Neuroscience 2003 Abstract
| Presentation Number: | 787.8 |
|---|---|
| Abstract Title: | Overexpression of GDNF in double transgenic mice in mesencephalic dopaminergic targets during development induces persistent dopaminergic hyperinnervation in cortex but not striatum. |
| Authors: |
Kholodilov, N. G.*1
; Oo, T. F.1
; Yarygina, O.1
; Dauer, W. T.1,3
; Burke, R. E.1,2
1Dept. Neurol., Columbia Univ, New York, NY 2Dept. Pathology, Columbia Univ, New York, NY 3Dept. Pharmacol., Columbia Univ, New York, NY |
| Primary Theme and Topics |
Development - Trophic Factors and Developmental Cell Death -- Trophic factors and cell death |
| Session: |
787. Trophic Factors & Cell Death III Poster |
| Presentation Time: | Wednesday, November 12, 2003 11:00 AM-12:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # B71 |
| Keywords: | substantia nigra, apoptosis, Parkinson's disease, programmed cell death |
Striatal GDNF is likely to play a role in the regulation of the first phase of natural cell death (NCD) at postnatal day (PND)2 in substantia nigra (SN) dopamine (DA) neurons, because apoptosis is suppressed by injection of GDNF and augmented by neutralizing antibodies (Oo et al., J. Neurosci.,2003). In support of this possibility, double transgenic mice overexpressing GDNF in striatum throughout development demonstrate an increased number of SN DA neurons after the first phase of NCD (Kholodilov et al., SFN’02). However, this increase does not persist into adulthood. We now ask whether overexpression of GDNF in mesencephalic DA neuron targets has a lasting effect on their DA innervation. We performed immunohistochemistry for the dopamine transporter (DAT) on complete sets of striatal coronal sections and quantified the number of DAT- positive punctuate structures (DPPS) by stereology. Overexpression of GDNF did not have an effect on the adult number of striatal DPPS: WT=3.1±0.4 (x106) (DPPS/striatum); DT= 3.4±0.6 (p=0.7, NS). However it did increase the number of DPPS in piriform cortex: WT= 1920±607 DPPS/section; DT= 5440±846 DPPS/section (p= 0.007), a 2.8-fold increase. To determine if this alteration in cortical innervation had a behavioral correlate, we examined both basal activity and response to amphetamine (2 mg/kg). In an open field test both WT and DT mice showed similar basal activity, but amphetamine – induced locomotor activity was significantly higher in DT mice during first hour after injection (p<.001, ANOVA). We conclude that GDNF may play a physiologic role in supporting the viability of postnatal SN DA neurons early in the NCD period. In addition, it has a lasting effect on the extent of DA innervation in target cortex areas, but not in striatum.
Supported by NS26836, NS38370, PDF
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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