A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs

Mohammad, Farhan; Singh, Priyanka; Sharma, Abhay

doi:10.1186/1752-0509-3-11

Cited by 34 publications

(96 citation statements)

References 46 publications

(43 reference statements)

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“…Heads of unmated F 2 males and virgin F 2 females were used for generating microarray profiles. Clustering of these profiles along with previously reported [27] PTZ male profile showed similarity between F 2 male and the latter and between F 1 male and F 1 female ( Fig. 1a ) .…”

Section: Resultssupporting

confidence: 74%

“…These genes were found to enrich a few GO biological processes ( Table S4 , supporting material ). Importantly, PTZ regulated CNS genes [27] showed significant overlap with differentially expressed F 0 testis genes ( Fig. 3 ).…”

Section: Resultsmentioning

confidence: 95%

“…For identifying differentially expressed genes, both false discovery rate (FDR) in SAM and fold change (FC) in Acuity were used separately. Previously, microarray profiling using the same methods used here identified reported no gene as differentially expressed below 96% FDR [27]. In the present SAM analysis, genes were considered differentially expressed if found within 20% FDR in SAM.…”

Section: Methodsmentioning

confidence: 87%

“…Unless mentioned otherwise, previously described materials and methods were used [27]. In brief, RT-PCR amplification reactions were carried out in an ABI Prism 7700 sequence detection system (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

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Detection of Transgenerational Spermatogenic Inheritance of Adult Male Acquired CNS Gene Expression Characteristics Using a Drosophila Systems Model

Sharma

Singh

2009

PLoS ONE

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Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ) induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F1 adults after treating F0 adult males with PTZ and of F2 adults resulting from a cross between F1 males and normal females. Surprisingly, microarray clustering showed F1 male profile as closest to F1 female and F0 male profile closest to F2 male. Differentially expressed genes in F1 males, F1 females and F2 males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F2 males. Next, we generated microarray expression profiles of adult testis from F0 and F1 males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying the phenomenon. The finding that adult acquired transcriptomic alteration in soma is spermatogenically inherited across generations has potential implications in human health and evolution.

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Section: Resultssupporting

confidence: 74%

Section: Resultsmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

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Detection of Transgenerational Spermatogenic Inheritance of Adult Male Acquired CNS Gene Expression Characteristics Using a Drosophila Systems Model

Sharma

Singh

2009

PLoS ONE

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“…Chronic treatment with PTZ for seven days was earlier described to result in a decreased climbing speed in males [ 7 ]. We similarly treated females and measured the climbing speed.…”

Section: Resultsmentioning

confidence: 98%

Gender Differences in a Drosophila Transcriptomic Model of Chronic Pentylenetetrazole Induced Behavioral Deficit

2009

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A male Drosophila model of locomotor deficit induced by chronic pentylenetetrazole (PTZ), a proconvulsant used to model epileptogenesis in rodents, has recently been described. Antiepileptic drugs (AEDs) ameliorate development of this behavioral abnormality. Time-series of microarray profiling of heads of male flies treated with PTZ has shown epileptogenesis-like transcriptomic perturbation in the fly model. Gender differences are known to exist in neurological and psychiatric conditions including epileptogenesis. We describe here the effects of chronic PTZ in Drosophila females, and compare the results with the male model. As in males, chronic PTZ was found to cause a decreased climbing speed in females. In males, overrepresentation of Wnt, MAPK, TGF-beta, JAK-STAT, Cell communication, and Dorso-Ventral axis formation pathways in downregulated genes was previously described. Of these, female genes showed enrichment only for Dorso-Ventral axis formation. Surprisingly, the ribosomal pathway was uniquely overrepresented in genes downregulated in females. Gender differences thus exist in the Drosophila model. Gender neutral, the developmental pathway Dorso-Ventral axis formation may be considered as the candidate causal pathway in chronic pentylenetetrazole induced behavioral deficit. Prior evidence of developmental mechanisms in epileptogenesis may support potential usefulness of the fly model. Given this, gender specific pathways identified here may provide a lead for further understanding brain dimorphism in neuropsychiatric disorders.

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Neuronal mechanisms regulating locomotion in adult Drosophila

Gowda,

Banu,

Hussain

et al. 2024

J of Neuroscience Research

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The coordinated action of multiple leg joints and muscles is required even for the simplest movements. Understanding the neuronal circuits and mechanisms that generate precise movements is essential for comprehending the neuronal basis of the locomotion and to infer the neuronal mechanisms underlying several locomotor‐related diseases. Drosophila melanogaster provides an excellent model system for investigating the neuronal circuits underlying motor behaviors due to its simple nervous system and genetic accessibility. This review discusses current genetic methods for studying locomotor circuits and their function in adult Drosophila. We highlight recently identified neuronal pathways that modulate distinct forward and backward locomotion and describe the underlying neuronal control of leg swing and stance phases in freely moving flies. We also report various automated leg tracking methods to measure leg motion parameters and define inter‐leg coordination, gait and locomotor speed of freely moving adult flies. Finally, we emphasize the role of leg proprioceptive signals to central motor circuits in leg coordination. Together, this review highlights the utility of adult Drosophila as a model to uncover underlying motor circuitry and the functional organization of the leg motor system that governs correct movement.

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A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs

Cited by 34 publications

References 46 publications

Detection of Transgenerational Spermatogenic Inheritance of Adult Male Acquired CNS Gene Expression Characteristics Using a Drosophila Systems Model

Detection of Transgenerational Spermatogenic Inheritance of Adult Male Acquired CNS Gene Expression Characteristics Using a Drosophila Systems Model

Gender Differences in a Drosophila Transcriptomic Model of Chronic Pentylenetetrazole Induced Behavioral Deficit

Neuronal mechanisms regulating locomotion in adult Drosophila

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