Aperçu: G.M.
Les
canaux de calcium de type L (CTRL) Cav1.2 et Cav1.3, codés par les
gènes CACNA1C et CACNA1D, respectivement, sont des régulateurs
importants de l'afflux de calcium dans les cellules et sont essentiels
au développement normal du cerveau et à la plasticité. Chez
les humains, CACNA1C est apparu comme l'un des gènes de risque
candidats les plus avancés et les plus avancés pour une gamme de
troubles neuropsychiatriques, y compris le trouble bipolaire (BD), la
schizophrénie (SCZ), le trouble dépressif majeur, le trouble du spectre
de l'autisme et le trouble déficitaire de l'attention et hyperactivité .
Neurotherapeutics. 2017 May 11. doi: 10.1007/s13311-017-0532-0.
From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms
Kabir ZD1,2, Martínez-Rivera A1,2, Rajadhyaksha AM3,4,5.
Author information
- 1
- Pediatric Neurology, Pediatrics, Weill Cornell Medicine, New York, NY, USA.
- 2
- Weill Cornell Autism Research Program, Weill Cornell Medicine, New York, NY, USA.
- 3
- Pediatric Neurology, Pediatrics, Weill Cornell Medicine, New York, NY, USA. amr2011@med.cornell.edu
- 4
- Weill Cornell Autism Research Program, Weill Cornell Medicine, New York, NY, USA. amr2011@med.cornell.edu.
- 5
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. amr2011@med.cornell.edu.
Abstract
The L-type calcium channels (LTCCs) Cav1.2 and Cav1.3,
encoded by the CACNA1C and CACNA1D genes, respectively, are important
regulators of calcium influx into cells and are critical for normal
brain development and plasticity. In humans, CACNA1C has emerged as one
of the most widely reproduced and prominent candidate risk genes for a
range of neuropsychiatric disorders, including bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder, autism spectrum disorder, and attention deficit hyperactivity disorder. Separately, CACNA1D has been found to be associated with BD and autism spectrum disorder,
as well as cocaine dependence, a comorbid feature associated with
psychiatric disorders. Despite growing evidence of a significant link
between CACNA1C and CACNA1D and psychiatric disorders, our understanding
of the biological mechanisms by which these LTCCs mediate
neuropsychiatric-associated endophenotypes, many of which are shared
across the different disorders, remains rudimentary. Clinical studies
with LTCC blockers testing their efficacy to alleviate symptoms
associated with BD, SCZ, and drug dependence have provided mixed
results, underscoring the importance of further exploring the
neurobiological consequences of dysregulated Cav1.2 and Cav1.3.
Here, we provide a review of clinical studies that have evaluated LTCC
blockers for BD, SCZ, and drug dependence-associated symptoms, as well
as rodent studies that have identified Cav1.2- and Cav1.3-specific
molecular and cellular cascades that underlie mood (anxiety,
depression), social behavior, cognition, and addiction.
- PMID: 28497380
- DOI: 10.1007/s13311-017-0532-0
