AKAP protein alterations implicated in bipolar disorder

By Lucy Piper, Senior medwireNews Reporter

Researchers have found increased cellular expression of the postsynaptic signaling protein AKAP5/79 in the anterior cingulate cortex (ACC) of patients with bipolar disorder (BD).

Their results, published in the Journal of Psychiatric Research, show both an increased density of neurons expressing the protein in the ACC and more pronounced immunostaining of intraneuronal AKAP.

These findings fit with recent reports of elevated glutamatergic neurotransmission and plasticity of the ACC in patients with BD, say the researchers, led by Hans-Gert Bernstein, from the University of Magdeburg in Germany.

"It seems conceivable that more extensive dysregulation of the interaction between glutamatergic and monoaminergic neurotransmission might occur in BD, and that altered expression of AKAP5 as an integrator of glutamatergic and monoaminergic signalling cascades might be a signature of such a dysregulation," they explain.

Immunohistochemical and morphometric techniques were used to investigate the cellular expression of AKAP5/79 in stored brain tissue samples from 10 deceased people who had BD and 10 who were mentally healthy.

In the patients with BD, the numerical density of AKAP-5-expressing neurons was significantly increased in the left and right ACC, compared with in controls, but not in the dorsolateral prefrontal cortex.

Also, cell counting of different layers showed that AKAP5-positive cell densities were significantly increased in left-side layers II, III, and IV, and right-side layers III, IV, and V of the ACC in BD patients.

The researchers note that, as cortical thickness and total neuronal densities were similar for patients and controls, this increase is unlikely to result from tissue shrinkage or other brain morphologic alterations.

"Our results further suggest that this elevated AKAP expression is not the consequence of the chronic administration of antidepressants or lithium," they add.

It was not only AKAP5 expression that was altered in patients with BD, but also the vast majority of identified binding/reaction partners of the protein. These were either up-regulated (eg, cAMP-dependent protein kinase A and GTPAse activating protein 1) or down-regulated (eg, NMDA-type glutamate receptor 2B and beta-adrenergic receptor).

"AKAP and its interaction partners might thus be potential targets for therapeutic interventions in the treatment of BD," the researchers conclude.

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