 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 14, 2012 |
| Title |
Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Background: Methylphenidate (MPH) a psychostimulant prescribed to manage ADHD symptoms, has been increasingly prescribed to children not meeting the strict criteria for ADHD. It has also been misused as a “cognitive enhancer” and as an alternative to other psychostimulants. Here, we investigate whether chronic or acute administration of methylphenidate in mice at either 1mg/kg or 10mg/kg dosing, affects cell number and gene expression in the basal ganglion.
Methodology/Principal findings: Through the use of stereological counting methods, we observed a significant reduction (~20%) in dopamine neuron numbers in the substantia nigra pars compacta (SNpc) following chronic administration of 10mg/kg MPH. This dosage of MPH also induced a significant increase in the number of morphologically-activated SNpc microglia. Additionally, exposure to either 1mg/kg or 10 mg/kg MPH increased the sensitivity of SNpc dopamine neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced oxidative stress. Unbiased gene screening employing Affymetrix GeneChip® HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN) of mice exposed to 1mg/kg and 10mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2 and th in the substantia nigra (SN) was observed with both acute and chronic dosing of 10mg/kg MPH. We also found an increase in mRNA levels of the pro-inflammatory genes il-6 and tnf-α in the striatum; although these were seen only at an acute dose of 10mg/kg and not following chronic dosing.
Conclusion: Collectively our results suggest that chronic MPH usage in mice, especially at prolonged higher doses, has long-term neurodegenerative consequences.
|
| |
|
| Overall design |
drug treatment: 3 control, 3 low dose treatment, 3 high dose treatment
|
| |
|
| Contributor(s) |
Sadasivan S, Pond BB, Qu C, Pani AK, Jiao Y, Smeyne RJ |
| Citation(s) |
22470460 |
| Submission date |
Nov 10, 2011 |
| Last update date |
Aug 06, 2018 |
| Contact name |
Chunxu Qu |
| E-mail(s) |
chunxu.qu@stjude.org
|
| Phone |
9015952433
|
| Organization name |
St Jude Children's Research Institute
|
| Department |
Pathology
|
| Lab |
Mullighan
|
| Street address |
262 Danny Thomas Pl
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11180 |
[HT_MG-430_PM] Affymetrix HT MG-430 PM Array Plate |
|
| Samples (9)
|
|
| Relations |
| BioProject |
PRJNA148497 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33619_RAW.tar |
19.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...