ABSTRACT
Neurons are highly polarized cells with an axon and dendritic arbors. It is still not well studied that how formation and elaboration of axon and dendrites is controlled by diffusible signaling factors such as glutamate via specific receptors. We found that N-methyl-D-aspartate (NMDA) receptors were enriched (stage 2-3) but decreased expression (stage 4-5) at tip of axon of cultured hippocampal neurons during distinct development stages. Inhibition of NMDA receptor activity by competitive antagonist DL-2-amino-5-phosphonovalerate (APV) or channel blocker MK801 promoted axonal outgrowth at the early stages, whereas inhibited dendritic development in later stages. Meanwhile, knockdown of NMDA receptors also promoted axonal outgrowth and branch in immature neurons. Furthermore, GluN2B but not GluN2A subunit inhibited axonal outgrowth in immature hippocampal neurons. Finally, we found that NMDA receptors inhibited axonal outgrowth by inactivating Akt and activating GSK-3ß signaling in a calcineurin-dependent manner. Taken together, our results demonstrate that stabilization GSK-3ß activation in the axon growth cone by Ca2+ influx through NMDA receptors may be involved in regulation of axon formation in immature neurons at early stages.
Subject(s)
Calcineurin/genetics , Glycogen Synthase Kinase 3 beta/genetics , Neuronal Plasticity/genetics , Neurons/metabolism , Proto-Oncogene Proteins c-akt/genetics , Receptors, N-Methyl-D-Aspartate/genetics , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Calcineurin/metabolism , Calcium/metabolism , Cations, Divalent , Dizocilpine Maleate/pharmacology , Embryo, Mammalian , Gene Expression Regulation, Developmental , Glycogen Synthase Kinase 3 beta/metabolism , Hippocampus/drug effects , Hippocampus/embryology , Hippocampus/metabolism , Ion Transport , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Neuronal Plasticity/drug effects , Neurons/cytology , Neurons/drug effects , Primary Cell Culture , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/metabolism , Signal TransductionABSTRACT
OBJECTIVE: To analyze the types of mental disorders caused by traumatic brain injury and the optimal time for forensic psychiatric appraisal. To explore the relationship between the degree of traumatic brain injury, the time of appraisal and the grade of intellectual deficiency. METHODS: Five hundred and thirty-four forensic psychiatric cases of mental disorders caused by traumatic brain injury were retrospectively analyzed. RESULTS: In the types of mental disorders caused by traumatic brain injury, the most cases were diagnosed as organic mood disorders (51.1%), following organic neurosis-like syndrome (24.0%) and organic intellectual deficiency (18.0%). For the disability grades, the most cases were the level VIII and IX disability grades, 219 cases (41.0%) and 177 cases (33.1%), respectively. The degree of brain injury and the degree of intelligence defection according to WAIS-RC were higher in intellectual deficiency group compared with non-intellectual deficiency group (P < 0.05). The grade of disability correlated with the degree of brain injury, the result of WAIS-RC, the result of cerebral CT scanning, and the grade of brain electrical activity mapping (BEAM) abnormality (P < 0.05). Nevertheless, the degree of intellectual deficiency did not correlate with appraisal time and the degree of brain injury (P > 0.05). CONCLUSION: The factors influencing intellectual deficiency are complex. The findings of objective examination including cerebral CT scanning, BEAM, WAIS-RC and others should be considered as important indexes for disability evaluation.
