Ameliorative influence of vildagliptin on genetic model of neurodegenerative diseases in Drosophila melanogaster

2021 ◽  
Vol 55 (2) ◽  
pp. 92-98
Author(s):  
Ismail Ishola ◽  
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Model ◽  
Neuronal Loss ◽  
Dopamine Neurons ◽  
Neuroprotective Activity ◽  
Self Association ◽  
Aβ42 Peptide ◽  
Food Media ◽  
Dose Dependent ◽  
Normal Food

Background:Neurodegenerative disorders (ND) are characterized by progressive loss of selectively vulnerable populations of neurons, which contrasts with select static neuronal loss. Self-association of amyloid-beta(Aβ)orα-synucleinpeptidesintofibrilsand/orplaquelikeaggregatescauses neurotoxicity. Hence, identification of specific compounds that either inhibit the formation of Aβ or α-syn-fibrils makes an appealing therapeutic strategy in the development of drugs. In the present study, we investigated the protective effect of vildagliptin (VDG) (oral hypoglycemic agent) on genetic models of ND in Drosophila melanogaster. Methods: The disease causing human Aβ42 peptide or α-syn was expressed pan-neuronally (elav-GAL4) or dopamine neurons (DDC-GAL4) using the UAS-GAL4 system. Flies were either grown in food media with or without vildagliptin (1, 5, or 10μM). This was followed by fecundity, larva motility and negative geotaxis assay (climbing) as a measure of neurodegeneration. Results:Elav-Gal4<Aβ flies showed significant decrease in larva contraction and motility indicative of neurodegeneration. However, flies grown on vildaglitptin (VDG) showed dose-dependent and significant increase in larva motility in comparison with flies grown on food media only. Interestingly, the treatments did not affect fecundity when compared with normal food control. Moreover, flies grown on VDG showed no significant change in lifespan. DDC-GAL4<α-syn flies showed significant decrease in larva motility and climbing activity which was ameliorated by supplementation of flies food media with VDG suggestive of neuroprotective activity. Conclusion: Findings from this study showed that vildagliptin is a potential neuroprotective agent in genetic or familial forms of neurodegeneration.

EFFECT OF NICOTINE ON SEXUAL BEHAVIOUR OF MUTANT STRAIN (CURLED) OF DROSOPHILLA MELANOGASTER

2018 ◽  
Vol 24 (1) ◽  
Author(s):  
SHAMIM AKHTER CHOUDHARY
Keyword(s):  
Mutant Strain ◽  
Sexual Behaviour ◽  
Virgin Female ◽  
P Value ◽  
Pooled Data ◽  
Mating Latency ◽  
Males And Females ◽  
Food Medium ◽  
Food Media ◽  
Dose Dependent

In the present study, an attempt was made to study the effect of plant extract on Sexual behaviour of Mutant Strain (Curled) of Drosophila melanogaster. The LC50 has been estimated with 1% of the food media. The virgin females and males were isolated and fed with normal food media for three days. Then sub-lethal concentrations of 0.625 μl / 100 ml food, 1.2 μl /100 ml food, 2.5μl /100 / food of nicotine were mixed in food medium and allowed in flies to feed for two days. Then appropriate combination of untreated / treated males and females were introduced into the mating chamber. Courtship latency, mating latency and copulation duration were studied. After observation of the behaviour, mated flies were allowed to produce progeny. The sexual behaviour of bachelor male and virgin female obtained in the progeny was also studied. The pooled data were analyzed by student t-test and the result indicates p-value significant at 0.05 levels. The courtship latency was affected by in treatment but it is neither dose dependent nor sex dependent.

The P-element-induced silencing effect of KP transposons is dose dependent in Drosophila melanogaster

Genome ◽  
2011 ◽  
Vol 54 (9) ◽  
pp. 752-762 ◽  
Author(s):  
Alireza Sameny ◽  
John Locke
Keyword(s):  
Drosophila Melanogaster ◽  
Critical Role ◽  
Mutagenic Effect ◽  
P Element ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
P Elements ◽  
Single Well ◽  
Dose Dependent

Transposable elements are found in the genomes of all eukaryotes and play a critical role in altering gene expression and genome organization. In Drosophila melanogaster, transposable P elements are responsible for the phenomenon of hybrid dysgenesis. KP elements, a deletion-derivative of the complete P element, can suppress this mutagenic effect. KP elements can also silence the expression of certain other P-element-mediated transgenes in a process called P-element-dependent silencing (PDS), which is thought to involve the recruitment of heterochromatin proteins. To explore the mechanism of this silencing, we have mobilized KP elements to create a series of strains that contain single, well-defined KP insertions that show PDS. To understand the quantitative role of KP elements in PDS, these single inserts were combined in a series of crosses to obtain genotypes with zero, one, or two KP elements, from which we could examine the effect of KP gene dose. The extent of PDS in these genotypes was shown to be dose dependent in a logarithmic rather than linear fashion. A logarithmic dose dependency is consistent with the KP products interacting with heterochromatic proteins in a concentration-dependent manner such that two molecules are needed to induce gene silencing.

Virgin Coconut (Cocos nucifera) Oil Attenuates Rotenone-Induced Toxicity in Fruit Flies (Drosophila melanogaster)

2021 ◽  
Vol 2 (1) ◽  
pp. 26-37
Author(s):  
O.O. Dosumu ◽  
◽  
E.N. Akang ◽  
O.K. Idowu ◽  
G.J. Adeyemi
Keyword(s):  
Drosophila Melanogaster ◽  
Cocos Nucifera ◽  
Coconut Oil ◽  
Redox Status ◽  
Fruit Flies ◽  
Dependent Manner ◽  
Toxicity Assay ◽  
Behavioural Test ◽  
Locomotor Deficits ◽  
Dose Dependent

Background: Parkinson's disease (PD) is a multifactorial neurodegenerative disease with pathogenic mechanisms traceable to oxidative damage and mitochondrial dysfunction. Rotenone, a chemical compound commonly found in pesticides, has been found to inhibit mitochondrial complex-I and initiate PD-like symptoms in mammals and several invertebrates. Virgin Coconut Oil (VCNO) obtained from the coconut fruit has been found to possess anti-oxidative and anti-inflammatory properties. Objectives: The present study evaluated the effect of VCNO on rotenone-induced Parkinsonism in fruit flies- Drosophila melanogaster (D. melanogaster). Methods: Canton special (CS) strains of D. melanogaster, aged between 1 to 3 days were orally exposed for 7 days to 0, 250, 500 and 750 μM rotenone diet for toxicity assay, and 0, 2.5, 5 and 10 % w/w VCNO diet for longevity assay. Thereafter, 5 % VCNO diet was selected for evaluation against 500 μM rotenone. Subsequently, behavioural test (negative geotaxis), markers for redox status and enzyme activities were evaluated. Results: The results showed that rotenone induced toxicity in the flies, while VCNO increased the lifespan of D. melanogaster in a dose-dependent manner. In addition, VCNO ameliorated rotenone-induced locomotor deficits, elevated MDA, as well as the depleted GSH levels. It also mitigated the inhibited activities of SOD, CAT and ATPase in the flies. Conclusions: VCNO protected D. melanogaster against rotenone-induced toxicity by extending longevity, preventing locomotor deficits and reducing oxidative stress.

scholarly journals Ibogaine Modifies GDNF, BDNF and NGF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

2018 ◽  
Author(s):  
Soledad Marton ◽  
Bruno González ◽  
Sebastián Rodríguez ◽  
Ernesto Miquel ◽  
Laura Martínez Palma ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Acute Administration ◽  
Dependent Manner ◽  
Self Administration ◽  
Seeking Behavior ◽  
A Site ◽  
Dose Dependent

<p>Ibogaine is a psychedelic alkaloid which has been subject of intense scientific research due to its reported ability to attenuate drug-seeking behavior. Recent work suggested that ibogaine effects on alcohol self-administration in rats was related to the release of Glial Cell Derived Neurotrophic Factor (GDNF) in the Ventral Tegmental Area (VTA), a mesencephalic region which hosts soma of dopamine neurons. It is well known that neurotrophic factors (NFs) mediate the neuroadaptations induced in the mesocorticolimbic dopaminergic system by repeated exposure to drugs. Although previous reports have shown ibogaine´s ability to induce GDNF expression in rat midbrain, there are no studies addressing its effect on the expression of GDNF, Brain Derived Neurotrophic Factor (BDNF) or Nerve Growth Factor (NGF) in distinct regions containing dopaminergic neurons. In this work, we examined the effect of ibogaine acute administration on the expression of these NFs in the VTA, Prefrontal Cortex (PFC), Nucleus Accumbens (NAcc) and the Substantia Nigra (SN). Thus, rats were i.p. treated with ibogaine 20 mg/kg (I<sub>20</sub>), 40 mg/kg (I<sub>40</sub>) or vehicle, and NFs expression was analyzed after 3 and 24 hours. Only at 24 h an increase of the expression for the three NFs were observed in a site and dose dependent manner. Results for GDNF showed that only I<sub>40</sub> selectively upregulated its expression in the VTA and SN. Both doses of ibogaine elicited a large increase in the expression of BDNF in the NAcc, SN and PFC, while a significant effect was found in the VTA only for I<sub>40</sub>. Finally, NGF was found to be upregulated in all regions after I<sub>40</sub>, while a selective upregulation was found in PFC and VTA for the I<sub>20</sub> treatment. An increase in the content of mature GDNF was observed in the VTA but no significant increase in the mature BDNF protein content was found in all the studied areas. Interestingly, an increase in the content of proBDNF was detected in the NAcc for both treatments. Further research is needed to understand the neurochemical bases of these changes, and to confirm their contribution to the anti-addictive properties of ibogaine. </p>

scholarly journals Inhibition of vascular adhesion protein 1 protects dopamine neurons from the effects of acute inflammation and restores habit learning in the striatum

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Serena Becchi ◽  
Alberto Buson ◽  
Bernard W. Balleine
Keyword(s):  
Inflammatory Response ◽  
Functional Decline ◽  
Neuronal Loss ◽  
Dopamine Neurons ◽  
Neural Function ◽  
Adhesion Protein ◽  
Habit Learning ◽  
Inflammatory State ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

Abstract Background Changes in dopaminergic neural function can be induced by an acute inflammatory state that, by altering the integrity of the neurovasculature, induces neuronal stress, cell death and causes functional deficits. Effectively blocking these effects of inflammation could, therefore, reduce both neuronal and functional decline. To test this hypothesis, we inhibited vascular adhesion protein 1 (VAP-1), a membrane-bound protein expressed on the endothelial cell surface, that mediates leukocyte extravasation and induces oxidative stress. Method We induced dopaminergic neuronal loss by infusing lipopolysaccharide (LPS) directly into the substantia nigra (SN) in rats and administered the VAP-1 inhibitor, PXS-4681A, daily. Results LPS produced: an acute inflammatory response, the loss of dopaminergic neurons in the SN, reduced the dopaminergic projection to SN target regions, particularly the dorsolateral striatum (DLS), and a deficit in habit learning, a key function of the DLS. In an attempt to protect SN neurons from this inflammatory response we found that VAP-1 inhibition not only reduced neutrophil infiltration in the SN and striatum, but also reduced the associated striatal microglia and astrocyte response. We found VAP-1 inhibition protected dopamine neurons in the SN, their projections to the striatum and promoted the functional recovery of habit learning. Thus, we reversed the loss of habitual actions, a function usually dependent on dopamine release in DLS and sensitive to striatal dysfunction. Conclusions We establish, therefore, that VAP-1 inhibition has an anti-inflammatory profile that may be beneficial in the treatment of dopamine neuron dysfunction caused by an acute inflammatory state in the brain.

scholarly journals DOSE-DEPENDENT AMELIORATION OF EPIGALLOCATECHIN-3-GALLATE AGAINST SODIUM VALPROATE INDUCED AUTISTIC RATS

2017 ◽  
Vol 9 (4) ◽  
pp. 203
Author(s):  
Palanisamy Kumaravel ◽  
Gabriel Melchias ◽  
Nayagam Vasanth ◽  
Tamilarasan Manivasagam
Keyword(s):  
Body Weight ◽  
Sodium Valproate ◽  
Neurological Disorders ◽  
Epigallocatechin Gallate ◽  
Neuroprotective Activity ◽  
Related Disorder ◽  
Clinical Presentations ◽  
Autistic Symptoms ◽  
Dose Dependent ◽  
The Brain

Objective: Autism is a neurodevelopment related disorder with a range of clinical presentations attending serious behavioral and neurological disorders among young children that now occur at epidemic rates in developing countries, India included. The objective of this research was to study the effect of epigallocatechin gallate (EGCG) on sodium valproate-induced autism rats.Methods: On the 12th day of gestation wistar rats were administered with a single intraperitoneal injection of sodium valproate (VPA) (600 mg/kg body weight), which induced autism. The rats were treated with EGCG in varying doses 1, 2 and 5 mg/kg body weight via oral administration. The neuroprotectivity effect of the EGCG was followed by assessing the neurotransmitters and neurobiochemical activities such as serotonin, glutamate and nitrite levels in hippocampus and cerebellum region of the brain. Results: Early prenatal exposure to VPA provokes autistic symptoms. Induction of autism significantly impinged the neurotransmitters and neurochemicals such as serotonin, glutamate and nitrite levels in the brain (hippocampus and cerebellum) increased significantly in the rats exposed to VPA. After treatment with an effective dose of EGCG 2 mg/kg body weight the neurotransmitters and neurochemicals levels were decreased when compared with control and VPA-exposed rats. Conclusion: EGCG ameliorates and reverses autistic attributes possibly due to its neuroprotective activity which could pave the way for future investigation for the possible therapeutic approach.

scholarly journals FlyRNAi.org—the database of the Drosophila RNAi screening center and transgenic RNAi project: 2021 update

2020 ◽  
Vol 49 (D1) ◽  
pp. D908-D915
Author(s):  
Yanhui Hu ◽  
Aram Comjean ◽  
Jonathan Rodiger ◽  
Yifang Liu ◽  
Yue Gao ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Functional Genomics ◽  
Protein Interactions ◽  
Protein Modification ◽  
Genetic Model ◽  
Online Resources ◽  
Model Species ◽  
Rnai Screening ◽  
Transcriptomics Data

Abstract The FlyRNAi database at the Drosophila RNAi Screening Center and Transgenic RNAi Project (DRSC/TRiP) provides a suite of online resources that facilitate functional genomics studies with a special emphasis on Drosophila melanogaster. Currently, the database provides: gene-centric resources that facilitate ortholog mapping and mining of information about orthologs in common genetic model species; reagent-centric resources that help researchers identify RNAi and CRISPR sgRNA reagents or designs; and data-centric resources that facilitate visualization and mining of transcriptomics data, protein modification data, protein interactions, and more. Here, we discuss updated and new features that help biological and biomedical researchers efficiently identify, visualize, analyze, and integrate information and data for Drosophila and other species. Together, these resources facilitate multiple steps in functional genomics workflows, from building gene and reagent lists to management, analysis, and integration of data.

scholarly journals The Intracellular Symbiont Wolbachia pipientis Enhances Recombination in a Dose-Dependent Manner

Insects ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 284
Author(s):  
Kaeli N. Bryant ◽  
Irene L. G. Newton
Keyword(s):  
Drosophila Melanogaster ◽  
Horizontal Transmission ◽  
Wolbachia Infection ◽  
Wolbachia Strain ◽  
Dependent Manner ◽  
Predator Prey ◽  
Wolbachia Pipientis ◽  
Intracellular Symbiont ◽  
Dose Dependent ◽  
Classical Genetics

Wolbachia pipientis is an intracellular alphaproteobacterium that infects 40%–60% of insect species and is well known for host reproductive manipulations. Although Wolbachia are primarily maternally transmitted, evidence of horizontal transmission can be found in incongruent host–symbiont phylogenies and recent acquisitions of the same Wolbachia strain by distantly related species. Parasitoids and predator–prey interactions may indeed facilitate the transfer of Wolbachia between insect lineages, but it is likely that Wolbachia are acquired via introgression in many cases. Many hypotheses exist to explain Wolbachia prevalence and penetrance, such as nutritional supplementation, protection from parasites, protection from viruses, or direct reproductive parasitism. Using classical genetics, we show that Wolbachia increase recombination in infected lineages across two genomic intervals. This increase in recombination is titer-dependent as the wMelPop variant, which infects at higher load in Drosophila melanogaster, increases recombination 5% more than the wMel variant. In addition, we also show that Spiroplasma poulsonii, another bacterial intracellular symbiont of D. melanogaster, does not induce an increase in recombination. Our results suggest that Wolbachia infection specifically alters its host’s recombination landscape in a dose-dependent manner.

Paraquat Induced dopaminergic neuronal loss in drosophila melanogaster

2007 ◽  
Vol 66 (5) ◽  
pp. 456-457
Author(s):  
Kristen Noel Ameel ◽  
Daria Drobysheva ◽  
Brandon Welch ◽  
Khan Chaichana ◽  
Aloisia Schmid
Keyword(s):  
Drosophila Melanogaster ◽  
Neuronal Loss ◽  
Dopaminergic Neuronal Loss
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