Deletion of oxyR in Legionella pneumophila causes growth defect on agar.

The intracellular pathogen Legionella pneumophila (Lp) is a strict aerobe, surviving and replicating in environments where it frequently encounters reactive oxygen species (ROS), such as the nutrient-poor water environment and its replicative niche inside host cells. In many proteobacteria, the LysR-type regulator OxyR controls the oxidative stress response; however, the importance of the OxyR homologue in Lp is still unclear. Therefore, we undertook the characterization of phenotypes associated with the deletion of oxyR in Lp. Contrary to the wild type, the oxyR deletion mutant exhibits a severe growth defect on charcoal - yeast extract (CYE) agar lacking α-ketoglutarate supplementation. Growth in AYE broth (CYE without agar and charcoal), in amoeba and in human cultured macrophages, and survival in water is unaffected by the deletion. Supplementing CYE agar with antioxidants that neutralize ROS or introducing the oxyR gene in trans rescues the observed growth defect. Moreover, the mutant grows as well as the wild type on CYE plates made with agarose instead of agar, suggesting that a compound present in the latter is responsible for the growth defect phenotype.

Botulinum toxin A injection into the entopeduncular nucleus improves dynamic locomotory parameters in hemiparkinsonian rats.

Parkinson's disease is associated with hyperactivity of the subthalamic nucleus (STN), contributing to motor and gait disturbances. Although deep brain stimulation of the STN alleviates certain motor dysfunction, its specific effect on gait abnormalities remains controversial. This study investigated the long-term changes in locomotion following direct infusions of botulinum toxin-A into the globus pallidus internal segment (GPi) to suppress the flow of information from the STN to the GPi in a hemiparkinsonian rat model. Static and dynamic gait parameters were quantified using a CatWalk apparatus. Interestingly, botulinum toxin-A at 0.5 ng significantly reduced only the dynamic gait parameters of hemiparkinsonian rats at 1 week and 1 month post-infusion, while static gait parameters did not change. This study offers new insights into the complexity of basal ganglia in locomotor control and shows the potential of central infusion of botulinum toxin-A as a novel intervention in the study of experimental hemiparkinson's disease.

Intrapallidal injection of botulinum toxin A recovers gait deficits in a parkinsonian rodent model.

AIM: Modulation of electrical activity in the subthalamic nucleus has been therapeutically effective in Parkinson's disease. Pharmacological manipulation of glutamate release from subthalamic neurons could also favourably alter basal ganglia activity to improve motor symptoms. This study investigates the efficacy of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the globus pallidus internal segment by botulinum toxin A (BoNT-A) in a parkinsonian model. METHODS: Unilateral 6-hydroxydopamine lesioned parkinsonian rodents and controls received microinfusions of BoNT-A or vehicle into the ipsilateral internal globus pallidus (n = 8 per group). Changes in gait were measured by the CatWalk apparatus, along with assessment of apomorphine-induced rotational behaviour prior to and following BoNT-A injection. Immunofluorescent staining for markers of glutamatergic, GABAergic and total terminals was performed at the internal globus pallidus. RESULTS: Administration of a single dose of BoNT-A (0.5 ng) significantly improved the rotational asymmetry and gait abnormalities. Ameliorations in speed, body speed variation, cadence and walking pattern were comparable to pre-lesioned animals, and persisted up to 1 month following BoNT-A injection. These changes are associated to BoNT-A's ability to selectively target glutamatergic terminals. CONCLUSION: Blockade of subthalamic hyperactivity by BoNT-A leads to sufficient reorganization in the basal ganglia needed to generate a consistent rhythmic pattern of walking. This suggests the potential use of intracerebral BoNT-A to produce effective neuromodulation in the parkinsonian brain, as well as expansion into other neurodegenerative disorders linked to excitotoxity.