Neurophysiological Treatment Effects of Mesdopetam, Pimavanserin and Amantadine in a Rodent Model of Levodopa-Induced Dyskinesia.

Levodopa provides effective symptomatic treatment for Parkinson's disease. However, nonmotor symptoms are often insufficiently relieved, and its long-term use is complicated by motor fluctuations and dyskinesia. To clarify mechanisms of levodopa-induced dyskinesia and pharmacological interventions aimed at reducing dyskinetic symptoms, we have here characterized the neurophysiological activity patterns in sensorimotor and cognitive-limbic circuits in dyskinetic rats, comparing the effects of amantadine, pimavanserin, and the novel prospective antidyskinetic and antipsychotic treatment mesdopetam.

The behavioural consequences of dystrophinopathy.

Duchenne muscular dystrophy is a severe neuromuscular disorder, caused by mutations in the DMD gene. Normally, the DMD gene gives rise to many dystrophin isoforms, of which multiple are expressed in the brain. The location of the mutation determines the number of dystrophin isoforms affected, and the absence thereof leads to behavioral and cognitive impairments.

Two orthogonal differentiation gradients locally coordinate fruit morphogenesis.

Morphogenesis requires the coordination of cellular behaviors along developmental axes. In plants, gradients of growth and differentiation are typically established along a single longitudinal primordium axis to control global organ shape. Yet, it remains unclear how these gradients are locally adjusted to regulate the formation of complex organs that consist of diverse tissue types.

Neurophysiological treatment effects of mesdopetam, pimavanserin and clozapine in a rodent model of Parkinson's disease psychosis.

Psychosis in Parkinson's disease is a common phenomenon associated with poor outcomes. To clarify the pathophysiology of this condition and the mechanisms of antipsychotic treatments, we have here characterized the neurophysiological brain states induced by clozapine, pimavanserin, and the novel prospective antipsychotic mesdopetam in a rodent model of Parkinson's disease psychosis, based on chronic dopaminergic denervation by 6-OHDA lesions, levodopa priming, and the acute administration of an NMDA antagonist. Parallel recordings of local field potentials from eleven cortical and sub-cortical regions revealed shared neurophysiological treatment effects for the three compounds, despite their different pharmacological profiles, involving reversal of features associated with the psychotomimetic state, such as a reduction of aberrant high-frequency oscillations in prefrontal structures together with a decrease of abnormal synchronization between different brain regions.