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Neurotrophic effects of potentiating gaba-mediated dendritic inhibition

Neuropsychopharmacology volume 48, pages 213–214 (2023)Cite this article

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Loss of structures mediating connections between pyramidal cells (PyC), i.e., dendrites and spines, is a hallmark of aging and stress-related disorders, such as depression. These deficits occur in frontal cortex and hippocampus, regions critical for cognition, and are widely accepted as contributing to cognitive deficits. Cognitive deficits in depression and age-related disorders are not treated by current medications, highlighting an unmet need for novel procognitive and neurotrophic therapeutics. Efforts focused on excitatory-, brain-derived neurotrophic factor- or stress-related mechanisms have not yielded breakthroughs. In contrast, despite robust evidence for deficits in aging and depression, GABAergic inhibition has received less attention, since its augmentation impairs cognition without improving cellular connectivity.

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Fig. 1: Dendritic pathology in aging and depression, and reversal by augmented GABAergic inhibition.

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Funding

TP and ES are supported by the Weston Brain Institute, the American Foundation for Suicide Prevention, the Discovery Fund of the Center for Addiction and Mental Health. ES is supported by CIHR. ES and TP are listed inventors on patents covering  the synthesis and use of GABAergic compounds. ES is Founder, acting CEO and CSO of DAMONA Pharmaceuticals, a biopharma dedicated to bringing novel GABAergic compounds to the clinic.

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Authors and Affiliations

  1. Campbell Family Mental Health Research Institute of CAMH, Toronto, ON, M5T 1R8, Canada

    Thomas D. Prevot & Etienne Sibille

  2. Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada

    Thomas D. Prevot & Etienne Sibille

  3. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5T 1R8, Canada

    Etienne Sibille

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  1. Thomas D. Prevot
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  2. Etienne Sibille
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TP and ES wrote the manuscript and prepared the figure.

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Correspondence to Thomas D. Prevot or Etienne Sibille.

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Prevot, T.D., Sibille, E. Neurotrophic effects of potentiating gaba-mediated dendritic inhibition. Neuropsychopharmacol. 48, 213–214 (2023). https://doi.org/10.1038/s41386-022-01423-0

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