NDLI: Endogenous Benzodiazepine Site Peptide Ligands Operating Bidirectionally In Vivo in Neurogenesis and Thalamic Oscillations

Content Provider	Springer Nature Link
Author	Möhler, Hanns
Copyright Year	2014
Abstract	By binding to the benzodiazepine site, diazepam binding inhibitor (DBI) is associated with negative allosteric modulation (NAM) of GABA$_{A}$ receptors (Costa and Guidotti in Life Sci 49:325–344, 1991). However, the demonstration of a true physiological role of DBI and its fragments has only recently been reported. Based on DBI gain- and loss-of-function experiments in vivo, DBI and its fragment ODN were found to promote neurogenesis in the subventricular zone in vivo. Acting as NAM on GABA$_{A}$ receptors of precursor cells, DBI counteracted the inhibitory effect of GABA and thereby enhanced the proliferation of these cells (Alfonso et al. in Cell Stem Cell 10:76–87, 2012). Conversely and most remarkably, in similar gain- and loss-of-function experiments in the thalamus, the DBI gene products acted as positive allosteric modulators (PAM) of GABA$_{A}$ receptors in prolonging the duration of IPSCs, an effect which was specific for GABA transmission within the reticular nucleus (nRT) (Christian et al. in Neuron 78:1063–1074, 2013). Since intra-nRT potentiation of GABA transmission by benzodiazepine drugs exerts powerful anti-oscillatory effects, DBI might be endogenously effective by modulating seizure susceptibility. It remains to be seen by which mechanism both NAM and PAM activity can arise from the Dbi gene. Nevertheless, the results open new perspectives on the regionally distinct endogenous modulation of GABA transmission via the benzodiazepine site.
Starting Page	1032
Ending Page	1036
Page Count	5
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	39
Issue Number	6
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2014-04-09
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	GABA$_{A}$ receptors Benzodiazepine receptor Endogenous ligand Neurogenesis Absence epilepsy Neurosciences Neurochemistry Biochemistry Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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