Featured Research

from universities, journals, and other organizations

Shedding light on early Parkinson's disease pathology

Date:
April 1, 2013
Source:
IOS Press BV
Summary:
In a mouse model of early Parkinson's disease (PD), animals displayed movement deficits, loss of tyrosine-hydroxylase (TH)-positive fibers in the striatum, and astro-gliosis and micro-gliosis in the substantia nigra (SN), without the loss of nigral dopaminergic neurons. The findings may cast light on the molecular processes involved in the initial stages of PD.

In a mouse model of early Parkinson's disease (PD), animals displayed movement deficits, loss of tyrosine-hydroxylase (TH)-positive fibers in the striatum, and astro-gliosis and micro-gliosis in the substantia nigra (SN), without the loss of nigral dopaminergic neurons. These findings, which may cast light on the molecular processes involved in the initial stages of PD, are available in the current issue of Restorative Neurology and Neuroscience.

Related Articles


"The most intriguing finding of our study was the lack of a significant decrease of TH levels in the SN of the low-dose MPTP-treated mice, suggesting that this treatment does not induce a direct loss of nigral dopaminergic neurons," says Joost Verhaagen PhD, lead investigator of the study. "These findings appear to support the 'dying back' hypothesis of PD, which proposes that the TH-positive terminal loss in the striatum is the first neurodegenerative event in PD, which later induces neuronal degeneration in the SN." Dr. Verhaagen is Head of the Workgroup on Neuroregeneration at the Netherlands Institute for Neuroscience and Professor at the Free University in Amsterdam.

The neurotoxin MPTP (1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine) was used to induce the degenerative changes. Chronic 5 week administration of 25 mg/kg MPTP combined with probenecid (250 mg/kg), which inhibits MPTP clearance and promotes its crossing of the blood-brain barrier, is known to cause dopaminergic neuron degeneration in the SN and decrease striatal dopaminergic nerve terminals. In the current study, 7 mice were treated with 25 mg/kg MPTP plus probenecid, 6 mice received a lower dose of MPTP (15 mg/kg) plus probenecid, and 8 control mice received saline plus probenecid. A grid test, known to be sensitive to striatal dopaminergic input, was used to detect motor deficits.

Immunohistochemical analysis using TH fluorescence revealed that only the higher dose of MPTP produced significant dopaminergic neuronal cell loss in the SN (65% fluorescence loss, p<0.001). The 15 mg/kg dose produced an 18% decline in fluorescence which was not significantly different than control.

Both dose levels significantly reduced TH immunoreactivity of the striatum. The authors believe that the motor deficits seen at both MPTP dose levels relate to the striatal dopamine depletion.

The study is also the first to report that low-dose MPTP produces astrogliosis and microgliosis in the SN and formation of α-synuclein positive inclusions. "The data suggests that gliosis in the substantia nigra plays a prominent initiating role in the introduction of dopaminergic deficits after MPTP treatment, and may be sufficient to significantly reduce TH levels in the striatum," says Dr. Korecka, first author and principal investigator of the study and a post-doctoral fellow at the Netherlands Institute for Neuroscience in Amsterdam.

"We are the first to report that this early PD model provides an interesting window of opportunity to study the mechanisms that underlie the early neurodegenerative events that initiate the cellular death of dopaminergic neurons," write the authors. They suggest that the model can be used to develop potential treatment strategies to counteract early PD cellular changes.


Story Source:

The above story is based on materials provided by IOS Press BV. Note: Materials may be edited for content and length.


Journal Reference:

  1. Joanna A. Korecka, Ruben Eggers, Dick F. Swaab, Koen Bossers, Joost Verhaagen. Modeling early Parkinson’s disease pathology with chronic low dose MPTP treatment. Restorative Neurology and Neuroscience, March 2013; 31: 2 DOI: 10.3233/RNN-110222

Cite This Page:

IOS Press BV. "Shedding light on early Parkinson's disease pathology." ScienceDaily. ScienceDaily, 1 April 2013. <www.sciencedaily.com/releases/2013/04/130401111258.htm>.
IOS Press BV. (2013, April 1). Shedding light on early Parkinson's disease pathology. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2013/04/130401111258.htm
IOS Press BV. "Shedding light on early Parkinson's disease pathology." ScienceDaily. www.sciencedaily.com/releases/2013/04/130401111258.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) — As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) — A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) — Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) — Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins