Influence Of Transient Hypoxia On The Expression Of NeuroD And Its Role In The Delayed Brain Neurogenesis

Objective To observe the influence of transient hypoxia on the expression of NeuroD in rat brain and investigate its possible roles in neural regeneration.Methods To investigate the influence of transient hypoxia on the expression of NeuroD, asphyxia was induced in rat pups by performing a delayed cesarean section on pregnant Sprague-Dawley rats.The expression of NeuroD was measured by RT-PCR and immunofluorescence. To investigate the role of NeuroD in neural regeneration, the delayed cesarean section was performed on pregnant SD rats and the newborn rats were returned to dams. In vitro, influence of transient hypoxia on the expression of NeuroD was analyzed on the outcome of embryonic rat neurons in culture. The expression of NeuroD was measured by RT-PCR and the cell proliferation was measured by incorporation of BrdU. In vivo, neurobehavioral consequences of the hypoxic episode were evaluated by using standard behavioral tests for psychomotor and coordination performances and learning capacities.The expression of NeuroD was monitored at the level of DG and CA1 layer of the hippocampus by in situ hybridization.Results NeuroD mRNA increased after the exposure to hypoxia ( P < 0.05 ).Compared with the control group, NeuroD showed no much difference at cerebral cortex but increased significantly at nucleus caudatus putamen detected by immunofluorescence. As revealed by neurobehavioral consequences, hypoxia did not impair psychomotor or learning capacities but improved memory retrieval scores. In vitro, following hypoxia for 3 hours in cultured neurons, NeuroD increased distinctly and with incorporation of BrdU revealed an accumulation of proliferating cells. Following hypoxia in vivo induced higher expression of NeuroD in DG and CA1 subfield of the hippocampus at days 13,20,27 post hypoxia and significantly at P20. Conclusions First, the expression of NeuroD was increased the exposure to hypoxia. Second, the expression of NeuroD was increased post asphyxia in cultured neurons, following with cell proliferation. Third, the differential expression of NeuroD coincided with the dalyed brain neurogenesis. As mentioned above, NeuroD seems to play a role in the process of neurogenesis.