| Objective: To explore the mechanism of early environment on neurobehavioral development by detecting the serum corticosterone, the number of neurons, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in hippocampal CA3 area and frontal lobe of rats.Methods: (1) 45 male SD rats were randomly divided into three groups: the isolated environment, the enriched environment and the control group(n=15). The isolated environment was a monotony cage without any object. The enriched environment was an early intervention with a rich visual environment and touching and hearing. Early intervention of rats was taken from postnatal 24h to 28d. The control group were raised in conventional environment without intervened. (2) The open-field environment test and the Lat maze was performed to assess behavior of the rats. (3)The levels of serum corticosterone of rats were tested by the emission immunology method. (4) The expression of GR/MR and the number of neurons in hippocampus and frontal lobe of rats were examined using immunohistochemistry or Nissl staining. respectivelyResults: (1) In open-field test, the number of passed panels, straightening(times) and grooming(times) in enriched environment group were (11.73±13.81), (2.13±2.44), (3.13±2.00) separately, which were less than those in the control group [(27.67±17.09), (6.20±4.14), (6.47±3.07), P<0.001]. While in the isolated environment group, they were (45.60±22.81), (9.60±5.34), (11.40±3.83) separately which were much more than those in the control group (P<0.001). (2) In the Lat maze, the frequency of running across the corner, straightening (times) and inclining to wall (times) in the enriched environment group were (18.67±19.89), (6.47±9.49), (9.67±8.82) separately, which were less than both in the control group [(34.53±14.11), (16.33±10.22), (17.60±9.47), P<0.001] and the isolated environment group [(52.13±20.76), (26.80±12.63), (27.47±10.08), P<0.001)] (3) The level of serum corticosterone of rats in the enriched environment group was (8.42±3.01 ng/ml), which was lower than that in the control group(11.36±3.92 ng/ml).The level of serum corticosterone in the isolated environment group was (21.74±4.21 ng/ml) which was the highest among three groups(F=52.34, P<0.001). (4) Under the microscope by the Nissl staining, the number of neurons in rat hippocampal CA3 and frontal lobe were (85.76±7.83) and (84.74±7.80)cells/HF seperately in the enriched environment group, which were more than those in the control group (71.18±3.59) and (70.14±3.70)cells/HF. The neural number of CA3 and frontal lobe of the rats in the isolated environment group was (57.60±5.3) and (56.42±5.01)cells/HF which were the least among three groups (F=87.41, P<0.001; F= 90.53, P<0.001). (5) In the immunohistochemistry study, the integrated optical density(IOD) of GR in hippocampal CA3 and frontal lobe of rats in the enriched environment group were (114.96±26.02, 111.96±24.36 ) > in the control group (83.67±8.48, 81.58±8.96) > the isolated environment group (56.16±8.45, 55.02±8.44). F=48.98,P<0.001). And the IOD of MR in hippocampal CA3 and frontal lobe of rats in the enriched environment group were (96.017±27.36, 95.05±27.28), which was higher than that in control group(63.66±8.48, 62.66±8.45) (P<0.01, P<0.001). And both were no significant differences between control group and isolated environment group(66.18±8.44, 65.18±8.44) (P>0.05). (6) There was a positive correlation between the serum corticosterone level and neurobehavior, such as the passed panels, the times of straightening in open-field test, and the frequency of running across the corner, the times of straightening, inclining to wall in the Lat maze (P<0.001). (7) There was a negative correlation between the serum corticosterone level and GR expression in hippocampus and frontal lobe of the rats (P<0.001).Conclusions: (1) Early isolation environment can cause the dysfunction of HPA axis by increasing corticosterone, which will decrease the hippocampal and frontal lobe neurons and increase anxiety, irritability and other abnormal behaviors. (2) The rats can be maintained their serum corticosterone at a lower level in the early enriched and safe environment with less anxiety and irritability, which may imply the early enriched facilitate brain development. (3) The function of HPA axis may be involved in the mechanism about effects of early environment on the unmature brain development and its long-term developmental behavior.
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