title: Gestational methylazoxymethanol exposure leads to NMDAR dysfunction in hippocampus during early development and lasting deficits in learning.
abstract: The N-methyl-D-aspartate (NMDA) receptor has long been associated with learning and memory processes as well as diseased states, particularly in schizophrenia (SZ). Additionally, SZ is increasingly recognized as a neurodevelopmental disorder with cognitive impairments often preceding the onset of psychosis. However, the cause of these cognitive deficits and what initiates the pathological process is unknown. Growing evidence has implicated the glutamate system and, in particular, N-methyl-D-aspartate receptor (NMDAR) dysfunction in the pathophysiology of SZ. Yet, the vast majority of SZ-related research has focused on NMDAR function in adults leaving the role of NMDARs during development uncharacterized. We used the prenatal methylazoxymethanol acetate (MAM, E17) exposure model to determine the alterations of NMDAR protein levels and function, as well as associated cognitive deficits during development. We found that MAM-exposed animals have significantly altered NMDAR protein levels and function in the juvenile and adolescent hippocampus. Furthermore, these changes are associated with learning and memory deficits in the Morris Water Maze. Thus, in the prenatal MAM-exposure SZ model, NMDAR expression and function is altered during the critical period of hippocampal development. These changes may be involved in disease initiation and cognitive impairment in the early stage of SZ.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Snyder
authors.forename: Alicia E
authors.initials: AE
authors.lastname: Adelman
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Gao
mesh_terms: D000367:Age Factors; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol