Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia.
The neonatal (PND 7) lesion of the ventral hippocampus (VH) with ibotenic acid represents a well-established experimental paradigm that recapitulates many schizophrenia-like phenomena. In order to investigate molecular changes that could contribute to long lasting consequences on brain function, we have investigated the effects of the VH lesion on the expression for the trophic factors FGF-2 and BDNF. We used RNase protection assay to measure their mRNA levels in cortical regions of prepubertal (PND 35) and young adult (PND 56) animals, both under basal condition as well as in response to an acute restraint stress. The expression of BDNF was not altered by the VH lesion in prefrontal (PFC) and frontal cortex (FC) of PND 35 or PND 56 rats. An acute restraint stress at PND 35 produced a significant increase of the neurotrophin expression in PFC of sham as well as lesioned animals. However in young adult animals a significant elevation of BDNF expression was observed only in sham rats. We also found that the VH lesion produced a significant reduction of basal BDNF mRNA levels in the cingulate cortex of young adult, but not prepubertal rats. This effect was not accompanied by changes in the acute modulation of the neurotrophin, which was up-regulated by stress in both experimental groups. Conversely the expression of FGF-2 at PND 35 and PND 56 was not altered by early postnatal VH lesion, and there were no major differences between sham and lesioned animals in response to the acute stress. The changes in trophic factor expression may be relevant for the long-term effects of VH lesion on synaptic plasticity and may determine an increased vulnerability of the brain under challenging situations.
Molteni
R
R
Center for Neuropharmacology, Department of Pharmacological Sciences, University of Milan, Milan, Italy.
Lipska
B K
BK
Weinberger
D R
DR
Racagni
G
G
Riva
M A
MA
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003714:Denervation; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D006179:Gyrus Cinguli / Q000502:physiology; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D007051:Ibotenic Acid; D009473:Neuronal Plasticity / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology*
D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D007051:Ibotenic Acid