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Biology subjects

Sebastiani, A.

Publications and source records attributed to Sebastiani, A..

2 recordsLinked to original sources

Essential Role for Trf2 in Cardiac Development and Function

Telomere Repeat-binding Factor 2 (Trf2) is essential for protecting our telomeres. While Trf2 global deletion is lethal, its role in organ-specific development, particularly in the heart, remains less understood. In this study, we investigated the role of Trf2 in cardiac development and function. Our studies reveal that cardiomyocyte (CM)-specific loss of Trf2 leads to profound defects in heart morphology, including impaired ventricular wall formation and compromised CM proliferation, concurrent with no CM telomere length attrition. Further, in vivo functional assessment and molecular analyses of CM-Trf2 deficient ventricles revealed severe cardiac dysfunction and, interestingly, altered nuclear envelope gene expression, respectively. Our work provides new insights into the essential role of Trf2 in heart development and function, and potential avenues for therapeutic intervention targeting telomere biology.

developmental biology↗

Bumetanide prevents brain trauma-induced depressive-like behavior.

Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels not available. Using controlled-cortical impact (CCI) as experimental model of brain trauma in adult mouse we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on appearance of depression-like behavior. We demonstrate that this alteration in behavior is associated with a block of CCI-induced decrease in parvalbumin-positive interneurons and impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.

neuroscience↗