title: Cacna1c: Protecting young hippocampal neurons in the adult brain.
abstract: Neuropsychiatric disease is the leading cause of disability in the United States, and fourth worldwide.1,2Not surprisingly, human genetic studies have revealed a common genetic predisposition for many forms of neuropsychiatric disease, potentially explaining why overlapping symptoms are commonly observed across multiple diagnostic categories. For example, theCACNA1Cgene was recently identified in the largest human genome-wide association study to date as a risk loci held in common across 5 major forms of neuropsychiatric disease: bipolar disorder, schizophrenia, major depressive disorder (MDD), autism spectrum disorder and attention deficit-hyperactivity disorder.3This gene encodes for the Cav1.2 subunit of the L-type voltage-gated calcium channel (LTCC), accounting for 85% of LTCCs in the brain, while the Cav1.3 subunit comprises the remainder.4In neurons, LTCCs mediate calcium influx in response to membrane depolarization,5thereby regulating neurotransmission and gene expression. Here, we describe our recent finding that Cav1.2 also controls survival of young hippocampal neurons in the adult brain, which has been linked to the etiology and treatment of neuropsychiatric disease. We also describe the effective restoration of young hippocampal neuron survival in adult Cav1.2 forebrain-specific conditional knockout mice using the neuroprotective compound P7C3-A20.
authors.affiliation: Picower Institute for Learning and Memory, Massachusetts Institute of Technology , Cambridge, MA, USA.
authors.forename: Héctor
authors.initials: H
authors.lastname: De Jesús-Cortés
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics and Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, Cornell University, New York, NY, USA; Weill Cornell Autism Research Program, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Anjali M
authors.initials: AM
authors.lastname: Rajadhyaksha
authors.affiliation: Weill Cornell Autism Research Program, Weill Cornell Medical College, New York, NY, USA; Department of Psychiatry, Department of Neurology, Department of Free Radical and Radiation Biology Program, Department of Radiation Oncology Holden Comprehensive Cancer Center, University of Iowa, Carver College of Medicine, Iowa City, IA, USA; Department of Veteran Affairs, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pieper
keywords: BDNF; Cav; P7C3A20; anxiety; neurogenesis; neuroprotection; P7C3