Rhes influences striatal cAMP/PKA-dependent signaling and synaptic plasticity in a gender-sensitive fashion

Veronica Ghiglieri, Francesco Napolitano, Barbara Pelosi, Chiara Schepisi, Sara Migliarini, Anna Di Maio, Valentina Pendolino, Maria Mancini, Giuseppe Sciamanna, Daniela Vitucci, Giacomo Maddaloni, Carmela Giampà, Francesco Errico, Robert Nisticò, Massimo Pasqualetti, Barbara Picconi, Alessandro Usiello

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mechanisms of gender-specific synaptic plasticity in the striatum, a brain region that controls motor, cognitive and psychiatric functions, remain unclear. Here we report that Rhes, a GTPase enriched in medium spiny neurons (MSNs) of striatum, alters the striatal cAMP/PKA signaling cascade in a gender-specific manner. While Rhes knockout (KO) male mice, compared to wild-type (WT) mice, had a significant basal increase of cAMP/PKA signaling pathway, the Rhes KO females exhibited a much stronger response of this pathway, selectively under the conditions of dopamine/adenosine-related drug challenge. Corticostriatal LTP defects are exclusively found in A2AR/D2R-expressing MSNs of KO females, compared to KO males, an effect that is abolished by PKA inhibitors but not by the removal of circulating estrogens. This suggests that the synaptic alterations found in KO females could be triggered by an aberrant A2AR/cAMP/PKA activity, but not due to estrogen-mediated effect. Consistent with increased cAMP signaling, D1R-mediated motor stimulation, haloperidol-induced catalepsy and caffeine-evoked hyper-activity are robustly enhanced in Rhes KO females compared to mutant males. Thus Rhes, a thyroid hormone-target gene, plays a relevant role in gender-specific synaptic and behavioral responses.

Original languageEnglish
Article number10933
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Jul 20 2015

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Corpus Striatum
Neuronal Plasticity
Estrogens
Catalepsy
Neurons
GTP Phosphohydrolases
Haloperidol
Caffeine
Thyroid Hormones
Knockout Mice
Adenosine
Cognition
Psychiatry
Dopamine
Brain
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • General

Cite this

Rhes influences striatal cAMP/PKA-dependent signaling and synaptic plasticity in a gender-sensitive fashion. / Ghiglieri, Veronica; Napolitano, Francesco; Pelosi, Barbara; Schepisi, Chiara; Migliarini, Sara; Di Maio, Anna; Pendolino, Valentina; Mancini, Maria; Sciamanna, Giuseppe; Vitucci, Daniela; Maddaloni, Giacomo; Giampà, Carmela; Errico, Francesco; Nisticò, Robert; Pasqualetti, Massimo; Picconi, Barbara; Usiello, Alessandro.

In: Scientific Reports, Vol. 5, 10933, 20.07.2015.

Research output: Contribution to journalArticle

Ghiglieri, V, Napolitano, F, Pelosi, B, Schepisi, C, Migliarini, S, Di Maio, A, Pendolino, V, Mancini, M, Sciamanna, G, Vitucci, D, Maddaloni, G, Giampà, C, Errico, F, Nisticò, R, Pasqualetti, M, Picconi, B & Usiello, A 2015, 'Rhes influences striatal cAMP/PKA-dependent signaling and synaptic plasticity in a gender-sensitive fashion', Scientific Reports, vol. 5, 10933. https://doi.org/10.1038/srep10933
Ghiglieri, Veronica ; Napolitano, Francesco ; Pelosi, Barbara ; Schepisi, Chiara ; Migliarini, Sara ; Di Maio, Anna ; Pendolino, Valentina ; Mancini, Maria ; Sciamanna, Giuseppe ; Vitucci, Daniela ; Maddaloni, Giacomo ; Giampà, Carmela ; Errico, Francesco ; Nisticò, Robert ; Pasqualetti, Massimo ; Picconi, Barbara ; Usiello, Alessandro. / Rhes influences striatal cAMP/PKA-dependent signaling and synaptic plasticity in a gender-sensitive fashion. In: Scientific Reports. 2015 ; Vol. 5.
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