[Expression of P75NTR protein and RhoA mRNA in the brain of neonatal rats with white matter damage].
OBJECTIVE
Recent studies have indicated that the signal pathway of NgR-P75NTR- RhoA plays a key role in nerve injury and remodeling, but its exact mechanism and the role of the downstream molecule RhoA regulated by P75NTR remain unclear in hypoxia-ischemia (HI) neonatal animals. The present study was designed to assess the expression of P75NTR protein and RhoA mRNA in neonatal white matter and to investigate their relationship in newborn rats with white matter damage (WMD).


METHODS
The rat WMD model was established by the ligation of right common carotid artery, followed by 6% hypoxia exposure for 4 hrs. The control group was sham-operated, without HI treatment. The histological changes of brain tissue were observed under light and electron microscopes. Expression of P75NTR protein and RhoA mRNA in the brain white matter after 12, 24, 48 and 72 hrs and 7 days of HI were detected by RT-PCR and immunohistochemistry, respectively.


RESULTS
Periventricular white matter damage was observed by 48 hrs of HI. Expression of P75NTR protein increased in the striatum and callosum zones at 12 hrs, peaked at 48 hrs, and remained at a higher level than control until 72 hrs of HI in the WMD group (P < 0.01). After 7 days of HI expression of P75NTR protein was no longer statistically different from controls. The RhoA mRNA was higher in the WMD group for the first 72 hrs and then declined to control values.


CONCLUSIONS
Increased P75NTR protein might mediate apoptosis of nerve cells and inhibit the regeneration of neuron axons. The subsequent decline back to control value may be correlated with the aggregation of necrosis of nerve cells after HI. The patterns of RhoA mRNA expression were consistent with those of P75NTR protein, suggesting that the increased P75NTR level may promote RhoA mRNA expression.
Li
De-Yuan
DY
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Chen
Juan
J
Shi
Jing
J
Li
Jin-Hui
JH
Yao
Yu-Jia
YJ
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D020742:rhoA GTP-Binding Protein