KH Britten
Dec 1, 1992; 12:4745-4765
Articles

Speech by Dr Agustín Carstens at the celebration of 25 years of Bank of Mexico independence, Mexico City, 22 November 2019.

The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of rodents expressing l-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression. We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) male rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with l-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single-unit recordings and dendritic spine analyses on striatal medium spiny neurons (MSNs) in drug-naïve rAAV-injected male parkinsonian rats. rAAV-GFP injected LID-resistant hemi-parkinsonian Lewis rats displayed mild LID and no induction of striatal Nurr1 despite receiving a high dose of l-DOPA. However, Lewis rats overexpressing Nurr1 developed severe LID. Nurr1 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in l-DOPA-naïve rats striatal rAAV-Nurr1 overexpression (1) increased cortically-evoked firing in a subpopulation of identified striatonigral MSNs, and (2) altered spine density and thin-spine morphology on striatal MSNs; both phenomena mimicking changes seen in dyskinetic rats. Finally, we provide postmortem evidence of Nurr1 expression in striatal neurons of l-DOPA-treated PD patients. Our data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.

SIGNIFICANCE STATEMENT The transcription factor Nurr1 is ectopically induced in striatal neurons of rats exhibiting levodopa-induced dyskinesia [LID; a side-effect to dopamine replacement strategies in Parkinson's disease (PD)]. Here we asked whether Nurr1 is causing LID. Indeed, rAAV-mediated expression of Nurr1 in striatal neurons was sufficient to overcome LID-resistance, and Nurr1 agonism exacerbated LID severity in dyskinetic rats. Moreover, we found that expression of Nurr1 in l-DOPA naïve hemi-parkinsonian rats resulted in the formation of morphologic and electrophysiological signatures of maladaptive neuronal plasticity; a phenomenon associated with LID. Finally, we determined that ectopic Nurr1 expression can be found in the putamen of l-DOPA-treated PD patients. These data suggest that striatal Nurr1 is an important mediator of the formation of LID.

We see them each and every day: at the grocery store, the farmer’s market and as side orders served with your favourite dish. In many countries, they are part of the cultural heritage and are consumed on a regular basis. In other parts of the world, they hardly garner a mention except when served as soup on a cold winter’s [...]

The oceans have it all: from microscopic life to the largest animal that has ever lived on Earth, from the colourless to the shimmering, from the frozen to the boiling and from the sunlit to the mysterious dark of the deepest parts of the planet. Oceans are an essential component of the Earth's ecosystem -- a source of biodiversity, food, and [...]

All over the world, holidays mean the return of certain specialties: Olivier salad for New Year’s in Russia, Red bean porridge for solstice in Korea, Haleem for Ramadan in India and the Middle East, Mince pies for Christmas in England, Pogača bread for Orthodox Easter, Banana cakes for Lunar New Year in Vietnam. Whatever the holiday is and wherever in [...]

After abdicating the British throne, Edward was appointed governor of the Bahamas, where he temporarily lived in a lavish home in Nassau

The exact molecule behind the Minamata mercury disaster, caused by a chemical plant’s wastewater, remains a point of disagreement

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The classically trained actor is reading a sonnet a day on Instagram

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Narrated by Smithsonian Distinguished Scholar Richard Kurin, the 24-part video series blends history with modern mainstays

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With Washington, D.C. COVID-19 state of emergency, Smithsonian officials say museums to close Saturday, March 14; events canceled through May 3

In an official statement, the Institution announced temporary closures beginning Saturday, March 14

How do you select one image to represent half a century of photography and art? You don’t

When this publication first appeared five decades ago, it was happy to join the fray

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The new viruses are not harmful to humans or closely related to SARS-CoV-2, the coronavirus that causes COVID-19

Test your mettle with this puzzle created exclusively for our readers

Find the capital cities, working from a list of state names

These paintings, sculptures and illustrations honor the bonds of motherhood

Tour a gallery of presidential portraits, print a 3-D model of a fossil or volunteer to transcribe historical documents

The Beatles guitarist visited his sister in southern Illinois just months before he'd become world famous

In a nation under quarantine, chronicling a crisis demands careful strategy

See how researchers at Smithsonian's National Zoo are trying to glean insight into elephant foraging behavior and more.

The Northwoods League announced Thursday that its 2020 season will not begin on May 26, as originally scheduled, due to the COVID-19 pandemic.

Parents-to-be who will have their new child delivered at the Thunder Bay Regional Health Sciences Centre have to follow a different set of guidelines than found at many other hospitals across Ontario.

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Mar del Plata, Argentinien :: Eine Gemeinde hört von Ländern, die keinen Zugang zum Evangelium haben

A doctor on Manitoulin Island is encouraging seasonal residents to stay home and not to come visit during the COVID-19 pandemic.

A new study facilitated by the Workplace Safety and Insurance Board of Ontario states miners who were forced to inhale an aluminum powder were found to have a higher risk of Parkinson’s disease.

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The following is a post by Kristi Finefield, Reference Specialist in the Prints & Photographs Division, and member of the Picture This blog team. Images have a way of opening our eyes to new aspects of a well-known story. When I think of singer Marian Anderson, an image of her performing at the Lincoln Memorial […]

The following is a post by Kristi Finefield, Reference Specialist in the Prints & Photographs Division, and member of the Picture This blog team. As the Library of Congress marks its 220th year, we take the opportunity to explore one example of its efforts to sustain and celebrate the arts in its physical spaces. Above […]

Our ongoing celebration of the Library of Congress National Book Festival continues with two-time Pulitzer Prize-winning novelist Colson Whitehead discussing "Zone One" on the Poetry & Prose stage at the 2012 Festival.

British product designer Lucy Hughes has invented a biodegradable plastic made from fish offcuts

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Neil Ferguson (date: 5/9/2020 - Rank: 8)

Tourism Cavendish Beach says it is hopeful the Confederation Bridge and province will reopen to certain visitors as soon as it is safe to do so.

Nearly 5 ½ years ago, the water source for the city of Flint was switched in an effort to save money. A disaster followed resulting in deaths, illness and mistrust of government. Tuesday at 10:00 p.m. on WKAR-TV, the documentary series Frontlin e examines the crisis by bringing to light conversations and documents never seen on television before. We spoke with Abby Ellis, the Michigan native who is the film’s director.

National Basketball Association executives and player agents are calling on the league to cancel the remainder of the 2019-20 season due to health concerns over the novel coronavirus outbreak, CNBC reported on Thursday.

LACO AT HOME Features Sheku Kanneh-Mason Interview and Performance & More  Broadway World