Preserved striatal innervation maintains motor function despite severe loss of nigral dopaminergic neurons.

Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations leading to mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E-variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control.

Incorporating a Polyethyleneglycol Linker to Enhance the Hydrophilicity of Mitochondria-Targeted Triphenylphosphonium Constructs.

The targeting of bioactive molecules and probes to mitochondria can be achieved by coupling to the lipophilic triphenyl phosphonium (TPP) cation, which accumulates several hundred-fold within mitochondria in response to the mitochondrial membrane potential (Δψm ). Typically, a simple alkane links the TPP to its "cargo", increasing overall hydrophobicity. As it would be beneficial to enhance the water solubility of mitochondria-targeted compounds we explored the effects of replacing the alkyl linker with a polyethylene glycol (PEG). We found that the use of PEG led to compounds that were readily taken up by isolated mitochondria and by mitochondria inside cells. Within mitochondria the PEG linker greatly decreased adsorption of the TPP constructs to the matrix-facing face of the mitochondrial inner membrane. These findings will allow the distribution of mitochondria-targeted TPP compounds within mitochondria to be fine-tuned.

Mandibular third molars as a risk factor for angle fractures: a retrospective study.

INTRODUCTION: Anecdotal reports suggest that the presence of mandibular third molars predispose the mandible to angle fractures. The purpose of this study was to evaluate the presence of mandibular third molars as a risk factor for angle fractures in patients with fractured mandibles. MATERIALS AND METHOD: A retrospective study was designed comprising of patients admitted for treatment of mandibular fractures between January 2006 and January 2009. Data sources were the patients' medical records and radiographs. The predictor variables were the presence and position of third molar. Third molar position was grouped into 9 categories based on the Winter's and Pell & Gregory classification. The outcome variable was the presence of an angle fracture. Other study variables included age, sex, race and mechanism of injury, associated fractures and fracture location. RESULTS: Of the 136 patients with mandibular third molars, 49 cases had angle fractures. Of the 18 patients without mandibular third molars, 03 had angle fractures. CONCLUSION: The results of this study demonstrate that patients with fractured mandibles and mandibular third molars are nearly 2.2 times more likely to have an angle fracture than patients without mandibular third molars.