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Region-specific microRNA alterations in marmosets carrying SLC6A4 polymorphisms are associated with anxiety-like behavior

Abstract : ABSTRACT Human studies have consistently reported that stress-related disorders such as depression and anxiety impinge on the activity of emotion regulation networks including the ventromedial prefrontal cortex (vmPFC). However, molecular heterogeneity within the vmPFC and how these differences affect emotion regulation and behavior have not been elucidated. Marmosets have emerged as a powerful model in translational neuroscience to investigate molecular underpinnings of complex behaviors. Here, we took advantage of naturally occurring genetic polymorphisms in marmoset SLC6A4 gene that have been linked to anxiety-like behaviors. Using FACS-sorted cells from different brain regions, we revealed that marmosets bearing different SLC6A4 variants exhibit distinct miRNAs signatures specifically in neurons of vmPFC area 32, but not in those of closely related vmPFC area 25. We also identified DCC, a gene linked to anxiety and depression, as a downstream target of miRNAs deregulated in area 32. Significantly, we showed that levels of DCC and miRNAs in area 32 were highly correlated to anxiety-like behaviors as well as to the response to citalopram and 5-HT2a antagonists. Our findings establish links between genetic variants, molecular alterations localized to specific vmPFC regions and complex behavioral/pharmacological responses, providing new mechanistic insights into gene-behavior relationships underlying human psychopathology.
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https://hal-amu.archives-ouvertes.fr/hal-03408594
Contributor : Eduardo Gascon Connect in order to contact the contributor
Submitted on : Friday, October 29, 2021 - 11:23:02 AM
Last modification on : Saturday, October 30, 2021 - 3:58:07 AM

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Natalia Popa, Dipankar Bachar, Angela Roberts, Andrea Santangelo, Eduardo Gascon. Region-specific microRNA alterations in marmosets carrying SLC6A4 polymorphisms are associated with anxiety-like behavior. 2021. ⟨hal-03408594⟩

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