Journal of neurogenetics最新文献

Alzheimer's disease (AD) is the leading cause of dementia globally, but effective treatment is lacking. We aimed to explore lncRNA XIST role in AD and the mechanisms involved in the effect of changes in lncRNA XIST on the expression of Aβ-degrading enzymes. The mouse model of AD and the cell model induced by Aβ were established. LncRNA XIST, IDE, NEP, Plasmin, ACE, EZH2 expressions and distribution of XIST in the nucleus and cytoplasm were detected by qRT-PCR. Inflammatory cytokines IL-6, IL-1β, TNFα, IL-8, and Aβ42 levels were detected by ELISA. TUNEL was used to measure brain tissue damage. Cell proliferation was detected by CCK-8 assay. Flow cytometry detected cell apoptosis. RIP validated the combination of XIST and EZH2. ChIP verified that XIST recruits EZH2 to mediate enrichment of HEK27me3 in the NEP promoter region. The protein expression in brain tissues and cells was detected by Western blot. The expression of lncRNA XIST was increased in AD mice and cell models. Inflammation and injury of nerve cells occurred in AD mice and cell models. The knockdown of lncRNA XIST alleviated Aβ-induced neuronal inflammation and damage. LncRNA XIST affected the expression of Aβ-degrading enzyme NEP, and lncRNA XIST was negatively correlated with NEP expression in AD mice. LncRNA XIST regulated NEP expression partly through epigenetic regulation by binding with EZH2. LncRNA XIST mediated neuronal inflammation and injury through epigenetic regulation of NEP. Overall, our study found that lncRNA XIST induced Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in AD.

Deciding whether or not to lay an egg on a given substrate is an important task undertaken by females of many arthropods. It involves perceiving the environment (e.g. quality of the substrate, temperature, and humidity), formulating a decision, and then conducting the appropriate behaviours to oviposit. This oviposition site selection (OSS) provides a useful system for studying simple decision-making. OSS in fruit flies, Drosophila melanogaster, is influenced by both genetic and environmental variation. Naturally occurring allelic variation in the foraging gene (for) is known to affect OSS. Given a choice of high- and low-nutrient oviposition substrates, groups of rovers (for^R) are known to lay significantly more of their eggs on low-nutrient sites than sitters (for^s) and sitter mutants (for^s2). Here we ask three questions: (1) Is the role of for in OSS affected by the availability of alternate oviposition sites? (2) Is the role of for in OSS sensitive to the density of ovipositing females? and (3) Does the gustatory sensation of yeast play a role in for-mediated variation in OSS? We find a role of choice and female density in rover/sitter differences in OSS, as well as a role of for in response to glycerol, an indicator of yeast. The role of for in OSS decision-making is complex and multi-faceted and should prove fertile ground for further research into the factors affecting decision-making behaviours.

The digestion of food and absorption of nutrients occurs in the gut. The nutritional value of food and its nutrients is detected by enteroendocrine cells, and peptide hormones produced by the enteroendocrine cells are thought to be involved in metabolic homeostasis, but the specific mechanisms are still elusive. The enteroendocrine cells are scattered over the entire gastrointestinal tract and can be classified according to the hormones they produce. We followed the changes in combinatorial expression of regulatory peptides in the enteroendocrine cells during metamorphosis from the larva to the adult fruit fly, and re-confirmed the diverse composition of enteroendocrine cell populations. Drosophila enteroendocrine cells appear to differentially regulate peptide expression spatially and temporally depending on midgut region and developmental stage. In the late pupa, Notch activity is known to determine which peptides are expressed in mature enteroendocrine cells of the posterior midgut, and we found that the loss of Notch activity in the anterior midgut results in classes of enteroendocrine cells distinct from the posterior midgut. These results suggest that enteroendocrine cells that populate the fly midgut can differentiate into distinct subtypes that express different combinations of peptides, which likely leads to functional variety depending on specific needs.

A cGMP-dependent protein kinase (PKG) encoded by the Drosophila foraging (for) gene regulates both synaptic structure (nerve terminal growth) and function (neurotransmission) through independent mechanisms at the Drosophila larval neuromuscular junction (nmj). Glial for is known to restrict nerve terminal growth, whereas presynaptic for inhibits synaptic vesicle (SV) exocytosis during low frequency stimulation. Presynaptic for also facilitates SV endocytosis during high frequency stimulation. for's effects on neurotransmission can occur independent of any changes in nerve terminal growth. However, it remains unclear if for's effects on neurotransmission affect nerve terminal growth. Furthermore, it's possible that for's effects on synaptic structure contribute to changes in neurotransmission. In the present study, we examined these questions using RNA interference to selectively knockdown for in presynaptic neurons or glia at the Drosophila larval nmj. Consistent with our previous findings, presynaptic knockdown of for impaired SV endocytosis, whereas knockdown of glial for had no effect on SV endocytosis. Surprisingly, we found that knockdown of either presynaptic or glial for increased neurotransmitter release in response to low frequency stimulation. Knockdown of presynaptic for did not affect nerve terminal growth, demonstrating that for's effects on neurotransmission does not alter nerve terminal growth. In contrast, knockdown of glial for enhanced nerve terminal growth. This enhanced nerve terminal growth was likely the cause of the enhanced neurotransmitter release seen following knockdown of glial for. Overall, we show that for can affect neurotransmitter release by regulating both synaptic structure and function.

The biogenic monoamine octopamine (OA) is a crucial regulator of invertebrate physiology and behavior. Since its discovery in the 1950s in octopus salivary glands, OA has been implicated in many biological processes among diverse invertebrate lineages. It can act as a neurotransmitter, neuromodulator and neurohormone in a variety of biological contexts, and can mediate processes including feeding, sleep, locomotion, flight, learning, memory, and aggression. Here, we focus on the roles of OA in female reproduction in insects. OA is produced in the octopaminergic neurons that innervate the female reproductive tract (RT). It exerts its effects by binding to receptors throughout the RT to generate tissue- and region-specific outcomes. OA signaling regulates oogenesis, ovulation, sperm storage, and reproductive behaviors in response to the female's internal state and external conditions. Mating profoundly changes a female's physiology and behavior. The female's OA signaling system interacts with, and is modified by, male molecules transferred during mating to elicit a subset of the post-mating changes. Since the role of OA in female reproduction is best characterized in the fruit fly Drosophila melanogaster, we focus our discussion on this species but include discussion of OA in other insect species whenever relevant. We conclude by proposing areas for future research to further the understanding of OA's involvement in female reproduction in insects.

Marla Sokolowski's scientific achievements established her as an internationally recognized leader in behavioural genetics. As a graduate student, she made a significant discovery while observing natural populations of the fruit fly, Drosophila melanogaster: the larvae exhibited a behavioural polymorphism which she traced to alleles of a single gene. Some larvae were 'sitters' which fed in a restricted location, while others were 'rovers' which ranged more widely in feeding. The gene in question, foraging, codes for a cyclic GMP kinase which is expressed in numerous locations throughout larval and adult Drosophila. Building on this foundation, she and her students have elucidated the genetic and environmental factors that account for individual differences in behaviour. In this article, I review significant stages of her scientific career.