Acetylcholine and Royal Jelly Fatty Acid Combinations as Potential Dry Eye Treatment Components in Mice

Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Our previous studies have shown that royal jelly (RJ) has restored the capacity for tear secretion by modulating muscarinic calcium signaling. RJ contains acetylcholine, which is a major cholinergic neurotransmitter, and a unique set of fatty acids with C 8 to 12 chains, which are expected to be associated with health benefits. The purpose of the present study was to investigate the active components involved in tear secretion capacity, focusing on acetylcholine and fatty acids in RJ. Using the stress-induced dry-eye model mice, it was confirmed that acetylcholine with three fatty acids (10-hydroxydecanoic acid, 8-hydroxyoctanoic acid, and (R)-3,10-dihydroxydecanoic acid) was essential for tear secretion. In ex vivo Ca2+ imaging, these three fatty acids suppressed the decrease in intracellular modulation of Ca2+ in the lacrimal gland by acetylcholine when treated with acetylcholinesterase, indicating that the specific type of RJ fatty acids contributed to the stability of acetylcholine. To our knowledge, this study is the first to confirm that a specific compound combination is important for the pharmacological activities of RJ. Our results elucidate the active molecules and efficacy mechanisms of RJ.

Unc-4 acts to promote neuronal identity and development of the take-off circuit in the Drosophila CNS

The Drosophila ventral nerve cord (VNC) is composed of thousands of neurons born from a set of individually identifiable stem cells. The VNC harbors neuronal circuits required to execute key behaviors, such as flying and walking. Leveraging the lineage-based functional organization of the VNC, we investigated the developmental and molecular basis of behavior by focusing on lineage-specific functions of the homeodomain transcription factor, Unc-4. We found that Unc-4 functions in lineage 11A to promote cholinergic neurotransmitter identity and suppress the GABA fate. In lineage 7B, Unc-4 promotes proper neuronal projections to the leg neuropil and a specific flight-related take-off behavior. We also uncovered that Unc-4 acts peripherally to promote proprioceptive sensory organ development and the execution of specific leg-related behaviors. Through time-dependent conditional knock-out of Unc-4, we found that its function is required during development, but not in the adult, to regulate the above events.

Unc-4 acts to promote neuronal identity and development of the take-off circuit in the Drosophila CNS

ABSTRACTThe Drosophila ventral nerve cord (VNC), the fly equivalent of the spinal cord, is composed of thousands of neurons that are born from a set of individually identifiable stem cells. The VNC harbors neuronal circuits required for the execution of vital behaviors, such as flying and walking. Taking advantage of the lineage-based functional organization of the VNC and genetic tools we developed, we investigated the molecular and developmental basis of behavior by focusing on lineage-specific functions of the homeodomain transcription factor, Unc-4. We found that Unc-4 functions in lineage 11A to promote cholinergic neurotransmitter identity and suppress the GABA fate. In 7B lineage, Unc-4 promotes proper neuronal projections to the leg neuropil, the hub for leg-related neuronal circuits and a specific flight-related take-off behavior. We also uncovered that Unc-4 acts peripherally to promote the development of proprioceptive sense organs and the abilities of flies to execute specific leg-related behaviors such as walking, climbing, and grooming. Our findings, thus, initiates the work on revealing molecular and developmental events that shape the VNC related behaviors.

Effect of alimentary synthetic estrogen on cell compensatory mechanisms in rats of different ages

Results of a study of lipid peroxidation, antioxidant system components, and cholinergic neurotransmitter system in the organs of experimental rats of different ages exposed to alimentary synthetic estrogen are presented. Given the state of peroxidation processes and AChE activities in female rats exposed to xenoestrogen, it is possible to assume the possibility of the restructuring of the functioning of mediator and enzyme systems and additional strengthening of pathological symptoms. In the future, such phenomena may trigger the reduction of potential of compensatory mechanisms in compromising the health of the consumers. In puberty, females were more sensitive to nutritional synthetic estrogen than mature animals, thus proving that age is another factor in xenoestrogen exposure. Because of the changes in the rates of reactions to detoxification but not to the metabolism of estrogen received into the organism, particularly with food, with age the animals were less susceptible to the effects of these substances.

A cellular and regulatory map of the cholinergic nervous system of C. elegans

Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly.

Pathogenesis of Depression: Clinical Studies

Historically, research focused on themonoaminergicsystemshas contributed to our understanding of theunderlying pathophysiology of affective disorders.Recent directions in clinical and translational research have concentrated on discovering alternative therapeutic targets with the hopes of producing more efficacious and faster-acting antidepressant agents.This chapter offers an overview of recent clinical research targeting the glutamatergic and cholinergic neurotransmitter systems, with particular interest in novel agents that have produced rapid antidepressant effects. Insights into the underlying pathophysiology of mood disorders resulting from this work are reviewed. In addition, the rapidity of clinical response offers the unique opportunity to studybiological markers more efficiently , and to utilize biomarkers to predict treatment outcome. The findings from such studies also are summarized.