Alterations in neurotrophin and neurotrophin receptor gene expression patterns in the rat central nervous system following perinatal Borna disease virus infection
M. Zocher et al., Alterations in neurotrophin and neurotrophin receptor gene expression patterns in the rat central nervous system following perinatal Borna disease virus infection, J NEUROVIRO, 6(6), 2000, pp. 462-477
Infection of newborn rats with Borna disease virus (BDV) leads to persisten
ce in the absence of overt signs of inflammation. BDV persistence, however,
causes cerebellar hypoplasia and hippocampal dentate gyrus neuronal cell l
oss, which are accompanied by diverse neurobehavioral abnormalities. Neurot
rophins and their receptors play important roles in the differentiation and
survival of hippocampal and cerebellar neurons. We have examined whether B
DV can cause alterations in the neurotrophin network, thus promoting neuron
al damage. We have used RNase protection assay to measure mRNA levels of th
e neurotrophins nerve growth factor (NGF), brain-derived neurotrophic facto
r (BDNF), and neurotrophin-3 (NT-3), and their trkC and trkB receptors, as
well as the growth factors insulin-like growth factor I (IGF-1) and basic f
ibroblast growth factor (bFGF), in the cerebellum and hippocampus of BDV-in
fected and control rats at different time points p,i, Reduced mRNA expressi
on levels of NT-3, BDNF and NGF were found after day 14 p.i. in the hippoca
mpus, but not in the cerebellum, of newborn infected rats. Three weeks afte
r infection, trkC mRNA expression levels were reduced in both hippocampus a
nd cerebellum of infected rats, whereas decreased trkB mRNA levels were onl
y observed in the cerebellum. Reduced trkC mRNA expression was confined to
the dentate gyrus of the hippocampus, as assessed by in situ hybridization.
TUNEL assay revealed massive apoptotic cell death in the dentate gyrus of
infected rats at days 27 and 33 p,i, Increased numbers of apoptotic cells w
ere also detected in the cerebellar granular layer of infected rats after 8
days p,i. Moreover, a dramatic loss of cerebellar Purkinje cells was seen
after day 27 p,i, Our results support the hypothesis, that BDV-induced alte
rations in neurotrophin systems might contribute to selective neuronal cell
death.