TY - JOUR
T1 - Basal ganglia dopamine loss due to defect in purine recycling
AU - Egami, Kiyoshi
AU - Yitta, Silaja
AU - Kasim, Suhail
AU - Lewers, J. Chris
AU - Roberts, Rosalinda C.
AU - Lehar, Mohamed
AU - Jinnah, H. A.
N1 - Funding Information:
We thank Michael Kilbourne for providing the 3 [H]-methoxytetrabenazine and Alfred Heller for the MN9D cell line. We also thank Lee Martin for expert advice on histology. This work was supported by NS01985 and NS40470 from the National Institutes of Health and the Lesch–Nyhan Syndrome Children's Research Foundation.
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.nbd.2007.01.010
DO - 10.1016/j.nbd.2007.01.010
M3 - Article
C2 - 17374562
AN - SCOPUS:34147100640
SN - 0969-9961
VL - 26
SP - 396
EP - 407
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -