Biology subjects

Montano-Rodriguez, A. R.

Publications and source records attributed to Montano-Rodriguez, A. R..

2 recordsLinked to original sources

bioRxiv2024

Serotonin system development and adult function are regulated by GDNF

Cognitive functions, neuropsychiatric disorders and behaviors from feeding to mood relate to the serotonin (5-hydroxytryptamine; 5-HT) system. We report that expression of glial cell line-derived neurotrophic factor (GDNF), a known potent stimulator of the brain dopamine system, correlates with serotonergic markers in humans, and increased GDNF defines a subset of psychiatric patients with a characteristic 5-HT-related gene expression pattern. A similar [~]1.5- to 2-fold upregulation of endogenous GDNF expression in mice increases brain 5-HT levels and function, both developmentally and during adulthood, and modulates response to fluoxetine. Notably, increasing GDNF more than approximately 2-fold does not increase 5-HT further and instead produces an inverted U-shaped curve of 5-HT levels, suggesting why the GDNF/5-HT correlation has remained controversial. Collectively, our data indicate that GDNF levels fine-tune 5-HT system development and adult function while excess GDNF exclusively associates with neuropsychiatric illness, making it an important target for future research.

neuroscience↗

bioRxiv2020

Tumor-free elongation of mammalian nephrogenesis by excess fetal GDNF

Due to poor regenerative capacity of adult kidneys, nephron endowment defined by the nephrogenic program during the fetal period dictates renal and related cardiovascular health throughout life. We show that the neurotropic factor GDNF, which is in clinical trials for Parkinsons disease, is capable of prolonging the nephrogenic program beyond its normal cessation without increasing the risk of kidney tumors. Our data demonstrates that excess GDNF expands the nephrogenic program by maintaining nephron progenitors and nephrogenesis in postnatal mouse kidneys. GDNF, through its transcriptional targets excreted from the adjacent epithelium, has a major effect on nephron progenitor self-renewal and maintenance; abnormally high GDNF inhibits nephron progenitor proliferation, but lowering its level normalizes the nephrogenic program to that permissive for nephron progenitor self-renewal and differentiation. Based on our results, we propose that the lifespan of nephron progenitors is determined by mechanisms related to perception of GDNF and other signaling levels.

developmental biology↗