Morpho-functional analysis of ecto-nucleoside triphosphate diphosphohydrolases in hypothalamic neurons
Frontiers in Systems Neuroscience, 2009
ABSTRACT The recently discovered ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) are ... more ABSTRACT The recently discovered ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) are mostly transmembrane proteins hydrolyzing ATP and producing substrates for the different purinergic receptors. The NTPDase family consists of 8 isoenzymes. In the central nervous system NTPDase1-3 isoenzymes were detected. In our earlier experiments, we mapped the tissue distribution of NTPDase3 in the central nervous system. NTPDase3 immunoreactivity (IR) was detected exclusively in neurons. Further immunohistochemical and electronmicroscopic studies in the ventrobasal hypothalamic area revealed that NTPDase3 is exclusively associated with excitatory neurons; either as a transmembrane protein or as a protein associated with subcellular organella (e.g. associated with ribosomes, in the matrix of certain mitochondria). Our goal was the further functional characterization of hypothalamic NTPDases. 1) With respect to the estrogen sensitivity of the ventrobasal hypothalamus and to its neuroendocrine role in reproductive processes, we examined whether the expression of NTPDase3 is estrogen dependent. 2) As NTPDase3 IR mitochondria were abundant in the hypothalamic excitatory axon terminals, we tested whether mitochondrial respiration in the hypothalamic synaptosoma can be influenced by applying an NTPDase blocking agent. We show that 1) the hypothalamic expression of NTPDase3 is considerably influenced by the actual estrogen level; 2) NTPDase blocking significantly decreases type 3 mitochondrial respiration and the total mitochondrial respiratory capacity. In conclusion, our results indicate that estrogen regulates the mitochondrial expression of NTPDases and therefore influences the mitochondrial energy (ATP) supply necessary for excitatory neurotransmission in the ventrobasal hypothalamus.
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Papers by Laszlo Frenyo