Is the lack of protein F1/GAP-43 mRNA in granule cells target-dependent?
Protein F1/GAP-43 is differentially expressed in brain with high levels present in regions associated with memory functions. However, in hippocampus the granule cells lack F1/GAP-43 expression. To determine if this lack of expression is due to inhibitory signals from the target cells, we selectively destroyed CA3 pyramidal cells unilaterally using microinjections of excitotoxins. Kainate lesions induced F1/GAP-43 mRNA expression bilaterally in granule cells at 24 h post-injection. Since the induction contralateral to the lesion was not due to loss of target cells, that induction may be ascribed to consequences of seizure activity. However, F1/GAP-43 mRNA hybridization decreased by 3 d post-lesion and was at background levels by 6 d, indicating that the lack of F1/GAP-43 expression in granule cells is restored despite a lack of target neurons. Unilateral lesions of CA3 cells using ibotenate, which are not as complete as kainate but do not cause seizures, did not induce F1/GAP-43 mRNA in granule cells on either the contralateral or, in 4 of 5 cases, the ipsilateral side. Taken together, these data suggest that the CA3 target is not essential for the absence of F1/GAP-43 expression in granule cells. To compare the extent of damage caused by the lesions, we investigated the location of astrocytes undergoing reactive gliosis, employing as a reporter glial fibrillary acidic protein (GFAP) gene expression. After both kainate and ibotenate injections GFAP hybridization increased in the lesioned area as well as in the contralateral hippocampus. These results indicate that injections of kainate, and possibly ibotenate to a lesser extent, may affect behavior not only by damaging cells at the injection site, but also by altering gene expression in cells at distant sites.
Meberg
P J
PJ
Cresap Neuroscience Laboratory, Northwestern University, Evanston, IL 60208, USA.
Jarrard
L E
LE
Routtenberg
A
A
D000818:Animals; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006133:Growth Substances / Q000235:genetics*; D007051:Ibotenic Acid; D007608:Kainic Acid; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D007051:Ibotenic Acid; D007608:Kainic Acid