Abstract
BackgroundAccumulating evidence suggests that a decrease in brain-derived neurotrophic factor (BDNF) level induces a variety of psychiatric and neurological disorders. However, the expression and role of BDNF in the kidney have not been explored. The present study examined the expression of BDNF and tropomyosin-related kinase (Trk) receptors in an experimental model of chronic cyclosporine A (CsA) nephropathy.MethodsSprague-Dawley rats on a salt-deplete diet were treated daily for four weeks with vehicle or CsA. Urine profiles, apoptotic cell death, oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-OHdG), and expression of BDNF and Trk receptors (TrkB and TrkC) were compared between groups. The impact of vasopressin infusion on the urine-concentrating ability was examined by measuring the expression of aquaporin-2 (AQP-2) and BDNF and urine profiles in normal and CsA-treated rats.ResultsCompared with the vehicle-treated rats, rats given CsA had enhanced urine volume and declined urine osmolality. Immunohistochemistry and immunoblotting showed that BDNF and Trk receptors were constitutively expressed in kidneys from vehicle-treated rats. This was confirmed by double immunofluorescent staining for Na-K-ATPase-α1, AQP-1, and AQP-2. By contrast, the expression of these factors decreased in kidneys from CsA-treated rats (BDNF: 51.1 ± 19.5% vs. 102.0 ± 30.3%, p < 0.01). Downregulation of BDNF was accompanied by impairment of urine osmolality, and this was reversed by exogenous infusion of vasopressin. Notably, the number of TUNEL-positive cells correlated negatively with BDNF expression and positively with urinary 8-OHdG excretion.ConclusionsBDNF is expressed in the collecting duct of the kidney and may be associated with urine-concentrating ability in an experimental model of chronic CsA-induced nephropathy. Our study provides a new avenue for further investigation of chronic CsA nephropathy.
Highlights
Accumulating evidence suggests that a decrease in brain-derived neurotrophic factor (BDNF) level induces a variety of psychiatric and neurological disorders
Immunoblotting revealed that BDNF expression was about 50% lower after cyclosporine A (CsA) treatment compared with VH treatment (Fig. 3; 51.1 ± 19.5% vs. 102.0 ± 30.3%, p < 0.05)
The present study clearly demonstrates that BDNF and tropomyosin-related kinase (Trk) receptors (TrkB and TrkC) are constitutively expressed in the collecting duct of normal rat kidneys, whereas the expression is significantly lower in the kidneys of CsA-treated rats
Summary
Accumulating evidence suggests that a decrease in brain-derived neurotrophic factor (BDNF) level induces a variety of psychiatric and neurological disorders. The expression and role of BDNF in the kidney have not been explored. The present study examined the expression of BDNF and tropomyosin-related kinase (Trk) receptors in an experimental model of chronic cyclosporine A (CsA) nephropathy. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin superfamily which promotes the proliferation, development, survival, and differentiation of neurons in the peripheral and central nervous systems [1]. Mature BDNF binds to the tropomyosin-related kinase receptor B (tyrosine kinase B, TrkB) and thereby initiates phosphorylation through the mitogen-activated protein kinases, phosphatidylinositol 3-kinase, and phospholipase C-gamma signaling pathways, which accelerate protein synthesis, axonal growth, dendritic cell maturation, synaptic plasticity, and neuroprotective effect. Low BDNF level or impairment of its signaling pathway is thought to be implicated in a variety of neuropsychiatric and neurological disorders. The role and expression of BDNF in the kidney remains underexplored
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