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Published on: May 22, 2019
Persistent changes within the intrinsic kidney-associated NPY system and tubular function by litter size reduction
Miguel Angel Alejandre Alcázar1, Eva Boehler, Kerstin Amann
1Department of Pediatric and Adolescent Medicine, University of Cologne, Cologne, Germany. miguel.alejandre-alcazar@uk-koeln.de
Insights
Early life stress and nutrition impact kidney function by altering Neuropeptide Y (NPY) signaling. Reduced litter size in rats impaired renal function, highlighting the role of postnatal environment in kidney health.
Area of Science:
- Nephrology
- Developmental Biology
- Endocrinology
Background:
- Intrauterine growth restriction (IUGR) increases adult renal disease risk.
- Postnatal factors like nutrition and stress impact kidney development, but their effects on Neuropeptide Y (NPY) signaling are unclear.
- NPY regulates blood pressure and tubular function, but its role in the kidney's response to early life events is not well understood.
Purpose of the Study:
- To investigate the impact of early postnatal environmental factors on renal Neuropeptide Y (NPY) expression and function.
- To determine if litter size reduction (LSR) or intrauterine growth restriction (IUGR) alters NPY signaling pathways in the kidney.
- To assess the functional consequences of these alterations on renal function.
Main Methods:
- Induced IUGR in rats via maternal protein restriction.
- Manipulated postnatal environment by reducing litter size (LSR6, LSR10) or using home-cage controls.
- Analyzed NPY, NPY receptors (Y1, Y2), dipeptidylpeptidase IV (DPPIV), and MAPK signaling at Day 70.
- Assessed renal function, including electrolyte excretion (kaliuresis, natriuresis).
Main Results:
- LSR to 6 neonates, but not IUGR, increased NPY mRNA and decreased NPY receptors Y1 and Y2.
- LSR reduced DPPIV expression and altered mitogen-activated protein kinase 42/44 signaling.
- Renal function was impaired in LSR rats, showing increased kaliuresis and natriuresis at Day 70.
Conclusions:
- Early postnatal environmental factors, such as LSR, dysregulate NPY signaling in the kidney.
- These changes in tubular function due to postnatal environment may predispose to kidney pathology.
- NPY signaling is a critical pathway mediating the long-term effects of early life stress on renal health.
Background:
Intrauterine growth restriction (IUGR) is associated with an increased risk of renal diseases in adulthood. However, while low-birth-weight-infants often undergo accelerated postnatal growth, the impact of postnatal environmental factors such as nutrition and early postnatal stressors on renal development and function remains unclear. In this context, Neuropeptide Y (NPY) may act as a critical factor. NPY is a sympathetic coneurotransmitter involved in blood pressure regulation and tubular function. Yet, little is known about the expression and function of endogenous NPY in the kidney and the functional relevance for the transmission of persistent postnatal-induced effects.
Methods:
(1) IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. (2) Litter size was reduced to 6 (LSR6) or 10 (LSR10) male neonates. To differentiate the effect of postnatal nutrition and stressors, we additionally included home-cage-control animals without any postnatal manipulation. Animals were sacrificed at Day 70.
Results:
Litter size reduction (LSR) to 6 but not IUGR increased messenger RNA expression of endogenous NPY and down-regulated the NPY-receptors Y1 and Y2. Furthermore, dipeptidylpeptidase IV (DPPIV)--an enzyme that cleaves NPY--was decreased after LSR. Expression and the phosphorylation of mitogen-activated protein kinase 42/44 (intracellular signalling pathway of the receptor Y1) were altered. An impaired renal function with pronounced kaliuresis and natriuresis was observed at Day 70 after LSR.
Conclusions:
Postnatal nutrition and stressors such as LSR lead to dysregulated signalling of NPY. These data demonstrate that factors in the early postnatal environment exert important changes in the tubular function, which may predispose to corresponding pathology.
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