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
Tyrosine hydroxylase is locally synthesized in the axons of noradrenergic sympathetic neurons.
| Wednesday, November 06, 2013 — Poster Session I | |||
|---|---|---|---|
4:00 p.m. – 6:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIMH |
NEURO-11 |
Authors
- N.M. Gervasi
- S.N. Vohra
- M.A. MacGibeny
- M. Patel
- A.N. Kar
- A.E. Gioio
- B.B. Kaplan
Abstract
Altered levels of catecholamines in the central nervous system are implicated in the pathogenesis of a number of neuropsychiatric disorders. With the exception of L-DOPA for Parkinson’s disease, at present no available drugs target the catecholamine biosynthetic pathway. To identify factors that regulate the presynaptic synthesis of catecholamines, we tested the hypothesis that tyrosine hydroxylase (TH) is locally synthesized in axons and presynaptic nerve terminals. Analysis of polysome-bound RNA showed that TH mRNA is bound to polysomes in axons. Elevation of local cAMP levels resulted in a several-fold increase in the relative abundance of TH mRNA in axonal polysomes, suggesting that axonal TH synthesis could be locally regulated. Finally, metabolic labeling of axonally synthesized proteins showed that labeled TH was specifically synthesized in axons. Taken together, our results show that TH mRNA is present and locally translated in axons in vitro. Preliminary data on DOPA decarboxylase and dopamine beta hydroxylase indicate that these enzymes may also be locally synthesized in axons. Regulating the availability of the enzymes of the catecholamine biosynthetic pathway in the pre-synaptic nerve terminal may allow the modulation of local neurotransmitter synthesis and lead to the development of new pharmacological strategies for the treatment of neuropsychiatric disorders.
