Discuss Bipolar
Blog to discuss being Bipolar
Elevated cortical glutamate levels in patients with bipolar disorder are likely to be due to increased glutamate neurotransmission rather than alterations in glutamate metabolism or cycling, say UK researchers.
“If glutamate transmission is indeed elevated in bipolar disorder, it supports the rationale for antiglutamatergic therapies,” they note.
These conclusions are based on the team’s findings of increased vesicular glutamate transporter (VGluT)1 expression in patients with bipolar disorder, compared with mentally healthy individuals and patients with schizophrenia.
“VGluT1 is expressed in glutamatergic neurons, and its expression reflects quantal size and the release of glutamate into the synapse,” Paul Harrison and Sharon Eastwood from the University of Oxford explain.
The researchers used quantitative polymerase chain reaction to measure the anterior cingulate cortex (ACC) gene expression of VGluT1, as well as that of netrin-G1 (isoforms Gqc, G1d, and G1f) and netrin-G2, which are axon guidance and cell adhesion molecules involved in the formation and maintenance of synaptic connections, primarily glutamatergic ones.
Comparisons were made for 34 patients with bipolar disorder, 35 with schizophrenia, and 35 mentally healthy controls.
The findings, published in the journal Biological Psychiatry, showed that expression of VGluT1, netrin-G2, netrin-G1d and, in the right ACC, netrin-G1f were increased in bipolar disorder patients, but not in schizophrenia patients, compared with controls.
“Given the roles of netrin-Gs in the formation and plasticity of excitatory pathways, the finding may contribute to the inferred alteration in glutamate transmission in bipolar disorder or at least be a marker of a shift in the developmental plasticity profile of these pathways,” say Harrison and Eastwood.
In contrast, netrin-G1c was not increased in bipolar disorder or schizophrenia patients, compared with controls.
The researchers say that this finding makes it unlikely that the increases in the other transcripts simply reflect an increased synaptic or neuronal density, “especially since other presynaptic markers and cell counts are either unchanged or reduced in the ACC in bipolar disorder.”
The study findings also showed a robust positive correlation between VGluT1 expression and brain weight, with brain weight explaining about 8% of the variance in VGluT1 expression.
The team speculates that this may “hint at a relationship between activity in glutamatergic circuits and brain growth and that VGluT1 might be one gene contributing to the heritability of brain size.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
No Comments »
No comments yet.
RSS feed for comments on this post. TrackBack URL
Leave a comment
You must be logged in to post a comment.