Habituation in high-throughput genetic model organisms as a tool to investigate the mechanisms of neurodevelopmental disorders

Kepler, Lexis D; McDiarmid, Troy A.; Rankin, Catharine H.

doi:10.1016/j.nlm.2020.107208

Cited by 12 publications

(8 citation statements)

References 60 publications

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“…The behavioral changes involved in habituation are strikingly similar across the entire phylogenetic spectrum, regardless of the complexity of the organism's nervous system. This evidence supports the hypothesis that habituation would be a first filter mechanism, universal to living beings, from which the most complex cognitive processes are deployed (Kepler et al, 2020).…”

supporting

confidence: 84%

ERPs Studies of Short- and Long-Term Habituation in Humans: A Systematic Review

et al. 2022

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Habituation is a type of learning that consists of a decrease in the response to a repetitive stimulus. The traditional view is that habituation comprises two processes: a transitory one called short-term habituation (STH), promoted by stimulus presentations at short intervals, and a more durable one called long-term habituation (LTH), promoted by more spaced repetitions. Due to the importance of time in this distinction and in an attempt to elucidate its underlying mechanisms, several studies have sought to relate habituation to brain activity through the analysis of event-related potentials (ERPs). We performed a systematic review of studies on habituation of ERPs in humans using the PRISMA methodology. A total of 175 articles were evaluated for eligibility and 145 were included. Most of the studies focused on short-term effects, demonstrating habituation in a range of ERP components such as P50, P1, N1, P2, N2, and P3. These studies revealed that STH occurs with intervals ranging from 75 ms to 4 s with an optimal of 500 ms, but it does not with intervals greater than 10 s. There are also some studies showing that the P1, N1, P2, N2, and P3 components exhibit LTH with inter-stimulus intervals between 3 and 10 seconds, but the evidence is yet insufficient to establish a secure conclusion with respect to LTH. We propose that future studies should use a wider range of inter-stimulus intervals with tests of both short-and long-term habituation so that the specific neurophysiological components of each type of habituation could be determined.

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supporting

confidence: 84%

ERPs Studies of Short- and Long-Term Habituation in Humans: A Systematic Review

et al. 2022

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“…However, the effect of most schizophrenia-linked polymorphisms on affected or nearby loci has not been experimentally validated, despite studies suggesting association with different manifestations of the condition (Ripke et al, 2014;Richard et al, 2017). Modeling the habituation deficits of schizophrenic patients (Avery et al, 2019) in simple genetically facile experimental organisms has been proposed as necessary to facilitate understanding of the genetic and mechanistic basis of the disease (McDiarmid et al, 2017;Kepler et al, 2020), and this approach is supported by the extensive conservation of schizophrenia risk genes in model organisms (Kasap et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Loss of the Schizophrenia-Linked Furin Protein from Drosophila Mushroom Body Neurons Results in Antipsychotic-Reversible Habituation Deficits

Foka

Georganta²,

Semelidou³

et al. 2022

J. Neurosci.

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Habituation is a conserved adaptive process essential for incoming information assessment, which drives the behavioral response decrement to recurrent inconsequential stimuli and does not involve sensory adaptation or fatigue. Although the molecular mechanisms underlying the process are not well understood, habituation has been reported to be defective in a number of disorders including schizophrenia. We demonstrate that loss of furin1, the Drosophila homolog of a gene whose transcriptional downregulation has been linked to schizophrenia, results in defective habituation to recurrent footshocks in mixed sex populations. The deficit is reversible by transgenic expression of the Drosophila or human Furin in adult a9/b9 mushroom body neurons and by acute oral delivery of the typical antipsychotic haloperidol and the atypical clozapine, which are commonly used to treat schizophrenic patients. The results validate the proposed contribution of Furin downregulation in schizophrenia and suggest that defective footshock habituation is a Drosophila protophenotype of the human disorder.

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“…An important consideration to highlight is the emergence of new non-mammalian model organisms such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish Danio rerio, which provide numerous experimental advantages for evaluating bioactive compounds including genetic and molecular tractability, and reduced experimental costs compared with conventional animal models (Strange, 2016). Although these organisms are anatomically much simpler than humans and despite their evolutionary distance from mammals, approximately 40-70% of the genes from these microorganisms have human orthologs, and the majority of their genes are homologous to human genes (Strange, 2016;Chowanadisai et al, 2020;Kepler et al, 2020). Notwithstanding the above, further research efforts are required to completely validate the use of these organisms as substitute in vivo models.…”

Section: Future Directionsmentioning

confidence: 99%

Cellular antioxidant effect of bioactive peptides and molecular mechanisms underlying: beyond chemical properties

Aguilar-Toalá

Liceaga

2020

Int J of Food Sci Tech

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Bioactive peptides are known for their chemical antioxidant activities. However, the importance of cellular antioxidant peptides has relatively been overlooked; nevertheless, scientific evidence supporting their potential to prevent chronic diseases associated with oxidative stress is progressively increasing. Cellular in vitro and in vivo studies have demonstrated that antioxidant bioactive peptides possess cellular antioxidant activity, decrease oxidative stress biomarkers (e.g. lipid peroxidation, intracellular ROS levels, apoptosis), increase diverse antioxidant enzymes' activities and modulate levels of antioxidant molecules. These cellular in vitro bioactive properties and in vivo health effects suggest that antioxidant peptides could be used as components of functional foods and contribute to health promotion by improving specific physiological functions. This review highlights the scientific evidence about cellular antioxidant activity of bioactive peptides, their protective effect and underlying molecular mechanisms of action. It also describes the underlying antioxidant mechanisms and the structure-function relationship of antioxidant peptides.

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Habituation in high-throughput genetic model organisms as a tool to investigate the mechanisms of neurodevelopmental disorders

Cited by 12 publications

References 60 publications

ERPs Studies of Short- and Long-Term Habituation in Humans: A Systematic Review

ERPs Studies of Short- and Long-Term Habituation in Humans: A Systematic Review

Loss of the Schizophrenia-Linked Furin Protein from Drosophila Mushroom Body Neurons Results in Antipsychotic-Reversible Habituation Deficits

Cellular antioxidant effect of bioactive peptides and molecular mechanisms underlying: beyond chemical properties

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