Neonatal exposure to MK801 induces structural reorganization of the central nervous system.
Schizophrenia, a progressive disorder displaying widespread pathological changes, is associated with the loss of glutamatergic function and selective loss of cytoskeletal proteins, such as MAP2, in regions severely affected by this disease. As schizophrenia is associated with perinatal brain trauma, we monitored changes in several functionally different proteins following injury-promoting MK801 blockade of N-methyl-D-aspartate receptors in neonatal rats. Within the somatosensory cortex, MK801 triggered robust, caspase-3-dependent apoptotic injury, reduced expression of cytoskeletal proteins MAP2 and tau, and increased synapse associated protein SNAP25. Thus, both neuronal injury and loss of structural elements important for successful cell-cell contact may reorganize brain circuitry, which at later ages could promote similar behavioral changes observed in schizophrenia.
Lema Tomé
Carla M
CM
Department of Neurobiology and Anatomy, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157, USA.
Nottingham
Charles U
CU
Smith
Chelsey M
CM
Beauchamp
Amanda S
AS
Leung
Parkson W
PW
Turner
Christopher P
CP
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000009:adverse effects; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects; D018698:Glutamic Acid / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000187:drug effects* / Q000378:metabolism; D009415:Nerve Net / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D050825:Synaptosomal-Associated Protein 25 / Q000187:drug effects / Q000378:metabolism; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D050825:Synaptosomal-Associated Protein 25; D016875:tau Proteins; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases