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DTSTART:20170326T030000
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DTSTART:20171029T020000
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DTSTAMP:20260429T074019Z
UID:5914383947b7c374984062@ist.ac.at
DTSTART:20170523T113000
DTEND:20170523T123000
DESCRIPTION:Speaker: Laura Cancedda\nhosted by Simon Hippenmeyer\nAbstract:
  Down syndrome (DS) is the most frequent genetic cause of intellectual dis
 ability\, and individuals with DS often present also sleep and anxiety dis
 orders. A large body of literature demonstrated that altered GABAergic tra
 nsmission through Cl?- permeable GABAA receptors (GABAARs) considerably co
 ntributes to learning and memory deficits in DS mouse models. However\, th
 e efficacy of GABAergic transmission had never been directly assessed in D
 S. Recently\, we have shown that GABAAR signaling is excitatory rather tha
 n inhibitory\, in the hippocampi of adult DS mice. Accordingly\, hippocamp
 al expression of the cation Cl? cotransporter NKCC1 is increased in both t
 risomic mice and individuals with DS. Notably\, NKCC1 inhibition by the FD
 A-approved diuretic bumetanide restores inhibitory GABAergic signaling\, s
 ynaptic plasticity and hippocampus-dependent memory in adult DS mice. Base
 d on these findings\, a pilot clinical trial will soon start on adult indi
 viduals with DS patients. Yet\, there are open issues related to Cl- homeo
 stasis that\, if addressed in DS mice\, will provide new knowledge into DS
  molecular mechanisms and will offer a larger scientific background for de
 signing future clinical trials. In this talk\, I will summarize all findin
 gs from our laboratory on DS\, and show preliminary results we recently co
 llected on some of these open issues.\n
LOCATION:Seminar Room\, Lab Building East\, ISTA
ORGANIZER:ddomniso@ist.ac.at
SUMMARY:Laura Cancedda: Targeting aberrant Cl- homeostasis and GABAAergic t
 ransmission  in Down syndrome to design innovative therapeutic approaches
URL:https://talks-calendar.ista.ac.at/events/621
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