mice were fed by alternating an adenine-enriched diet and a regular diet for 6 weeks. Our results showed an increased mortality rate of AhR−/− males. AhR−/− females survived and developed a less severe renal insufficiency that WT mice, reflected by urea, creatinine, and IS measurement in serum. The protective effect was related to a decrease of pro-inflammatory and pro-fibrotic gene expression, an attenuation of tubular injury, and a decrease of 2,8-dihydroxyadenine crystal deposition in the kidneys of AhR−/− mice. These mice expressed low levels of xanthine dehydrogenase, which oxidizes adenine into 2,8-dihydroxyadenine, and low levels of the IS metabolism enzymes. In conclusion, the CKD model of adenine diet is not suitable for AhR knockout mice when studying the role of this transcription factor in cardiovascular complications, as observed in human CKD.

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“…Cerebral ROS levels increased 144% on day three PI [t(10) = 3.99; (Mairey et al, 2006), which contribute to disease pathogenesis and appearance of neurological disorders. Several studies have associated BBB breakdown with behavioural abnormalities, such as depressive-like and anxiolytic behaviour (Mazumder, Giri, Kumar, & Borah, 2016), cognitive dysfunction (Zhang et al, 2016) and motor behavioural abnormalities in mice (Mazumder et al, 2016;Yang, Huang, & Cheng, 2016). In this sense, a recent study conducted by Baldissera et al (2017) To clarify the action mechanisms involved in the BBB breakdown during Pseudomonas aeruginosa infection, we decided to evaluate two mechanisms linked with BBB disruption during bacterial infections: the cerebral MPO activity and the cerebral ROS levels.…”

Section: Cerebral Reactive Oxygen Species Levelsmentioning

confidence: 99%

Blood–brain barrier breakdown and myeloperoxidase activity in silver catfish experimentally infected with Pseudomonas aeruginosa

Baldissera

Souza

Santos

et al. 2017

Journal of Fish Diseases

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Central nervous system (CNS) infections continue to be an important cause of morbidity and mortality, and microbial invasion of the blood-brain barrier (BBB) is considered a prerequisite for CNS infections, which contribute to behavioural abnormalities and disease pathogenesis. Based on this information, the aim of this study was to evaluate whether Pseudomonas aeruginosa causes disruption of the BBB, and to investigate the involvement of cerebral myeloperoxidase (MPO) activity in this process in experimentally infected silver catfish. The permeability of the BBB to Evans blue dye increased in the infected animals on days three and six post-infection (PI) compared to the control group. Moreover, cerebral MPO activity and reactive oxygen species (ROS) levels also increased in the infected animals on days three and six PI compared to the control group. Based on this evidence, we concluded that P. aaeruginosa causes a disruption of the BBB, which may contribute to disease pathogenesis in the CNS. Moreover, the increase in cerebral MPO activity and ROS levels may be considered a pathway involved in BBB breakdown, allowing the passage of bacteria to the CNS.

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A highly reproducible mice model of chronic kidney disease: Evidences of behavioural abnormalities and blood-brain barrier disruption

Cited by 50 publications

References 65 publications

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

Female AhR Knockout Mice Develop a Minor Renal Insufficiency in an Adenine-Diet Model of Chronic Kidney Disease

Blood–brain barrier breakdown and myeloperoxidase activity in silver catfish experimentally infected with Pseudomonas aeruginosa

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