Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment.

Dysfunction of mitochondrial complex I (MCI) has been implicated in the degeneration of dopaminergic neurons in Parkinson's disease. Here, we report the effect of expressing MitoLbNOX, a mitochondrial-targeted version of the bacterial enzyme LbNOX, which increases regeneration of NAD+ in the mitochondria to maintain the NAD+/NADH ratio, in dopaminergic neurons with impaired MCI (MCI-Park mice). MitoLbNOX expression did not ameliorate the cellular or behavioral deficits observed in MCI-Park mice, suggesting that alteration of the mitochondrial NAD+/NADH ratio alone is not sufficient to compensate for loss of MCI function in dopaminergic neurons.

Presynaptic Mu Opioid Receptors Suppress the Functional Connectivity of Ventral Tegmental Area Dopaminergic Neurons with Aversion-Related Brain Regions.

Opioid abuse poses a major healthcare challenge. To meet this challenge, the brain mechanisms underlying opioid abuse need to be more systematically characterized. It is commonly thought that the addictive potential of opioids stems from their ability to enhance the activity of ventral tegmental area (VTA) dopaminergic neurons.

Alpha-synuclein seed amplification assays: Data sharing, standardization needed for clinical use.

Alpha-synuclein seed amplification assays can improve neurodegenerative disease diagnosis and care, but widespread use depends on a framework that standardizes protocols and encourages data sharing.

State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.

In the later stages of Parkinson's disease (PD), patients often manifest levodopa-induced dyskinesia (LID), compromising their quality of life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this treatment gap, the intrinsic and synaptic changes in striatal spiny projection neurons (SPNs) triggered by the sustained elevation of dopamine (DA) during dyskinesia were characterized using electrophysiological, pharmacological, molecular and behavioral approaches.