Elevated sleep quota in a stress-resilient Drosophila species.

Sleep is broadly conserved across the animal kingdom but can vary widely between species. It is currently unclear which selective pressures and regulatory mechanisms influence differences in sleep between species. The fruit fly Drosophila melanogaster has become a successful model system for examining sleep regulation and function, but little is known about the sleep patterns in many related fly species. Here, we find that fly species with adaptations to extreme desert environments, including D. mojavensis, exhibit strong increases in baseline sleep compared with D. melanogaster. Long-sleeping D. mojavensis show intact homeostasis, indicating that desert flies carry an elevated drive for sleep. In addition, D. mojavensis exhibit altered abundance or distribution of several sleep/wake-related neuromodulators and neuropeptides that are consistent with their reduced locomotor activity and increased sleep. Finally, we find that in a nutrient-deprived environment, the sleep patterns of individual D. mojavensis are strongly correlated with their survival time and that disrupting sleep via constant light stimulation renders D. mojavensis more sensitive to starvation. Our results demonstrate that D. mojavensis is a novel model for studying organisms with high sleep drive and for exploring sleep strategies that provide resilience in extreme environments.

Elevated sleep need in a stress-resilient Drosophila species.

Sleep is broadly conserved across the animal kingdom, but can vary widely between species. It is currently unclear which types of selective pressures and sleep regulatory mechanisms influence differences in sleep between species. The fruit fly Drosophila melanogaster has become a successful model system for examining sleep regulation and function, but little is known about the sleep patterns and need for sleep in many related fly species. Here, we find that Drosophila mojavensis, a fly species that has adapted to extreme desert environments, exhibits strong increases in sleep compared to D. melanogaster. Long-sleeping D. mojavensis show intact sleep homeostasis, indicating that these flies carry an elevated need for sleep. In addition, D. mojavensis exhibit altered abundance or distribution of several sleep/wake related neuromodulators and neuropeptides that are consistent with their reduced locomotor activity, and increased sleep. Finally, we find that in a nutrient-deprived environment, the sleep responses of individual D. mojavensis are correlated with their survival time. Our results demonstrate that D. mojavensis is a novel model for studying organisms with high sleep need, and for exploring sleep strategies that provide resilience in extreme environments.

Presumed Copperhead Snakebite and Antivenom Administration in the Third Trimester.

Snake envenomation during pregnancy is an uncommon emergency with several potential complications associated with the poisoning and its treatment. This case discusses a 27-y-old gravida 3, para 1102 (3 total pregnancies, 1 term birth, 1 premature birth, 0 abortions, 2 living births, twins) at 36 wk gestation who was bitten by a presumed Agkistrodon contortrix (copperhead snake). She had worsening pain and swelling in the right lower limb. Crotalidae polyvalent immune Fab was administered. The patient felt significantly better with improvement in swelling. She had a reactive nonstress test and reassuring coagulation studies. She gave birth to a healthy female infant 12 d later. This case supports the use of Crotalidae polyvalent immune Fab for venomous snakebites in pregnant patients to prevent possible maternal and fetal morbidity and mortality.

The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.

The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice.

The Microbiome and Host Behavior.

The microbiota is increasingly recognized for its ability to influence the development and function of the nervous system and several complex host behaviors. In this review, we discuss emerging roles for the gut microbiota in modulating host social and communicative behavior, stressor-induced behavior, and performance in learning and memory tasks. We summarize effects of the microbiota on host neurophysiology, including brain microstructure, gene expression, and neurochemical metabolism across regions of the amygdala, hippocampus, frontal cortex, and hypothalamus. We further assess evidence linking dysbiosis of the gut microbiota to neurobehavioral diseases, such as autism spectrum disorder and major depression, drawing upon findings from animal models and human trials. Finally, based on increasing associations between the microbiota, neurophysiology, and behavior, we consider whether investigating mechanisms underlying the microbiota-gut-brain axis could lead to novel approaches for treating particular neurological conditions.

Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.

The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes.

Corticotropin-releasing factor (CRF)-induced disruption of attention in rats is blocked by the κ-opioid receptor antagonist JDTic.

Stress often disrupts behavior and can lead to psychiatric illness. Considerable evidence suggests that corticotropin-releasing factor (CRF) plays an important role in regulating the effects of stress. CRF administration produces stress-like effects in humans and laboratory animals, and CRF levels are elevated in individuals with stress-related illness. Recent work indicates that κ-opioid receptor (KOR) antagonists can block CRF effects, raising the possibility that at least some of the effects of stress are mediated via KORs. Here we examined the effects of CRF on performance in the 5-choice serial reaction time task (5CSRTT), a test used to quantify attention in rodents, as well as functional interactions between CRF and KORs. Male Sprague-Dawley rats were trained in the 5CSRTT and then each was implanted with an intracerebroventricular (ICV) cannula. After recovery and restabilization of performance, they received a single intraperitoneal (IP) injection of vehicle or JDTic (10 mg/kg), a KOR antagonist with long-lasting (>14 days) effects. In subsequent sessions, rats received ICV infusions of CRF (0.25-1.0 µg) or vehicle and were tested 60 min later. CRF dose-dependently disrupted performance as reflected by decreases in correct responding, increases in omission errors, increases in latencies to respond correctly, and increases in time to complete the session. JDTic attenuated each of these CRF-induced deficits while having no effects on its own. The persistent ability of JDTic to disrupt KOR function was confirmed using the tail immersion assay. These findings indicate that KOR antagonists can prevent acute stress-related effects that degrade performance in tasks requiring attention.

A sensory code for host seeking in parasitic nematodes.

Parasitic nematode species often display highly specialized host-seeking behaviors that reflect their specific host preferences. Many such behaviors are triggered by host odors, but little is known about either the specific olfactory cues that trigger these behaviors or the underlying neural circuits. Heterorhabditis bacteriophora and Steinernema carpocapsae are phylogenetically distant insect-parasitic nematodes whose host-seeking and host-invasion behavior resembles that of some devastating human- and plant-parasitic nematodes. We compare the olfactory responses of Heterorhabditis and Steinernema infective juveniles (IJs) to those of Caenorhabditis elegans dauers, which are analogous life stages. The broad host range of these parasites results from their ability to respond to the universally produced signal carbon dioxide (CO(2)), as well as a wide array of odors, including host-specific odors that we identified using thermal desorption-gas chromatography-mass spectroscopy. We find that CO(2) is attractive for the parasitic IJs and C. elegans dauers despite being repulsive for C. elegans adults, and we identify a sensory neuron that mediates CO(2) response in both parasitic and free-living species, regardless of whether CO(2) is attractive or repulsive. The parasites' odor response profiles are more similar to each other than to that of C. elegans despite their greater phylogenetic distance, likely reflecting evolutionary convergence to insect parasitism.