Morphological deficits in noradrenergic neurons in GEPR-9s stem from abnormalities in both the locus coeruleus and its target tissues.
The epileptic condition of the genetically epilepsy-prone rat (GEPR) appears to be caused partially by deficiencies in the locus coeruleus (LC) innervation of the superior colliculus (SC). Previous studies provide quantitative documentation of noradrenergic morphological deficits in the moderately epileptic GEPR-3. The present findings extend these studies by applying cell culture methodology to assessments of the severely epileptic GEPR-9. Our data show that total neurite length, the number of neurite branch points per cell, the cross-sectional area of cell bodies, and the cell perimeter are deficient in noradrenergic neurons in LC + SC cocultures derived exclusively from GEPR-9s compared to analogous cocultures obtained solely from nonepileptic control rats. Partial restoration of LC neuron morphology toward normal occurs when the GEPR-9 SC component of the coculture is replaced with nonepileptic control SC. Finally, when the GEPR-9 SC is cocultured with the control LC, a partial morphological deficit occurs in the otherwise normal noradrenergic neurons. However, the magnitude of this deficit is less than that observed in noradrenergic neurons of the GEPR-9 LC cocultured with the control SC. These data support the hypothesis that the developmental deficiencies of noradrenergic neurons of the GEPR-9 are derived from two sources, the LC and its target tissue, in this case, the SC. Also, intrinsic abnormalities of the LC appear to make a more pronounced contribution to the noradrenergic deficits than do those which reside in the SC.
Ryu
J R
JR
College of Pharmacy, Seoul National University, San 56-1, Shillim-dong, Seoul, Kwanak-ku, 151-742, Korea.
Jobe
P C
PC
Milbrandt
J C
JC
Mishra
P K
PK
Clough
R W
RW
Browning
R A
RA
Dailey
J W
JW
Seo
D O
DO
Ko
K H
KH
D000818:Animals; D018920:Coculture Techniques; D046508:Culture Techniques; D004827:Epilepsy / Q000235:genetics / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000002:abnormalities / Q000473:pathology* / Q000648:ultrastructure; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009638:Norepinephrine / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013477:Superior Colliculi / Q000002:abnormalities / Q000473:pathology* / Q000648:ultrastructure
D009638:Norepinephrine