Effects of chronic hypoxia in developing rats on dendritic morphology of the CA1 subarea of the hippocampus and on fear-potentiated startle.
Chronic hypoxia (CH) present in infants with cyanotic congenital heart disease may be responsible for subsequent cognitive deficits seen in these children. In a rat model of CH [10% O(2) between postnatal day (P) 3 and 28], we have demonstrated significant alterations in energy metabolism and excitatory neurotransmission in the developing hippocampus. These alterations may adversely affect dendritic morphology, which is a highly energy-dependent and excitatory neurotransmitter-mediated event, and hippocampus-mediated behaviors. We measured the apical segment length of dendrites in pyramidal neurons of the CA1 region of the hippocampus using microtubule-associated protein-2 (MAP-2) histochemistry on P28 while the animals were hypoxic (n=8 in CH and n=6 in control), and on P56 after the animals had been normoxic for 4 weeks (n=8/group). We also compared dorsal hippocampus-dependent trace fear conditioning and dorsal hippocampus-independent delay fear conditioning on P56. Developmental trajectory of the apical segment length was similar in CH and controls, decreasing between P28 and P56. However, when compared with the controls, the apical segment length was longer in the CH group on both P28 [55.11+/-2.30 microm (CH) vs. 40.52+/-1.20 microm (control), p<0.001] and P56 [44.01+/-1.56 microm (CH) vs. 31.75+/-1.31 microm (control), p<0.001], suggesting the persistence of an immature dendritic architecture. Both trace and delay fear conditioning were decreased in the CH group, suggesting functional abnormality beyond the dorsal hippocampus. These structural and functional alterations may contribute to the cognitive deficits seen in infants at risk for CH.
Raman
Lakshmi
L
Department of Pediatrics, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN 55415, USA. raman010@umn.edu
Hamilton
Kathryn L
KL
Gewirtz
Jonathan C
JC
Rao
Raghavendra
R
D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D003214:Conditioning, Classical / Q000502:physiology; D003712:Dendrites / Q000473:pathology*; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D017966:Pyramidal Cells / Q000473:pathology* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology*
D008869:Microtubule-Associated Proteins