Citation:
J.S. Dunham, J.F.W. Deakin, F. Miyajima, A. Payton, C.T. Toro, Expression of hippocampal brain-derived neurotrophic factor and its receptors in Stanley consortium brains, Journal of Psychiatric Research, Volume 43, Issue 14, September 2009, Pages 1175-1184
Abstract:
Several lines of evidence implicate BDNF in the pathophysiology of psychiatric
illness. BDNF polymorphisms have also been associated with the risk of
schizophrenia and mood disorders. We therefore investigated whether levels of
(pro)BDNF and receptor proteins, TrkB and p75, are altered in hippocampus in
schizophrenia and mood disorder and whether polymorphisms in each gene
influenced protein expression. Formalin-fixed paraffin-embedded hippocampal
sections from subjects with schizophrenia, major depressive disorder (MDD),
bipolar disorder (BPD) and non-psychiatric controls were obtained from the
Stanley Foundation Neuropathology Consortium. (pro)BDNF, TrkB(T1) and p75
protein densities were quantified by immunoautoradiography and DNA extracted
from each subject was used to determine the effect of genotype on protein
expression. In MDD, reductions in (pro)BDNF were seen in all layers of the right
but not the left hippocampus with no changes in the dentate gyrus. The pattern
was similar but less marked for BPD. In addition, BPD but not MDD patients, had
bilateral reductions in p75 in hippocampal layers but not in dentate gyrus. No
changes in TrkB(T1) density were seen in any diagnosis. These findings suggest
MDD and BPD may share impairment in (pro)BDNF expression. However, BPD may
involve impairments of both (pro)BDNF and p75 receptor, whereas MDD may involve
impaired (pro)BDNF alone. Moreover, the lateralisation of changes may indicate a
role of asymmetry in vulnerability to MDD. Hippocampal (pro)BDNF and receptor
levels were also affected by genotype, suggesting that allelic variations are
important in the hippocampal abnormalities seen in these psychiatric disorders.