Anti-Inflammatory Drug Reduces Nerve Death in Mouse Model of Parkinson's Disease

Nov 07, 2006

Using a mouse model which mimics neuronal cell death in the part of the brain associated with Parkinson’s disease (PD), scientists at the Buck Institute have shown for the first time that these neurons die due to inflammation. The study also shows that treatment with the antibiotic/anti-inflammatory drug minocycline, started before symptoms began to appear, reduced neuronal death in these mice.

The findings, published in November 8 edition of the Journal of Neuroscience, provide a glimpse at potential treatment options for humans and highlight the need for pre-symptomatic tests that would identify those at risk for the disease that affects one out of every 100 people over the age of 65.

The research, led by Buck Institute faculty member Julie Andersen, PhD, involved a mutant mouse known as weaver, so named because it exhibits a loss of balance and motor control early in life. In addition to suffering from a genetically programmed loss of neurons in the cerebellum (the portion of the brain attached to the brain stem) that plays an essential role in coordinating movement), the mice also suffer from nerve death in the substantia nigra, a region in the mid-brain which produces the chemical dopamine that regulates motor control. In humans, PD develops when dopamine levels become deficient, resulting in symptoms which include tremor, slowness of movement, rigidity and problems with balance.

After examining the midbrain of the animals for alterations in gene expression, researchers discovered that weaver mice “over-express” particular genes associated with inflammation compared to normal control littermates. Andersen’s team began treating the mice beginning at birth with minocycline, an antibiotic that also has anti-inflammatory properties. At three weeks of age, the treated mice showed a 30% loss of dopamine-producing neurons in the substantia nigra, as compared to a 50% loss commonly seen in mice not treated with the drug.

“It is satisfying to be able to show that inflammation contributes to dopaminergic cell death in the weaver mouse since neuroinflammation is a commonly observed feature in Parkinson’s disease itself. This suggests that the weaver mouse constitutes a good model to explore potential anti-inflammatory treatments for the human disorder,” said Andersen. She added that the findings also highlight the urgent need to develop tests that would identify at an early age, those at risk for PD. “Currently, by the time humans are diagnosed with Parkinson’s disease they have already lost 60% of their dopamine-producing neurons,” said Andersen, “Anti-inflammatory agents would likely be maximally effective if taken before symptoms appear in order to halt disease progression.”

Others joining Andersen in the study include Buck Institute researchers, Jun Peng, Lin Xie, Fang Fen Stevenson and Simon Melov, along with Dino DiMonte of the Parkinson’s Institute. The work was supported by grants from the National Institutes of Health.

Source: Buck Institute for Age Research

Explore further: Platelets modulate clotting behavior by 'feeling' their surroundings

add to favorites email to friend print save as pdf

Related Stories

Animal-free reprogramming of adult cells improves safety

Aug 13, 2014

Human stem cells produced through genetic reprogramming are beset by safety concerns because current techniques alter the DNA of the stem cells and use material from animals to grow them. Now, A*STAR researchers ...

New pathway identified in Parkinson's through brain imaging

Sep 13, 2010

A new study led by researchers at Columbia University Medical Center has identified a novel molecular pathway underlying Parkinson's disease and points to existing drugs which may be able to slow progression of the disease.

Embryonic stem cells: Reprogramming in early embryos

Mar 26, 2014

An Oregon Health & Science University scientist has been able to make embryonic stem cells from adult mouse body cells using the cytoplasm of two-cell embryos that were in the "interphase" stage of the cell ...

Recommended for you

Infant cooing, babbling linked to hearing ability

5 hours ago

Infants' vocalizations throughout the first year follow a set of predictable steps from crying and cooing to forming syllables and first words. However, previous research had not addressed how the amount ...

Developing 'tissue chip' to screen neurological toxins

6 hours ago

A multidisciplinary team at the University of Wisconsin-Madison and the Morgridge Institute for Research is creating a faster, more affordable way to screen for neural toxins, helping flag chemicals that ...

Gene mutation discovered in blood disorder

10 hours ago

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which ...

Airway muscle-on-a-chip mimics asthma

12 hours ago

The majority of drugs used to treat asthma today are the same ones that were used 50 years ago. New drugs are urgently needed to treat this chronic respiratory disease, which causes nearly 25 million people ...

User comments : 0