October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
Dysregulation of the Axonal Trafficking of Nuclear-encoded Mitochondrial mRNA alters Mitochondrial Activity and Mouse Behavior.
| Wednesday, November 06, 2013 — Poster Session I | |||
|---|---|---|---|
4:00 p.m. – 6:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIMH |
NEURO-15 |
Authors
- A N Kar
- C Sun
- K Reichard
- J Pickel
- K Nakazawa
- A E Gioio
- B B Kaplan
Abstract
Local translation of nuclear-encoded mitochondrial mRNAs such as Cytochrome C Oxidase IV (COXIV), and ATP synthase 9 (ATP5G1), play an important role in axonal energy metabolism, function and growth. However, little is known about the functional significance of axonal trafficking of nuclear-encoded mitochondrial mRNAs in vitro and in vivo. Disrupted axonal trafficking of nuclear-encoded mitochondrial mRNAs in neurons resulted in decreases in endogenous axonal COXIV and ATP5G1 mRNA levels, as well as attenuation of axon growth. Additionally, dysregulated axonal trafficking also led to increased levels of reactive oxygen species (ROS) in the axons possibly as a result of mitochondrial dysfunction. To test the significance of dysregulated axonal trafficking in vivo, we generated transgenic mice in which trafficking of nuclear-encoded mitochondrial mRNAs to the axon was disrupted in the forebrain. Consistent with the in vitro studies, we observed increased ROS levels in pre-frontal and frontal cortices of transgenic mice. Behavioral tests revealed the presence of anxiety-like phenotype as assessed by open-field, elevated plus maze, light-dark box tests. Also, results of the forced swim test suggest the presence of depression-like behavior in the transgenice mice. Taken together, these findings suggest an important role for axonal trafficking of nuclear-encoded mitochondrial mRNAs in behavior.
