Cited by 192Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersEpilepsy research and treatment

Modulation of GABAergic transmission in development and neurodevelopmental disorders: investigating physiology and pathology to gain therapeutic perspectives

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Deidda, Gabriele, Bozarth, Ignacio F., Cancedda, Laura·2014·Frontiers in Cellular Neuroscience

Abstract

During mammalian ontogenesis, the neurotransmitter GABA is a fundamental regulator of neuronal networks. In neuronal development, GABAergic signaling regulates neural proliferation, migration, differentiation, and neuronal-network wiring. In the adult, GABA orchestrates the activity of different neuronal cell-types largely interconnected, by powerfully modulating synaptic activity. GABA exerts these functions by binding to chloride-permeable ionotropic GABAA receptors and metabotropic GABAB receptors. According to its functional importance during development, GABA is implicated in a number of neurodevelopmental disorders such as autism, Fragile X, Rett syndrome, Down syndrome, schizophrenia, Tourette's syndrome and neurofibromatosis. The strength and polarity of GABAergic transmission is continuously modulated during physiological, but also pathological conditions. For GABAergic transmission through GABAA receptors, strength regulation is achieved by different mechanisms such as modulation of GABAA receptors themselves, variation of intracellular chloride concentration, and alteration in GABA metabolism. In the never-ending effort to find possible treatments for GABA-related neurological diseases, of great importance would be modulating GABAergic transmission in a safe and possibly physiological way, without the dangers of either silencing network activity or causing epileptic seizures. In this review, we will discuss the different ways to modulate GABAergic transmission normally at work both during physiological and pathological conditions. Our aim is to highlight new research perspectives for therapeutic treatments that reinstate natural and physiological brain functions in neuro-pathological conditions.

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Authors
Deidda, G., Bozarth, I. F., & Cancedda, L.
Affiliations
Italian Institute of Technology (IT)
Corresponding author
Cancedda, Laura
Venue
Frontiers in Cellular Neuroscience
Published
2014-05-22
Volume
8
Pages
119-119
ISSN
1662-5102 (ISSN-L)
OpenAlex
W2104834189
Cited by
192
References
359
Citations by year
2026: 8 · 2025: 14 · 2024: 16 · 2023: 19 · 2022: 23 · 2021: 18 · 2020: 21 · 2019: 9 · 2018: 12 · 2017: 11 · 2016: 15 · 2015: 18 · 2014: 7
FWCI
1.94
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
Compagnia di San Paolo
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
Keywords
GABAergic neurotransmission, GABAA receptor, GABAB receptors, neurodevelopmental disorders, neuronal development, synaptic modulation, intracellular chloride, GABA metabolism, autism spectrum disorder, fragile X syndrome, Rett syndrome, Down syndrome, schizophrenia, Tourette syndrome, neurofibromatosis, epilepsy, therapeutic target

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