Iron chelation decreases BDNF expression in human neuroblastoma cells.

<p><b>A.</b> SH-SY5Y cells were treated with either vehicle or 100 µM deferoxamine (DFO) for 24 hours. RT-PCR measures of BDNF transcripts show a decrease in total BDNF transcripts (tBDNF, variants 1–14, 16–18 (*p<0.01, n = 4–5). <b>B.</b> Iron chelation did not cause changes in cell survival as assessed by trypan blue exclusion 24 hours post-treatment (n = 5). <b>C.</b> SH-SY5Y cells were transfected with luciferase reporters for the promoter regions of BDNF I–IV and were then treated with 100 µM deferoxamine for 24 hours. No significant differences were observed between control and treated cells (n = 3–4).</p

CpKO mice have decreased concentrations of iron in the cerebral cortex and striatum.

<p>Atomic absorption measures of cortical and striatal biopsy punches show significant decreases in iron concentrations in CpKO compared to wild type mice in both the cerebral cortex ( n = 18; *p<0.02) and the striatum (n = 7; *p<0.03).</p

The expression of BDNF is reduced in the cerebral cortex and striatum of ceruloplasmin-deficient mice.

<p><b>A.</b> RT-PCR measures of the 4 BDNF transcripts show a decrease in BDNF transcripts 1, 2 and 4 in the cortex of the CpKO mouse (*p<0.04, n = 5). <b>B.</b> RT-PCR measures of the 4 BDNF transcripts show a decrease in BDNF transcripts 1, 2, 3 and 4 in the striatum of the CpKO mouse (*p<0.05, n = 5). <b>C.</b> Examples of immunoblots of BDNF protein levels in the cortex and striatum (top panel) and densitometry results showing significant decreases BDNF protein levels (normalized to actin level) using Image J software. (*p<0.03; n = 4 WT and 3 CpKO mice).</p

CpKO mice have increased cerebral infarct volume after focal ischemic stroke.

<p><b>A.</b> Representative images of TTC-stained brain sections in mice subjected to 45 min MCAO with a 72 hours post-stroke survival. <b>B.</b> Calculation of percent infarct volume show a significant increase in the cortex and hemisphere of the CpKO mice compared to WT mice. (*p<0.002; n = 8 WT and 6 KO mice).</p