Basal ganglia dopamine loss due to defect in purine recycling

Abstract

Several rare inherited disorders have provided valuable experiments of nature highlighting specific biological processes of particular importance to the survival or function of midbrain dopamine neurons. In both humans and mice, deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) is associated with profound loss of striatal dopamine, with relative preservation of other neurotransmitters. In the current studies of knockout mice, no morphological signs of abnormal development or degeneration were found in an exhaustive battery that included stereological and morphometric measures of midbrain dopamine neurons, electron microscopic studies of striatal axons and terminals, and stains for degeneration or gliosis. A novel culture model involving HPRT-deficient dopaminergic neurons also exhibited significant loss of dopamine without a morphological correlate. These results suggest that dopamine loss in HPRT deficiency has a biochemical rather than anatomical basis and imply that purine recycling to be a biochemical process of particular importance to the function of dopaminergic neurons.

Review: Carbon nanotube based electrochemical sensors for biomolecules

“…Uric acid is the major metabolite of purines, formed from the breakdown of hypoxanthine by hypoxanthine-guanine phosphoribosyl transferase (HGPT) [27]. A deficiency of HGPT can affect dopaminergic neurons and dopamine concentrations [28].…”

Transcriptomic Approach to Lesch-Nyhan Disease

“…[10,11] Several studies have provided converging evidence for dysfunction of dopaminergic neurons and several hypotheses have been postulated to explain such dysfunction. [12–15] Transcription factors, such as engrailed, [10] have been shown to be dysregulated in HPRT-deficient neuronal cells, leading to impaired dopaminergic neurotransmission or early neurodevelopmental problems. [10,16,17] …”

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson’s disease

“…Five recordings were taken at each concentration, with the exception of the 500nM concentration in which recordings were taken with five single-pulse stimulations and one 5 pulse/100Hz stimulation. HPLC in striatal tissue: HPLC for striatal dopamine and DOPAC content was performed as described previously (64). Statistics: All data were analyzed in GraphPad Prism.…”