Study summary · research use only
Aicar effect in early neuronal development
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This human cell-line study examined the effect of AICAR on differentiation of NT2/D1 embryonic carcinoma cells exposed to 10-µM retinoic acid (RA), with or without 25-µM AICAR added to the culture medium, in relation to Lesch-Nyhan disease (LND). The authors report that RA-induced differentiation significantly increased expression of MAP2, NRG1, NRP1, NRP2, NEUROG1, and EN1 genes compared with undifferentiated cells, and that AICAR increased expression of the SHH gene and the WNT2 and WNT7B genes but did not influence expression of genes whose overexpression characterizes early neurodevelopmental processes. The authors describe the relevance of these SHH and Wnt/β-catenin pathway changes to LND physiopathology as warranting further exploration.
Abstract
The neurological manifestations of Lesch-Nyhan disease (LND) have been attributed to the effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency on nervous system development. An increase has been reported in the levels of 5-aminoimidazole-4-carboxamide-1-β-D-ribotide (AICAR) and its triphosphate form ZTP in the red blood cells of patients with LND. AICAR accumulation in the brain has been hypothesized as the cause of some of the neurological symptoms of patients with LND. In this study, we examined the effect of AICAR on the differentiation of neurons in the well-established human NTERA-2 cl.D1 (NT2/D1) embryonic carcinoma neurogenesis model. NT2/D1 cells were differentiated along neuroectodermal lineages after exposure to 10-µM retinoic acid (RA), with or without the addition of 25-µM AICAR to the culture medium. The effect of AICAR on RA differentiation were examined through changes in the expression of genes essential to neuronal differentiation, as well as genes from the Wnt/β-catenin, transforming growth factor beta (TGFβ) and sonic hedgehog (SHH) pathways. Results: RA-induced differentiation in the NT2/D1 cells significantly increased the expression of MAP2, NRG1, NRP1, NRP2, NEUROG1 and EN1 genes (genes linked to neural differentiation) compared with undifferentiated NT2/D1 cells. We found that AICAR increased the expression of the SHH gene and the WNT2 and WNT7B genes but did not influence the expression of genes whose overexpression characterize early neurodevelopmental processes. Conclusion: The relevance of the AICAR related changes in the SHH and Wnt/β-catenin pathway genes expression in the physiopathology of LND warrants further exploration.
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