Modulation of RNA processing genes during sleep-dependent memory.

Memory consolidation in can be sleep-dependent or sleep-independent, depending on the availability of food. The anterior posterior (ap) alpha'/beta' (α'/β') neurons of the mushroom body (MB) are required for sleep-dependent memory consolidation in flies fed after training. These neurons are also involved in the increase of sleep after training, suggesting a coupling of sleep and memory.

Sleepiness, not total sleep amount, increases seizure risk.

Sleep loss has been associated with increased seizure risk since antiquity. Despite this observation standing the test of time, how poor sleep drives susceptibility to seizures remains unclear. To identify underlying mechanisms, we restricted sleep in epilepsy models and developed a method to identify spontaneous seizures using quantitative video tracking.

Time-of-day specificity of anticancer drugs may be mediated by circadian regulation of the cell cycle.

Circadian rhythms are an integral part of physiology, underscoring their relevance for the treatment of disease. We conducted cell-based high-throughput screening to investigate time-of-day influences on the activity of known antitumor agents and found that many compounds exhibit daily rhythms of cytotoxicity concomitant with previously reported oscillations of target genes. Rhythmic action of HSP90 inhibitors was mediated by specific isoforms of HSP90, genetic perturbation of which affected the cell cycle.

Ketogenic and anaplerotic dietary modifications ameliorate seizure activity in Drosophila models of mitochondrial encephalomyopathy and glycolytic enzymopathy.

Seizures are a feature not only of the many forms of epilepsy, but also of global metabolic diseases such as mitochondrial encephalomyopathy (ME) and glycolytic enzymopathy (GE). Modern anti-epileptic drugs (AEDs) are successful in many cases, but some patients are refractory to existing AEDs, which has led to a surge in interest in clinically managed dietary therapy such as the ketogenic diet (KD). This high-fat, low-carbohydrate diet causes a cellular switch from glycolysis to fatty acid oxidation and ketone body generation, with a wide array of downstream effects at the genetic, protein, and metabolite level that may mediate seizure protection.

The ATP-sensitive K channel is seizure protective and required for effective dietary therapy in a model of mitochondrial encephalomyopathy.

Effective therapies are lacking for mitochondrial encephalomyopathies (MEs). MEs are devastating diseases that predominantly affect the energy-demanding tissues of the nervous system and muscle, causing symptoms such as seizures, cardiomyopathy, and neuro- and muscular degeneration. Even common anti-epileptic drugs which are frequently successful in ameliorating seizures in other diseases tend to have a lower success rate in ME, highlighting the need for novel drug targets, especially those that may couple metabolic sensitivity to neuronal excitability.