Differential effect of serum from bipolar versus schizophrenic patients on spontaneous acetylcholine release at mammalian neuromuscular junction

Abstract

Objective: The diagnosis of bipolar disease frequently requires a long time since the age of onset, especially because the disease ismisdiagnosed with schizophrenia. The aim of the present work was to investigate whether sera from bipolar patients have an activesubstance that allows making a fast identification of the disease.Methods: Sera from healthy volunteers, euthymic and non-stabilized bipolar patients, and schizophrenic patients were passively transferredinto CF1 mice and after 2 day injections, MEPP frequency from diaphragm muscles was recorded. The same procedure was performedwith sera fraction of high and low MW (cut-off 3000).Results: Sera from non-stabilized bipolar patients induced a decreased MEPP frequency and occluded the presynaptic inhibitory effect ofthe specific adenosine A1 receptor agonist 2-chloro-N6-cyclopentyl-adenosine (CCPA) in the recipient mice, while in the euthymic bipolargroup spontaneous secretion reached control values although the action of CCPA was still prevented. Similar results were obtained withlow MW sera fraction from euthymic and non-stabilized bipolar patients. The addition of adenosine deaminase to the sera fraction preventedthe modification of spontaneous ACh release. In mice injected with sera from schizophrenic patients, MEPP frequency was withincontrol values and CCPA induced its typical inhibitory action.Conclusions: These results indicate that bipolar patients contain in their blood an active substance compatible with adenosine, which wasable to modify spontaneous ACh release in the recipient mice. This effect was not observed with sera from healthy volunteers and schizophrenicpatients. The increase of adenosine concentration may result from synaptic hyperactivity that presumably plays a role in thesymptoms of bipolar disorder and/or may derive from peripheral cells through a more general mechanism.Significance: The different results obtained with bipolar and schizophrenic sera raise the possibility that the passive transfer model couldbe used as a diagnostic test in the future.