DONALD IELPO

PhD Graduate

PhD program:: XXXIV



Thesis title: The role of miR-34a in stress-induced neurotransmission within Dorsal Raphe Nuclei

Mounting clinical and preclinical evidence support the involvement of non-coding RNAs such as microRNAs (miRs) in the adaptive (and maladaptive) brain responses to stressful stimuli. Among miRs, the miR-34 family has been involved in the neurobiological processes that underlie the regulation of stress response. Here we elucidate the mechanism through which miR-34 family modulates stress-induced neurotransmission and stress-coping behavior. First, we evaluated the expression of miR-34 family in stress-related brain areas and their role in behavioral and neurochemical stress-response. Then, using histological, molecular, and genetic approaches we examined miR-34a cellular localization in the Dorsal Raphe Nuclei (DRN), and we investigated its specific functions on neurotransmission. Finally, we evaluated a potential involvement of miR-34 family in physiological adaptations to chronic stress exposure. We found that, within brain, miR-34 (especially the isoform a) is highly expressed in DRN. Here it plays a modulatory role on Serotoninergic release to projection areas, through a fine inhibitory tuning of GABA release, thus determining the adopted coping response to acute and chronic stressors. Finally, we identified through next-gen RISC-RNA sequencing several miR-34s’ target, that are possibly involved in physiological adaptations to chronic stress. This study points out that miR-34a could be a selective GABAergic regulator of the DRN activity. This factor seems to exert an inhibitory control on GABA neurons within the DRN, that in turn regulates the serotonergic activity and determines the adopted coping response to stressful stimuli.

Research products

  • 11573/1681565 - 2023 - Natural killer cells and innate lymphoid cells 1 tune anxiety-like behavior and memory in mice via interferon-γ and acetylcholine (01a Articolo in rivista)
    GAROFALO, STEFANO; COCOZZA, GERMANA; MORMINO, ALESSANDRO; IELPO, DONALD; ANDOLINA, DIEGO; VENTURA, ROSSELLA; RENZI, MASSIMILIANO; FUCILE, SERGIO; LAFFRANCHI, MATTIA; PIANO MORTARI, EVA; SCIUME', GIUSEPPE; SOZZANI, SILVANO; SANTONI, ANGELA; LIMATOLA, CRISTINA
  • 11573/1073617 - 2018 - MicroRNA-34 Contributes to the Stress-related Behavior and Affects 5-HT Prefrontal/GABA Amygdalar System through Regulation of Corticotropin-releasing Factor Receptor 1 (01a Articolo in rivista)
    ANDOLINA, DIEGO; DI SEGNI, MATTEO; ACCOTO, ALESSANDRA; LO IACONO, LUISA; IELPO, DONALD; PUGLISI ALLEGRA, STEFANO; VENTURA, ROSSELLA
  • 11573/1291946 - 2019 - Sex-dependent effects of early unstable post-natal environment on response to positive and negative stimuli in adult mice (01a Articolo in rivista)
    DI SEGNI, MATTEO; ANDOLINA, DIEGO; D'ADDARIO, SEBASTIAN LUCA; BABICOLA, LUCY; IELPO, DONALD; PASCUCCI, TIZIANA; LO IACONO, LUISA; VENTURA, ROSSELLA
  • 11573/1688726 - 2023 - GABAergic miR-34a regulates Dorsal Raphè inhibitory transmission in response to aversive, but not rewarding, stimuli (01a Articolo in rivista)
    IELPO, DONALD; CATALE, CLARISSA; REVERTE SOLER, INGRID; CABIB, SIMONA; ANTONUCCI, GABRIELLA; VENTURA, ROSSELLA; LO IACONO, LUISA; ANDOLINA, DIEGO
  • 11573/1385630 - 2020 - Correction to: MicroRNA-34 contributes to the stress-related behavior and affects 5-HT prefrontal/GABA amygdalar system through regulation of corticotropin-releasing factor receptor 1 (01b Commento, Erratum, Replica e simili)
    ANDOLINA, DIEGO; LO IACONO, LUISA; IELPO, DONALD; PUGLISI ALLEGRA, STEFANO; VENTURA, ROSSELLA
  • 11573/1385627 - 2020 - Xlr4 as a new candidate gene underlying vulnerability to cocaine effects (01a Articolo in rivista)
    D'ADDARIO, SEBASTIAN LUCA; BABICOLA, LUCY; IELPO, DONALD; LO IACONO, LUISA; ANDOLINA, DIEGO; VENTURA, ROSSELLA
  • 11573/1385624 - 2020 - RISC RNA sequencing in the Dorsal Raphè reveals microRNAs regulatory activities associated with behavioral and functional adaptations to chronic stress (01a Articolo in rivista)
    BABICOLA, LUCY; IELPO, DONALD; D'ADDARIO, SEBASTIAN LUCA; CABIB, SIMONA; VENTURA, ROSSELLA; FERLAZZO, FABIO; ANDOLINA, DIEGO; LO IACONO, LUISA
  • 11573/1542950 - 2021 - MicroRNA-34a regulates 5-HT2C expression in dorsal raphe and contributes to the anti-depressant-like effect of fluoxetine (01a Articolo in rivista)
    LO IACONO, LUISA; IELPO, DONALD; PARISI, CHIARA; ACCOTO, ALESSANDRA; DI SEGNI, MATTEO; BABICOLA, LUCY; D'ADDARIO, SEBASTIAN LUCA; PASCUCCI, TIZIANA; VENTURA, ROSSELLA; ANDOLINA, DIEGO
  • 11573/1574955 - 2021 - Early life adversity affecting the attachment bond alters ventral tegmental area transcriptomic patterning and behavior almost exclusively in female mice (01a Articolo in rivista)
    LO IACONO, LUISA; BABICOLA, LUCY; DI SEGNI, MATTEO; D'ADDARIO, SEBASTIAN LUCA; MUNICCHI, DIANA; IELPO, DONALD; PASCUCCI, TIZIANA; CABIB, SIMONA; FERLAZZO, FABIO; ANDOLINA, DIEGO; VENTURA, ROSSELLA
  • 11573/1571228 - 2021 - Elevated miR-34a expression and altered transcriptional profile are associated with adverse electromechanical remodeling in the heart of male rats exposed to social stress (01a Articolo in rivista)
    ANDOLINA, DIEGO; IELPO, DONALD; VENTURA, ROSSELLA; LO IACONO, LUISA
  • 11573/1667799 - 2022 - Decline of cardiomyocyte contractile performance and bioenergetic function in socially stressed male rats (01a Articolo in rivista)
    IELPO, DONALD; ANDOLINA, DIEGO
  • 11573/1659983 - 2022 - The long-lasting effects of early life adversities are sex dependent: The signature of miR-34a (01a Articolo in rivista)
    D'ADDARIO, SEBASTIAN LUCA; MUNICCHI, DIANA; MANCINI, CAMILLA; IELPO, DONALD; BABICOLA, LUCY; DI SEGNI, MATTEO; LO IACONO, LUISA; FERLAZZO, FABIO; ANDOLINA, DIEGO; VENTURA, ROSSELLA
  • 11573/1307879 - 2019 - MicroRNA-34a regulates the depression-like behavior in mice by modulating the expression of target genes in the Dorsal Raphè (01a Articolo in rivista)
    LO IACONO, LUISA; IELPO, DONALD; ACCOTO, ALESSANDRA; DI SEGNI, MATTEO; BABICOLA, LUCY; D'ADDARIO, SEBASTIAN LUCA; FERLAZZO, FABIO; PASCUCCI, TIZIANA; VENTURA, ROSSELLA; ANDOLINA, DIEGO
  • 11573/1542738 - 2021 - Resilience to anhedonia-passive coping induced by early life experience is linked to a long-lasting reduction of Ih current in VTA dopaminergic neurons: altered Ih current in the VTA of adult resilient-to-depression mice (01a Articolo in rivista)
    D'ADDARIO, SEBASTIAN LUCA; DI SEGNI, MATTEO; LEDONNE, ANNUNZIATA; BABICOLA, LUCY; IELPO, DONALD; ANDOLINA, DIEGO; RAGOZZINO, DAVIDE ANTONIO; RENZI, MASSIMILIANO; VENTURA, ROSSELLA
  • 11573/1487835 - 2021 - Long term effects of early life stress on HPA circuit in rodent models (01a Articolo in rivista)
    BABICOLA, LUCY; VENTURA, ROSSELLA; D'ADDARIO, SEBASTIAN LUCA; IELPO, DONALD; ANDOLINA, DIEGO; DI SEGNI, MATTEO

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