Exposure of parents to alcohol alters behavior of offspring in zebrafish

Suresh, Shankeerth; Abozaid, Amira; Tsang, Benjamin

doi:10.1016/j.pnpbp.2020.110143

Cited by 12 publications

(6 citation statements)

References 49 publications

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“…Similar to MPE, cross-generational outcomes of BPE have been historically understudied. The single existing study in zebrafish found that male and female BPE offspring displayed decreased swimming speeds, greater immobility, greater turn angles, and greater thigmotaxis, ( Suresh et al, 2021 ) suggesting motor impairment similar to rodent outcomes of PPE discussed above.…”

Section: Animal Models Of Inter- and Transgenerational Chronic Precon...mentioning

confidence: 92%

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Rice,

Gil,

Baratta

et al. 2024

Neurobiology of Stress

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Section: Animal Models Of Inter- and Transgenerational Chronic Precon...mentioning

confidence: 92%

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Rice,

Gil,

Baratta

et al. 2024

Neurobiology of Stress

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“…A lowered intra-individual variance of turning reflected repeatedly performing the same turning behavior, a stereotypy. 53 …”

Section: Methodsmentioning

confidence: 99%

Hybrid Allosteric Modulators of M1 Muscarinic Receptors Enhance Acetylcholine Efficacy and Decrease Locomotor Activity and Turning Behaviors in Zebrafish

Widman,

Ventresca,

Dietrich

et al. 2024

Preprint

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Allosteric modulation of muscarinic acetylcholine receptors (mAChR) has been identified as a potential strategy for regulating cholinergic signaling in the treatment of various neurological disorders. Most positive allosteric modulators (PAMs) of mAChR enhance agonist affinity and potency, while very few PAMs selectively enhance G-protein coupling efficacy (e.g., amiodarone). The key structural features of amiodarone responsible for enhancement of mAChR efficacy were examined in CHO cells expressing M1 receptors. Subsequent incorporation of these structural features into previously identified allosteric modulators of potency (i.e., n-benzyl isatins) generated hybrid ligands that demonstrated similar or better enhancement of mAChR efficacy, lower in vivo toxicity, and higher allosteric binding affinity relative to amiodarone. Notable hybrid ligands include 8a and 8c which respectively demonstrated the strongest binding affinity and the most robust enhancement of mAChR efficacy as calculated from an allosteric operational model. Amiodarone derivatives and hybrid ligands were additionally screened in wildtype zebrafish (Danio rerio) to provide preliminary in vivo toxicity data as well as to observe effects on locomotor and turning behaviors relative to other mAChR PAMs. Several compounds, including 8a and 8c, reduced locomotor activity and increased measures of turning behaviors in zebrafish, suggesting that allosteric modulation of muscarinic receptor efficacy might be useful in the treatment of repetitive behaviors associated with autism spectrum disorder (ASD) and other neuropsychiatric disorders.

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“…Absolute turn angle (TA) and angular velocity provided measures of the extent of turning behavior, while the intra-individual variance of turn angle quantified how consistently (low variance) or inconsistently (high variance) fish turned. A lowered intra-individual variance of turning reflected repeatedly performing the same turning behavior, a stereotypy 53 .…”

Section: Methodsmentioning

confidence: 99%

Allosteric modulators of M1 muscarinic receptors enhance acetylcholine efficacy and decrease locomotor activity and turning behaviors in zebrafish

Widman,

Ventresca,

Dietrich

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Allosteric modulation of muscarinic acetylcholine receptors (mAChR) has been identified as a potential strategy for regulating cholinergic signaling in the treatment of various neurological disorders. Most positive allosteric modulators (PAMs) of mAChR enhance agonist affinity and potency, while very few PAMs (e.g., amiodarone) selectively enhance G protein coupling efficacy. The key structural features of amiodarone responsible for enhancement of mAChR efficacy were examined in CHO cells expressing M1 receptors. Subsequent incorporation of these structural features into previously identified allosteric modulators of potency (i.e., n-benzyl isatins) generated ligands that demonstrated similar or better enhancement of mAChR efficacy, lower in vivo toxicity, and higher allosteric binding affinity relative to amiodarone. Notable ligands include 8a, c which respectively demonstrated the strongest binding affinity and the most robust enhancement of mAChR efficacy as calculated from an allosteric operational model. Amiodarone derivatives and hybrid ligands were additionally screened in wildtype zebrafish (Danio rerio) to provide preliminary in vivo toxicity data as well as to observe effects on locomotor and turning behaviors relative to other mAChR PAMs. Several compounds, including 8a, c, reduced locomotor activity and increased measures of turning behaviors in zebrafish, suggesting that allosteric modulation of muscarinic receptor efficacy might be useful in the treatment of repetitive behaviors associated with autism spectrum disorder (ASD) and other neuropsychiatric disorders.

show abstract

Exposure of parents to alcohol alters behavior of offspring in zebrafish

Cited by 12 publications

References 49 publications

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Hybrid Allosteric Modulators of M1 Muscarinic Receptors Enhance Acetylcholine Efficacy and Decrease Locomotor Activity and Turning Behaviors in Zebrafish

Allosteric modulators of M1 muscarinic receptors enhance acetylcholine efficacy and decrease locomotor activity and turning behaviors in zebrafish

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