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Parkinson's TreatmentParkinson’s Treatment looks Positive

Deep brain stimulation decreases movement-related symptoms and improves quality of life for patients who have advanced Parkinson’s disease, UF researchers find.

Researchers from the University of Florida and 14 additional medical centers reported results today in the online version of The Lancet Neurology journal indicating that deep brain stimulation — also known as DBS — is effective at improving motor symptoms and quality of life in patients with advanced Parkinson’s disease.

The study, sponsored by St. Jude Medical Inc., tested the safety and effectiveness of a constant current DBS device developed by St. Jude Medical to manage the symptoms of Parkinson’s disease. The device aimed to reduce tremors, improve the slowness of movement, decrease the motor disability of the disease and reduce involuntary movements called dyskinesia, which are a common side effect of Parkinson’s drugs.


PlaceholderRestricting Calories Reduces Age-Related Nerve Damages

Damage caused by unstable chemical species to nerves outside the brain and spinal cord was reduced when mice had a lifelong reduced-calorie diet.

Aging is associated with protein damage and imbalance in redox status in a variety of cells and tissues, yet little is known about the extent of age-related oxidative stress in the peripheral nervous system. Previously, we showed a drastic decline in the expression of glial and neuronal proteins in myelinated peripheral nerves with age, which is significantly ameliorated by lifelong calorie restriction. The age-related decline in functional molecules is associ- ated with alterations in cellular protein homeostatic mechanisms, which could lead to a buildup of damaged, aggregated proteins. To determine the extent of oxidative damage within myelinated peripheral nerves, we studied sciatic nerves from rats of four different ages (8, 18, 29, and 38 months) maintained on an ad libitum or a 40% calorie-restricted diet. We found a prominent accumulation of polyubiquitinated substrates with age, which are associated with the conglomeration of distended lysosomes and lipofuscin adducts. The occurrence of these structures is notably less frequent within nerves of age-matched rodents kept on a lifelong reduced calorie diet. Markers for lipid peroxidation, inflammation, and immune cell infiltration are all elevated in nerves of ad libitum– fed rats, whereas food restriction is able to attenuate such deleterious processes with age. Together these results show that dietary restriction is an efficient means of defying age-related oxidative damage and maintaining a younger state in peripheral nerves.

Research Paper


PlaceholderGeneration of new neurons in the adult brain may be essential for learning, memory and mood…

Generation of new neurons in the adult brain may be essential for learning, memory, and mood. Emerging evidence also indicates that adult neurogenesis is impaired by exposure to radiation. These new perspectives underscore a previously unappreciated risk to the cognitive function and psychological stability after radiation exposure.

This risk applies to patients undergoing radiation therapy and to astronauts traveling beyond low-Earth orbit. A new reporter mouse line has been generated, by McKnight Brain Institute (MBI) collaborators in the Enikolopov group at the Cold Spring Harbor Laboratory, to identify at-risk populations of stem and progenitor cells in the adult brain (see green cells in the accompanying figure). It was found, in a collaboration involving the MBI, Cold Spring Harbor, Brookhaven National Laboratory, Neuroscience Associates, and Kennedy Space Center investigators, that early neural progenitors are selectively affected by conditions simulating the space radiation environment; this is reflected both in a decrease in the number of these progenitors in the neurogenic regions and in an increase in the number of dying cells in these regions.

Unexpectedly, it was found that quiescent stem-like cells, rather than their rapidly dividing progeny, constitute the most vulnerable cell population, suggesting a profound impact on the subsequent levels of neurogenesis in the irradiated brain. These findings raise important issues about the possible risks facing astronauts on long duration space missions, and patients exposed to radiation during medical procedures. (From Mignone et al., J. Comp. Neurol., 2004; Encinas et al., Exp. Neurology, 2008).


PlaceholderUF Researchers Find Clues to Nicotine Addiction

Key molecule is linked to depressive symptoms of acute nicotine withdrawal and stress-induced relapse after tobacco cessation.

Abstract

The intracranial self-stimulation (ICSS) procedure was used to assess the negative affective state of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. Stress-induced reinstatement of nicotine-seeking was investigated in animals in which responding for intravenously infused nicotine was extinguished by substituting saline for nicotine.

In the ICSS experiments, the nicotinic receptor antagonist mecamylamine elevated the brain reward thresholds of the nicotine- dependent rats but not those of the control rats. The CRF1 receptor antagonist R278995/CRA0450 but not the CRF2 receptor antagonist astressin-2B prevented the elevations in brain reward thresholds associated with precipitated nicotine withdrawal. Furthermore, R278995/ CRA0450 but not astressin-2B prevented stress-induced reinstatement of extinguished nicotine-seeking. Neither R278995/CRA0450 nor astressin-2B affected operant responding for chocolate-flavored food pellets.

These studies indicate that CRF1 receptors but not CRF2 receptors play an important role in the anhedonic-state associated with acute nicotine withdrawal and stress-induced reinstatement of nicotine-seeking.

Research Paper