Animals ; Drosophila Proteins ; genetics ; metabolism ; Drosophila melanogaster ; Memory ; physiology ; Mushroom Bodies ; cytology ; metabolism ; Proteins ; genetics ; metabolism

Aging is the single most important risk factor that increases susceptibility to many forms of diseases. As such, much effort has been put forward to elucidate the mechanisms behind the processes of aging and to discover novel compounds that retain antiaging activities. Korean red ginseng has been used for a variety of medical purposes in eastern countries for several thousands of years. It has been shown that Korean red ginseng affects a number of biological activities including, but not limited to, anti-inflammatory, anti-oxidative and anti-diabetic pathways. However, few studies have been performed to evaluate its anti-aging effects with an in vivo system. Here Drosophila melanogaster as an in vivo model organism demonstrates that Korean red ginseng tonic extends lifespan, increases resistance to starvation stress and prevents weight gain. This data suggest that Korean red ginseng may regulate organisms' metabolism in favor of extending lifespan.
Aging ; Drosophila ; Drosophila melanogaster ; Metabolism ; Models, Animal ; Panax* ; Risk Factors ; Starvation ; Weight Gain

Animals ; Codon, Nonsense ; Disease ; genetics ; Drosophila ; genetics ; metabolism ; Drosophila Proteins ; genetics ; Humans ; Pseudogenes ; Receptors, Odorant ; genetics

The gastrointestinal tract is the largest digestive organ and the largest immune organ and detoxification organ, which is vital to the health of the body. Drosophila is a classic model organism, and its gut is highly similar to mammalian gut in terms of cell composition and genetic regulation, therefore can be used as a good model for studying gut development. target of rapmaycin complex 1 (TORC1) is a key factor regulating cellular metabolism. Nprl2 inhibits TORC1 activity by reducing Rag GTPase activity. Previous studies have found that nprl2 mutated Drosophila showed aging-related phenotypes such as enlarged foregastric and reduced lifespan, which were caused by over-activation of TORC1. In order to explore the role of Rag GTPase in the developmental defects of the gut of nprl2 mutated Drosophila, we used genetic hybridization combined with immunofluorescence to study the intestinal morphology and intestinal cell composition of RagA knockdown and nprl2 mutated Drosophila. The results showed that RagA knockdown alone could induce intestinal thickening and forestomach enlargement, suggesting that RagA also plays an important role in intestinal development. Knockdown of RagA rescued the phenotype of intestinal thinning and decreased secretory cells in nprl2 mutants, suggesting that Nprl2 may regulate the differentiation and morphology of intestinal cells by acting on RagA. Knockdown of RagA did not rescue the enlarged forestomach phenotype in nprl2 mutants, suggesting that Nprl2 may regulate forestomach development and intestinal digestive function through a mechanism independent of Rag GTPase.
Animals ; Drosophila/genetics* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mammals/metabolism* ; Carrier Proteins ; Tumor Suppressor Proteins/metabolism* ; Drosophila Proteins/genetics*

The mushroom body (MB), a bilateral brain structure possessing about 2000-2500 neurons per hemisphere, plays a central role in olfactory learning and memory in Drosophila melanogaster. Extensive studies have demonstrated that three major types of MB neurons (α/β, α'/β' and Γ) exhibit distinct functions in memory processing, including the critical role of approximately 1000 MB α/β neurons in retrieving long-term memory. Inspired by recent findings that MB α/β neurons can be further divided into three subdivisions (surface, posterior and core) and wherein the α/β core neurons play an permissive role in long-term memory consolidation, we examined the functional differences of all the three morphological subdivisions of MB α/β by temporally precise manipulation of their synaptic outputs during long-term memory retrieval. We found the normal neurotransmission from a combination of MB α/β surface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory, whereas output from MB α/β posterior or core subdivision alone is dispensable. These results imply a specific requirement of about 500 MB α/β neurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MB α/β region.
Adenylyl Cyclases ; metabolism ; Animals ; Drosophila Proteins ; metabolism ; Drosophila melanogaster ; cytology ; metabolism ; physiology ; Memory, Long-Term ; physiology ; Mushroom Bodies ; cytology ; physiology ; Neurons ; cytology ; metabolism ; Synapses ; metabolism ; Transcription Factors ; metabolism

Alzheimer's disease (AD) pathogenesis is characterized by senile plaques in the brain and evidence of oxidative damage. Oxidative stress may precede plaque formation in AD; however, the link between oxidative damage and plaque formation remains unknown. Presenilins are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer's disease. Presenilins physically interact with two antioxidant enzymes thiol-specific antioxidant (TSA) and proliferation-associated gene (PAG) of the peroxiredoxin family. The functional consequences of these interactions are unclear. In the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the fly. This caused phenotypes typical of Notch signaling loss-of-function mutations. We found that while expression of TSA or PAG alone produced no phenotype, co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-of-function phenotype. This phenotype was more severe and more penetrant than that caused by the expression of Psn alone. In order to determine whether these phenotypes were indeed affecting Notch signaling, this experiment was performed in a genetic background carrying an activated Notch (Abruptex) allele. The phenotypes were almost completely rescued by this activated Notch allele. These results link peroxiredoxins with the in vivo function of Presenilin, which ultimately connects two key pathogenetic mechanisms in AD, namely, antioxidant activity and plaque formation, and raises the possibility of a role for peroxiredoxin family members in Alzheimer's pathogenesis.
Amino Acid Sequence ; Animals ; Drosophila ; metabolism ; physiology ; Drosophila Proteins ; metabolism ; Molecular Sequence Data ; Peroxiredoxins ; chemistry ; genetics ; metabolism ; Presenilins ; chemistry ; metabolism ; Receptors, Notch ; metabolism ; Sequence Alignment ; Signal Transduction

The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death. Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis. Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis, and the crosstalk between the Hippo signaling pathway and other major signaling pathways, i.e. Wnt, Notch and Jak/Stat signaling pathways in intestinal compartment.
Animals ; Cell Transformation, Neoplastic ; Drosophila ; Drosophila Proteins ; metabolism ; Homeostasis ; Intestinal Mucosa ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Nuclear Proteins ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Regeneration ; Signal Transduction

RecQ5 in mammalian cells has been suggested to suppress inappropriate homologous recombination. However, the specific pathway(s) in which it is involved and the underlining mechanism(s) remain poorly understood. We took advantage of genetic tools in Drosophila to investigate how Drosophila RecQ5 (dRecQ5) functions in vivo in homologous recombination-mediated double strand break (DSB) repair. We generated null alleles of dRecQ5 using the targeted recombination technique. The mutant animals are homozygous viable, but with growth retardation during development. The mutants are sensitive to both exogenous DSB-inducing treatment, such as gamma-irradiation, and endogenously induced double strand breaks (DSBs) by I-Sce I endonuclease. In the absence of dRecQ5, single strand annealing (SSA)-mediated DSB repair is compromised with compensatory increases in either inter-homologous gene conversion, or non-homologous end joining (NHEJ) when inter-chromosomal homologous sequence is unavailable. Loss of function of dRecQ5 also leads to genome instability in loss of heterozygosity (LOH) assays. Together, our data demonstrate that dRecQ5 functions in SSA-mediated DSB repair to achieve its full efficiency and in suppression of LOH in Drosophila.
Animals ; DNA Repair ; genetics ; DNA, Single-Stranded ; genetics ; Drosophila Proteins ; genetics ; metabolism ; Drosophila melanogaster ; genetics ; metabolism ; Loss of Heterozygosity ; genetics ; RecQ Helicases ; genetics ; metabolism

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep

Mesenchymal stem cell (MSC) is an adult stem cell which has the multipotential differentiation ability. In vitro experiments demonstrated that MSC is able to differentiate into various lineage cells including bone, cartilage, fat, and muscle cells. In addition, MSC has also been shown to differentiate into neural precursors, cardiomyocytes, liver cells, and possible other cell types. The Notch pathway is a highly conserved signaling mechanism involved in many processes determining cell fate during the animal development, and plays an important role in the regulation of cell differentiation, proliferation and apoptosis. Notch ligands and receptors are both transmembrane proteins, and suggest that Notch-mediated cellular interaction is an important way in cell to cell communication. Studies of Notch function provide evidence that Notch signaling affects various differentiation capabilities of MSC. In this review, the roles of Notch signaling in differentiation of MSC are summarized.
Animals ; Cell Differentiation ; Drosophila ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Receptors, Notch ; metabolism ; Signal Transduction