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Catecholamine exocytosis is diminished in R6/2 Huntington’s disease model mice
Author(s) -
Johnson Michael A.,
Villanueva Melissa,
Haynes Christy L.,
Seipel Andrew T.,
Buhler Leah A.,
Wightman R. Mark
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04908.x
Subject(s) - exocytosis , catecholamine , huntington's disease , endocrinology , medicine , dopamine , extracellular , dopaminergic , chemistry , chromaffin cell , secretion , vesicular transport protein , vesicle , biology , adrenal medulla , biochemistry , disease , membrane
In this work, the mechanisms responsible for dopamine (DA) release impairments observed previously in Huntington’s disease model R6/2 mice were evaluated. Voltammetrically measured DA release evoked in striatal brain slices from 12‐week old R6/2 mice by a single electrical stimulus pulse was only 19% of wild‐type (WT) control mice. Iontophoresis experiments suggest that the concentration of released DA is not diluted by a larger striatal extracellular volume arising from brain atrophy, but, rather, that striatal dopaminergic terminals have a decreased capacity for DA release. This decreased capacity was not due to an altered requirement for extracellular Ca 2+ , and, as in WT mice, the release in R6/2 mice required functioning vesicular transporters. Catecholamine secretion from individual vesicles was measured during exocytosis from adrenal chromaffin cells harvested from R6/2 and WT mice. While the number of exocytotic events was unchanged, the amounts released per vesicle were significantly diminished in R6/2 mice, indicating that vesicular catecholamines are present in decreased amounts. Treatment of chromaffin cells with 3‐nitropropionic acid decreased the vesicular release amount from WT cells by 50%, mimicking the release observed from untreated R6/2 cells. Thus, catecholamine release from tissues isolated from R6/2 mice is diminished because of impaired vesicle loading.