QBI Neuroscience Seminar: The right thing at the wrong time is the wrong thing': The ups and downs of Prozac
Event Details
- Date:
- Friday, 01 February 2013
- Time:
- 12:00 pm
- Room:
- Auditorium, Level 7
- UQ Location:
- Queensland Brain Institute (St Lucia)
- URL:
- http://www.tifr.res.in/~dbs/faculty/V_Vaidya.html
- Event category(s):
Event Contact
- Name:
- Mr Reeza Nazer
- Phone:
- 66353
- Email:
- r.nazer@uq.edu.au
- Org. Unit:
- Queensland Brain Institute
Event Description
- Full Description:
- Speaker:Associate Professor Vidita Vaidya
Department of Biological Sciences, The Tata institute of Fundamental Research
Title: The right thing at the wrong time is the wrong thing': The ups and downs of Prozac
Abstract: Postnatal fluoxetine evokes anxiogenic and depressive behavior, whereas adult fluoxetine
administration is anxiolytic and antidepressant. The mechanistic underpinnings of this paradox are
poorly understood. We have examined persistent behavioral perturbations following postnatal
fluoxetine (PNFlx) and underlying molecular changes within the hippocampus, a structure implicated
in the modulation of mood. PNFlx-evoked behaviors emerge early and are long-lasting, with
decreased juvenile play and increased anxiety across life. Our transcriptome analyses indicate
dysregulated gene expression in PNFLx animals, with functional enrichment of genes involved in key
signaling pathways. We noted specific transcripts (Hdac4, mTOR, Gnai1, Prkcc, Hcn1) that were
consistently dysregulated across life, and selectively influenced by postnatal, but not adult,
fluoxetine. Enhanced HDAC4 recruitment at the promoters of select signaling genes like mTOR and
Gnai1 implicate HDAC4 in the dysregulation of specific genes following PNFlx. The emergence of
anxiety and the Hdac4 and mTOR dysregulation was prevented by co-administration of a histone
deacetylase inhibitor sodium butyrate along with PNFlx treatment. Importantly, we also find that re-
treatment of PNFlx animals with fluoxetine in adulthood reversed the increased Hdac4 expression,
prevented HDAC4 recruitment to mTOR and Gnai1 promoters, attenuated the decline in mTOR and
Gnai1 expression, coincident with a normalization of PNFlx-evoked anxiety. Finally we show that
viral overexpression of HDAC4 in the hippocampus evokes specific behavioral changes. Our results
highlight the unique nature of molecular signatures evoked by PNFlx, and implicate HDAC4
dysregulation in the emergence of perturbed emotionality following fluoxetine treatment in early life.
Directions to UQ
- Google Map:
-
- Directions:
- St Lucia Campus | Gatton campus.
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