Genetic alteration in the dopamine transporter differentially affects male and female nigrostriatal transporter systems.

Title

Genetic alteration in the dopamine transporter differentially affects male and female nigrostriatal transporter systems.

Creator

Ji Jing; Bourque Melanie; Di Paolo Therese; Dluzen Dean E

Publisher

Biochemical pharmacology

Date

2009
2009-12

Description

Female mice with a heterozygous mutation of their dopamine transporter (+/- DAT) showed relatively robust reductions in striatal DAT specific binding (38-50%), while +/- DAT males showed modest reductions (24-32%). Significant decreases in substantia nigra DAT specific binding (42%) and mRNA (24%) were obtained in +/- DAT females, but not +/- DAT males (19% and 5%, respectively). The effects of this DAT perturbation upon vesicular monoamine transporter-2 (VMAT-2) function revealed significantly greater reserpine-evoked DA output from +/+ and +/- DAT female as compared to male mice and the DA output profile differed markedly between +/+ and +/- DAT females, but not males. No changes in VMAT-2 protein or mRNA levels were present among these conditions. On the basis of these data, we propose: (1) a genetic mutation of the DAT does not exert equivalent effects upon the DAT in female and male mice, with females being more affected; (2) an alteration in the DAT may also affect VMAT-2 function; (3) this interaction between DAT and VMAT-2 function is more prevalent in female mice; and (4) the +/- DAT mutation affects VMAT-2 function through an indirect mechanism, that does not involve an alteration in VMAT-2 protein or mRNA. Such DAT/VMAT-2 interactions can be of significance to the gender differences observed in drug addiction and Parkinson's disease.

Subject

Animals; Corpus Striatum/*metabolism; Dopamine Plasma Membrane Transport Proteins/*genetics; Female; Male; Messenger/biosynthesis; Mice; Mutant Strains; Protein Binding; Reserpine/pharmacology; RNA; Sex Characteristics; Substantia Nigra/*metabolism; Vesicular Monoamine Transport Proteins/antagonists & inhibitors/biosynthesis/*physiology

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1401–1411

Issue

11

Volume

78

Citation

Ji Jing; Bourque Melanie; Di Paolo Therese; Dluzen Dean E, “Genetic alteration in the dopamine transporter differentially affects male and female nigrostriatal transporter systems.,” NEOMED Bibliography Database, accessed April 23, 2021, https://neomed.omeka.net/items/show/3482.

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