Yarema B. Bezchlibnyk, Jun-Feng Wang,

Glenda M. MacQueen, L. Trevor Young

McMasters University



Previous investigation has implicated a number of biochemical

pathways and genetic targets in the etiology of mood disorders.  To expand

on this work, and identify expression differences between BD and MDD subjects

and controls, we used cDNA expression arrays containing up to 1,200 genes. 

This investigation was undertaken in frontal cortex, post-mortem brain tissue

from the Stanley Foundation Neuropathology Consortium, pooled according to

DSM-IV diagnoses of bipolar disorder (BD), and matched controls (n=10 each).

Results include expression differences (>35% change in signal intensity)

between controls and BD or MDD in a number of genes (n=24, n=38

respectively).  7 of these (n=5 from BD, 2 from MDD arrays) were selected

for further analysis, including TGF-b1, procaspase-8, TOB, decorin, HIAP-2,

ERK-5, and PLC-1.  Pooled samples were then analysed by RT-PCR, which

confirmed differential expression of TGF-betal, TOB and pre-procaspase-8 in BD,

and HIAP-2 in MDD.  We further confirmed a significant (p=0.045) decrease

of TGF-betal mRNA levels in BD, and a trend (p=0.055) towards decreased

TGF-betal levels in MDD by RT-PCR in individual subjects.  Studies are

currently underway to examine the effect of chronic lithium treatment in rats on

the level of TGF-betal mRNA by Northern hybridization.  Male Sprague-Dawley

rats were divided into control and lithium treated groups, and sacrificed after

2 hours, 1 day, or 14 days (n=6 for each group) after the start of

treatment.  Each group was given intraperitoneal injections once daily,

with saline or lithium chloride (127 mg/kg).  In addition, we are

endeavoring to confirm these results in protein by immunoblotting and

ELISA.  Given the neuroprotective role accrued to this inhibitory cytokine,

our results suggest that the downregulation of TGF-betal may lead to various

neurotoxic insults potentially involved in the etiology of certain mood