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  1. Article ; Online: Drosophila melanogaster Neuromuscular Junction as a Model to Study Synaptopathies and Neuronal Autophagy.

    Chakravorty, Anushka / Sheeba, Vasu / Manjithaya, Ravi

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2761, Page(s) 97–120

    Abstract: Neuronal synapse dysfunction is a key characteristic of several neurodegenerative disorders, such as Alzheimer's disease, spinocerebellar ataxias, and Huntington's disease. Modeling these disorders to study synaptic dysfunction requires a robust and ... ...

    Abstract Neuronal synapse dysfunction is a key characteristic of several neurodegenerative disorders, such as Alzheimer's disease, spinocerebellar ataxias, and Huntington's disease. Modeling these disorders to study synaptic dysfunction requires a robust and reproducible method for assaying the subtle changes associated with synaptopathies in terms of structure and function of the synapses. Drosophila melanogaster neuromuscular junctions (NMJs) serve as good models to study such alterations. Further, modifications in the microenvironment of synapses can sometimes reflect in the behavior of the animal, which can also be assayed in a high-throughput manner. The methods outlined in this chapter highlight assays to study the behavioral changes associated with synaptic dysfunction in a spinocerebellar ataxia type 3 (SCA3) model. Further, molecular assessment of alterations in NMJ structure and function is also summarized, followed by effects of autophagy pathway upregulation in providing neuroprotection. These methods can be further extended and modified to study the therapeutic effects of drugs or small molecules in providing neuroprotection for any synaptopathy models.
    MeSH term(s) Animals ; Drosophila melanogaster/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Neuromuscular Junction/metabolism ; Synapses/metabolism ; Autophagy
    Chemical Substances Drosophila Proteins
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3662-6_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Drosophila

    Dani, Chitrang / Sheeba, Vasu

    Frontiers in physiology

    2022  Volume 13, Page(s) 954731

    Abstract: Circadian clocks are considered an evolutionary adaptation to environmental cycles, helping organisms to adapt to daily and seasonal changes. However, most studies on the evolution of circadian rhythms have been carried out in controlled laboratory ... ...

    Abstract Circadian clocks are considered an evolutionary adaptation to environmental cycles, helping organisms to adapt to daily and seasonal changes. However, most studies on the evolution of circadian rhythms have been carried out in controlled laboratory conditions; hence evolution of circadian clocks and rhythms in organisms reared under the influence of naturally varying time cues is not well understood. To address this, we reared large outbred fly populations in an outdoor enclosure on our institutional grounds in Bengaluru, southern India for about 150 generations, at the same time maintaining their ancestral control populations under standard laboratory conditions. Studying their rhythms in eclosion, a vital behavior for
    Language English
    Publishing date 2022-07-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.954731
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Subset of Circadian Neurons Expressing

    Iyengar, Aishwariya Srikala / Rao, Sushma / Sheeba, Vasu

    Journal of biological rhythms

    2023  Volume 38, Issue 4, Page(s) 341–357

    Abstract: Under conditions of prolonged durations of warmth, flies counter potential temperature stress by shifting their locomotor activity from day into night when the conditions are likely to be less harsh. Modulation of a rhythmic behavior such as this in ... ...

    Abstract Under conditions of prolonged durations of warmth, flies counter potential temperature stress by shifting their locomotor activity from day into night when the conditions are likely to be less harsh. Modulation of a rhythmic behavior such as this in response to the environment would require interaction between at least 2 neuronal systems: (1) a
    MeSH term(s) Animals ; Circadian Clocks ; Circadian Rhythm/physiology ; Drosophila melanogaster/physiology ; Drosophila Proteins/metabolism ; Neurons/physiology ; Temperature ; TRPA1 Cation Channel/genetics ; TRPA1 Cation Channel/metabolism
    Chemical Substances Drosophila Proteins ; TRPA1 Cation Channel
    Language English
    Publishing date 2023-04-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 896387-3
    ISSN 1552-4531 ; 0748-7304
    ISSN (online) 1552-4531
    ISSN 0748-7304
    DOI 10.1177/07487304231159713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A new player in circadian networks: Role of electrical synapses in regulating functions of the circadian clock.

    Iyer, Aishwarya Ramakrishnan / Sheeba, Vasu

    Frontiers in physiology

    2022  Volume 13, Page(s) 968574

    Abstract: Several studies have indicated that coherent circadian rhythms in behaviour can be manifested only when the underlying circadian oscillators function as a well-coupled network. The current literature suggests that circadian pacemaker neuronal networks ... ...

    Abstract Several studies have indicated that coherent circadian rhythms in behaviour can be manifested only when the underlying circadian oscillators function as a well-coupled network. The current literature suggests that circadian pacemaker neuronal networks rely heavily on communication mediated by chemical synapses comprising neuropeptides and neurotransmitters to regulate several behaviours and physiological processes. It has become increasingly clear that chemical synapses closely interact with electrical synapses and function together in the neuronal networks of most organisms. However, there are only a few studies which have examined the role of electrical synapses in circadian networks and here, we review our current understanding of gap junction proteins in circadian networks of various model systems. We describe the general mechanisms by which electrical synapses function in neural networks, their interactions with chemical neuromodulators and their contributions to the regulation of circadian rhythms. We also discuss the various methods available to characterize functional electrical synapses in these networks and the potential directions that remain to be explored to understand the roles of this relatively understudied mechanism of communication in modulating circadian behaviour.
    Language English
    Publishing date 2022-11-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.968574
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Gap junction protein Innexin2 modulates the period of free-running rhythms in

    Ramakrishnan, Aishwarya / Sheeba, Vasu

    iScience

    2021  Volume 24, Issue 9, Page(s) 103011

    Abstract: A neuronal circuit of ∼150 neurons modulates rhythmic activity-rest behavior ... ...

    Abstract A neuronal circuit of ∼150 neurons modulates rhythmic activity-rest behavior of
    Language English
    Publishing date 2021-08-20
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2021.103011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Restoration of Sleep and Circadian Behavior by Autophagy Modulation in Huntington's Disease.

    Sharma, Ankit / Narasimha, Kavyashree / Manjithaya, Ravi / Sheeba, Vasu

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2023  Volume 43, Issue 26, Page(s) 4907–4925

    Abstract: Circadian and sleep defects are well documented in Huntington's disease (HD). Modulation of the autophagy pathway has been shown to mitigate toxic effects of mutant Huntingtin (HTT) protein. However, it is not clear whether autophagy induction can also ... ...

    Abstract Circadian and sleep defects are well documented in Huntington's disease (HD). Modulation of the autophagy pathway has been shown to mitigate toxic effects of mutant Huntingtin (HTT) protein. However, it is not clear whether autophagy induction can also rescue circadian and sleep defects. Using a genetic approach, we expressed human mutant HTT protein in a subset of
    MeSH term(s) Animals ; Male ; Humans ; Huntington Disease ; Drosophila/metabolism ; Sleep ; Circadian Rhythm ; Autophagy ; Huntingtin Protein/genetics ; Disease Models, Animal
    Chemical Substances Huntingtin Protein
    Language English
    Publishing date 2023-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.1894-22.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: VANESSA-Shiny Apps for Accelerated Time-series Analysis and Visualization of

    Ghosh, Arijit / Sheeba, Vasu

    Journal of biological rhythms

    2022  Volume 37, Issue 2, Page(s) 222–231

    Abstract: Chronobiologists and sleep researchers often need to estimate various rhythm and sleep parameters from locomotor activity data from different organisms. The available open-source or expensive paid tools do not offer consolidated analysis and ... ...

    Abstract Chronobiologists and sleep researchers often need to estimate various rhythm and sleep parameters from locomotor activity data from different organisms. The available open-source or expensive paid tools do not offer consolidated analysis and visualization options in one bundle, are often cumbersome for users unfamiliar with coding, offer very low customization options, introduce sources of human errors by requiring users to manually pick period and power values from periodogram plots, and do not generate reproducible reports. We present VANESSA, a family of cross-platform apps written in R, which, in our opinion, have several advantages compared with available tools-(a) open-source; (b) automatic period-power detection; (c) time-series filtering and smoothing; (d) high-resolution publication-quality figures with dynamic coloring, resizing, and light/dark shading; (e) reproducible code-report generation; (f) analysis and visualization of multiple monitor files, defining genotypes and replicates separately; and (g) sleep profile analysis, various sleep parameter estimations, quantification, bout analysis, and latency analysis. The current version of the app is for data acquired through
    MeSH term(s) Animals ; Circadian Rhythm ; Drosophila ; Sleep
    Language English
    Publishing date 2022-02-25
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 896387-3
    ISSN 1552-4531 ; 0748-7304
    ISSN (online) 1552-4531
    ISSN 0748-7304
    DOI 10.1177/07487304221077662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Glutamatergic Synapse Dysfunction in

    Chakravorty, Anushka / Sharma, Ankit / Sheeba, Vasu / Manjithaya, Ravi

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 842772

    Abstract: Glutamate is the major excitatory neurotransmitter in the nervous system, and ... ...

    Abstract Glutamate is the major excitatory neurotransmitter in the nervous system, and the
    Language English
    Publishing date 2022-07-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.842772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Gap junction protein Innexin2 modulates the period of free-running rhythms in Drosophila melanogaster

    Aishwarya Ramakrishnan / Vasu Sheeba

    iScience, Vol 24, Iss 9, Pp 103011- (2021)

    2021  

    Abstract: Summary: A neuronal circuit of ∼150 neurons modulates rhythmic activity-rest behavior of Drosophila melanogaster. While it is known that coherent ∼24-hr rhythms in locomotion are brought about when 7 distinct neuronal clusters function as a network due ... ...

    Abstract Summary: A neuronal circuit of ∼150 neurons modulates rhythmic activity-rest behavior of Drosophila melanogaster. While it is known that coherent ∼24-hr rhythms in locomotion are brought about when 7 distinct neuronal clusters function as a network due to chemical communication amongst them, there are no reports of communication via electrical synapses made up of gap junctions. Here, we report that gap junction proteins, Innexins play crucial roles in determining the intrinsic period of activity-rest rhythms in flies. We show the presence of Innexin2 in the ventral lateral neurons, wherein RNAi-based knockdown of its expression slows down the speed of activity-rest rhythm along with alterations in the oscillation of a core-clock protein PERIOD and the output molecule pigment dispersing factor. Specifically disrupting the channel-forming ability of Innexin2 causes period lengthening, suggesting that Innexin2 may function as hemichannels or gap junctions in the clock circuit.
    Keywords Biological sciences ; Physiology ; Neuroscience ; Behavioral neuroscience ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease.

    Prakash, Pavitra / Pradhan, Arpit Kumar / Sheeba, Vasu

    Disease models & mechanisms

    2022  Volume 15, Issue 6

    Abstract: Circadian disturbances are early features of neurodegenerative diseases, including Huntington's disease (HD). Emerging evidence suggests that circadian decline feeds into neurodegenerative symptoms, exacerbating them. Therefore, we asked whether known ... ...

    Abstract Circadian disturbances are early features of neurodegenerative diseases, including Huntington's disease (HD). Emerging evidence suggests that circadian decline feeds into neurodegenerative symptoms, exacerbating them. Therefore, we asked whether known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in a Drosophila circadian HD model. The molecular chaperones Hsp40 and HSP70 emerged as significant suppressors in the circadian context, with Hsp40 being the more potent mitigator. Upon Hsp40 overexpression in the Drosophila circadian ventrolateral neurons (LNv), the behavioural rescue was associated with neuronal rescue of loss of circadian proteins from small LNv soma. Specifically, there was a restoration of the molecular clock protein Period and its oscillations in young flies and a long-lasting rescue of the output neuropeptide Pigment dispersing factor. Significantly, there was a reduction in the expanded Huntingtin inclusion load, concomitant with the appearance of a spot-like Huntingtin form. Thus, we provide evidence implicating the neuroprotective chaperone Hsp40 in circadian rehabilitation. The involvement of molecular chaperones in circadian maintenance has broader therapeutic implications for neurodegenerative diseases. This article has an associated First Person interview with the first author of the paper.
    MeSH term(s) Animals ; Circadian Rhythm/genetics ; Drosophila ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Humans ; Huntington Disease/metabolism ; Neurodegenerative Diseases/metabolism ; Neurons/metabolism
    Chemical Substances Drosophila Proteins
    Language English
    Publishing date 2022-06-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2451104-3
    ISSN 1754-8411 ; 1754-8403
    ISSN (online) 1754-8411
    ISSN 1754-8403
    DOI 10.1242/dmm.049447
    Database MEDical Literature Analysis and Retrieval System OnLINE

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