scholarly journals Big Lessons from Tiny Flies: Drosophila Melanogaster as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems

2018 ◽  
Author(s):  
Ameya Kasture ◽  
Thomas Hummel ◽  
Sonja Sucic ◽  
Michael Freissmuth
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Fate ◽  
Genetic Manipulation ◽  
Therapeutic Strategies ◽  
Proof Of Concept ◽  
Neuronal Connectivity ◽  
Genetic Tool ◽  
Human Orthologs ◽  
The Brain

The brain of Drosophila melanogaster is comprised of some 100,00 neurons, 127 and 80 of which are dopaminergic and serotonergic, respectively. Their activity regulates behavioral functions equivalent to those in mammals, e.g. motor activity, reward and aversion, memory formation, feeding, sexual appetite etc. Mammalian dopaminergic and serotonergic neurons are known to be heterogeneous. They differ in their projections and in their gene expression profile. A sophisticated genetic tool box is available, which allows for targeting virtually any gene with amazing precision in Drosophila melanogaster. Similarly, Drosophila genes can be replaced by their human orthologs including disease-associated alleles. Finally, genetic manipulation can be restricted to single fly neurons. This has allowed for addressing the role of individual neurons in circuits, which determine attraction and aversion, sleep and arousal, odor preference etc. Flies harboring mutated human orthologs provide models, which can be interrogated to understand the effect of the mutant protein on cell fate and neuronal connectivity. These models are also useful for proof-of-concept studies to examine the corrective action of therapeutic strategies. Finally, experiments in Drosophila can be readily scaled up to an extent, which allows for drug screening with reasonably high throughput.

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

2019 ◽  
Vol 128 (06/07) ◽  
pp. 388-394
Author(s):  
Helge Müller-Fielitz ◽  
Markus Schwaninger
Keyword(s):  
Energy Homeostasis ◽  
Genetic Manipulation ◽  
Heart Function ◽  
Feedback Regulation ◽  
Target Organs ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Hpt Axis ◽  
The Brain

AbstractThyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

The development of the sensory neuron pattern in the antennal disc of wild-type and mutant (lz3, ssa) Drosophila melanogaster

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1063-1075
Author(s):  
M.C. Lienhard ◽  
R.F. Stocker
Keyword(s):  
Drosophila Melanogaster ◽  
Sensory Neuron ◽  
Antennal Segment ◽  
Wild Type ◽  
Homeotic Mutant ◽  
In The Wild ◽  
The Brain ◽  
Antennal Disc ◽  
Antennal Nerve

The development of the sensory neuron pattern in the antennal disc of Drosophila melanogaster was studied with a neuron-specific monoclonal antibody (22C10). In the wild type, the earliest neurons become visible 3 h after pupariation, much later than in other imaginal discs. They lie in the center of the disc and correspond to the neurons of the adult aristal sensillum. Their axons join the larval antennal nerve and seem to establish the first connection towards the brain. Later on, three clusters of neurons appear in the periphery of the disc. Two of them most likely give rise to the Johnston's organ in the second antennal segment. Neurons of the olfactory third antennal segment are formed only after eversion of the antennal disc (clusters t1-t3). The adult pattern of antennal neurons is established at about 27% of metamorphosis. In the mutant lozenge3 (lz3), which lacks basiconic antennal sensilla, cluster t3 fails to develop. This indicates that, in the wild type, a homogeneous group of basiconic sensilla is formed by cluster t3. The possible role of the lozenge gene in sensillar determination is discussed. The homeotic mutant spineless-aristapedia (ssa) transforms the arista into a leg-like tarsus. Unlike leg discs, neurons are missing in the larval antennal disc of ssa. However, the first neurons differentiate earlier than in normal antennal discs. Despite these changes, the pattern of afferents in the ectopic tarsus appears leg specific, whereas in the non-transformed antennal segments a normal antennal pattern is formed. This suggests that neither larval leg neurons nor early aristal neurons are essential for the outgrowth of subsequent afferents.

scholarly journals Loxl2 is a mediator of cardiac aging in Drosophila melanogaster; genetically examining the role of aging clock genes

2021 ◽  
Author(s):  
Mark J Bouska ◽  
Hua Bai
Keyword(s):  
Drosophila Melanogaster ◽  
Clock Genes ◽  
Turning Points ◽  
Whole Body ◽  
Specific Gene ◽  
Age Related ◽  
Human Orthologs ◽  
Age Range ◽  
Transcriptional Target

Abstract Transcriptomic, proteomic, and methylation aging clocks demonstrate that aging has a predictable preset program, while Transcriptome Trajectory Turning Points indicate that the 20 to 40 age range in humans is the likely stage at which the progressive loss of homeostatic control, and in turn aging, begins to have detrimental effects. Turning points in this age range overlapping with human aging clock genes revealed five candidates that we hypothesized could play a role in aging or age-related physiological decline. To examine these gene’s effects on lifespan and health-span, we utilized whole body and heart specific gene knockdown of human orthologs in Drosophila melanogaster. Whole body Loxl2, fz3, and Glo1 RNAi positively affected lifespan as did heart-specific Loxl2 knockdown. Loxl2 inhibition concurrently reduced age-related cardiac arrythmia and collagen (Pericardin) fiber width. Loxl2 binds several transcription factors in humans and RT-qPCR confirmed that a conserved transcriptional target CDH1 (Drosophila CadN2), has expression levels which correlate with Loxl2 reduction in Drosophila. These results point to conserved pathways and multiple mechanisms by which inhibition of Loxl2 can be beneficial to heart health and organismal aging.

scholarly journals From induction to conduction: how intrinsic transcriptional priming of extrinsic neuronal connectivity shapes neuronal identity

Open Biology ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. 140144 ◽  
Author(s):  
Jeffrey B. Russ ◽  
Julia A. Kaltschmidt
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Neuronal Cell ◽  
Therapeutic Strategies ◽  
Dendritic Morphology ◽  
Neuronal Connectivity ◽  
Synaptic Specificity ◽  
Neuronal Identity ◽  
Axonal Targeting ◽  
Specific Identity

Every behaviour of an organism relies on an intricate and vastly diverse network of neurons whose identity and connectivity must be specified with extreme precision during development. Intrinsically, specification of neuronal identity depends heavily on the expression of powerful transcription factors that direct numerous features of neuronal identity, including especially properties of neuronal connectivity, such as dendritic morphology, axonal targeting or synaptic specificity, ultimately priming the neuron for incorporation into emerging circuitry. As the neuron's early connectivity is established, extrinsic signals from its pre- and postsynaptic partners feedback on the neuron to further refine its unique characteristics. As a result, disruption of one component of the circuitry during development can have vital consequences for the proper identity specification of its synaptic partners. Recent studies have begun to harness the power of various transcription factors that control neuronal cell fate, including those that specify a neuron's subtype-specific identity, seeking insight for future therapeutic strategies that aim to reconstitute damaged circuitry through neuronal reprogramming.

scholarly journals The endocrinology of the brain

2018 ◽  
Vol 7 (12) ◽  
pp. R275-R285 ◽  
Author(s):  
Gareth Leng
Keyword(s):  
Gene Expression ◽  
Information Processing ◽  
Endocrine Cells ◽  
Synaptic Connectivity ◽  
Neuronal Connectivity ◽  
Signalling Molecules ◽  
Full Diversity ◽  
Chemical Synapses ◽  
The Brain

The brain hosts a vast and diverse repertoire of neuropeptides, a class of signalling molecules often described as neurotransmitters. Here I argue that this description entails a catalogue of misperceptions, misperceptions that feed into a narrative in which information processing in the brain can be understood only through mapping neuronal connectivity and by studying the transmission of electrically conducted signals through chemical synapses. I argue that neuropeptide signalling in the brain involves primarily autocrine, paracrine and neurohormonal mechanisms that do not depend on synaptic connectivity and that it is not solely dependent on electrical activity but on mechanisms analogous to secretion from classical endocrine cells. As in classical endocrine systems, to understand the role of neuropeptides in the brain, we must understand not only how their release is regulated, but also how their synthesis is regulated and how the sensitivity of their targets is regulated. We must also understand the full diversity of effects of neuropeptides on those targets, including their effects on gene expression.

scholarly journals The role of cytokines in the processes of adaptive integration of immune and neuroendocrine reactions of the human body

2021 ◽  
Vol 67 (2) ◽  
pp. 4-9
Author(s):  
E. A. Troshina
Keyword(s):  
Immune Responses ◽  
Therapeutic Strategies ◽  
Main Task ◽  
Combined Effects ◽  
Immune Stimulation ◽  
Adaptive Integration ◽  
The Subject ◽  
To Receive ◽  
The Brain

The immune, endocrine and nervous systems are integrated due to the existence of reciprocal pathways for transmitting information about changes in their actual functional state. The main task of the brain is to receive, integrate and store information, and there is strong evidence that this also applies to information obtained through the body’s immune responses. It has been proven that the production of cytokines in the brain can be caused not only by peripheral immune stimulation, but also by the nerve cells themselves, stimulated by certain neurosensory signals. Evolutionarily preserved antihomeostatic mechanisms characteristic of specific diseases are the subject of further research, the results of which may be very important for the development of therapeutic strategies that would prevent the undesirable combined effects of immune and neuroendocrine mediators.

scholarly journals The Role of Lipid Competition for Endosymbiont-Mediated Protection against Parasitoid Wasps in Drosophila

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Juan C. Paredes ◽  
Jeremy K. Herren ◽  
Fanny Schüpfer ◽  
Bruno Lemaitre
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Manipulation ◽  
Pupal Stage ◽  
Parasitoid Wasps ◽  
Wasp Species ◽  
Lipid Quantification ◽  
Asobara Tabida ◽  
Bacterial Endosymbionts ◽  
Cellular Immune

ABSTRACT Insects commonly harbor facultative bacterial endosymbionts, such as Wolbachia and Spiroplasma species, that are vertically transmitted from mothers to their offspring. These endosymbiontic bacteria increase their propagation by manipulating host reproduction or by protecting their hosts against natural enemies. While an increasing number of studies have reported endosymbiont-mediated protection, little is known about the mechanisms underlying this protection. Here, we analyze the mechanisms underlying protection from parasitoid wasps in Drosophila melanogaster mediated by its facultative endosymbiont Spiroplasma poulsonii . Our results indicate that S. poulsonii exerts protection against two distantly related wasp species, Leptopilina boulardi and Asobara tabida . S. poulsonii -mediated protection against parasitoid wasps takes place at the pupal stage and is not associated with an increased cellular immune response. In this work, we provide three important observations that support the notion that S. poulsonii bacteria and wasp larvae compete for host lipids and that this competition underlies symbiont-mediated protection. First, lipid quantification shows that both S. poulsonii and parasitoid wasps deplete D. melanogaster hemolymph lipids. Second, the depletion of hemolymphatic lipids using the Lpp RNA interference ( Lpp RNAi ) construct reduces wasp success in larvae that are not infected with S. poulsonii and blocks S. poulsonii growth. Third, we show that the growth of S. poulsonii bacteria is not affected by the presence of the wasps, indicating that when S. poulsonii is present, larval wasps will develop in a lipid-depleted environment. We propose that competition for host lipids may be relevant to endosymbiont-mediated protection in other systems and could explain the broad spectrum of protection provided. IMPORTANCE Virtually all insects, including crop pests and disease vectors, harbor facultative bacterial endosymbionts. They are vertically transmitted from mothers to their offspring, and some protect their host against pathogens. Here, we studied the mechanism of protection against parasitoid wasps mediated by the Drosophila melanogaster endosymbiont Spiroplasma poulsonii . Using genetic manipulation of the host, we provide strong evidence supporting the hypothesis that competition for host lipids underlies S. poulsonii -mediated protection against parasitoid wasps. We propose that lipid competition-based protection may not be restricted to Spiroplasma bacteria but could also apply other endosymbionts, notably Wolbachia bacteria, which can suppress human disease-causing viruses in insect hosts.

scholarly journals Role of Serotonin Transporter in Eye Development of Drosophila melanogaster

2020 ◽  
Vol 21 (11) ◽  
pp. 4086
Author(s):  
Tuan L. A. Pham ◽  
Tran Duy Binh ◽  
Guanchen Liu ◽  
Thanh Q. C. Nguyen ◽  
Yen D. H. Nguyen ◽  
...  
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Serotonin Transporter ◽  
Compound Eye ◽  
Eye Development ◽  
S Phase ◽  
Eye Disc ◽  
Eye Imaginal Disc ◽  
The Brain

Serotonin transporter (SerT) in the brain is an important neurotransmitter transporter involved in mental health. However, its role in peripheral organs is poorly understood. In this study, we investigated the function of SerT in the development of the compound eye in Drosophila melanogaster. We found that SerT knockdown led to excessive cell death and an increased number of cells in S-phase in the posterior eye imaginal disc. Furthermore, the knockdown of SerT in the eye disc suppressed the activation of Akt, and the introduction of PI3K effectively rescued this phenotype. These results suggested that SerT plays a role in the healthy eye development of D. melanogaster by controlling cell death through the regulation of the PI3K/Akt pathway.

Sign in / Sign up

Export Citation Format

Share Document