Alterations of BDNF, mGluR5, Homer1a, p11 and excitatory/inhibitory balance in corticolimbic brain regions of suicide decedents

Abstract

Background: Developing biological based approaches for preventing suicide has become a priority. In recent years, there has been a surge in studies investigating the role of the glutamatergic system in suicide, although it remains unclear.

Methods: We evaluated changes in the gene expression of the metabotropic glutamate receptor 5 (mGluR5) and its scaffolding proteins Homer1a and p11 in the dorsolateral prefrontal cortex (DLPFC), amygdala (AMY), and hippocampus (HIP) of 28 suicide decedents (S) (with no clinical psychiatric history or treatment with anxiolytics or antidepressants) and 26 controls (C) by real-time PCR (qPCR). Indeed, we measured BDNF gene expression and VGluT1 and VGAT immunoreactivities in the HIP by qPCR and immunohistochemistry, respectively. Cases and controls matched for age (C: 48.6 ± 11.6 years; S: 46.9 ± 14.5 years) and postmortem interval (PMI; C: 20.1 ± 13h; S: 16.9 ± 5h).

Results: In DLPFC, S had lower p11 gene expression levels, but no differences were found in mGluR5 or Homer1a. In the AMY and HIP, mGluR5 and Homer1a were increased, p11 and BDNF were reduced. In the HIP, there were less VGAT-ir and more VGluT1-ir.

Limitations: Future studies are necessary to evaluate protein levels, and determine the cell types and potential compensatory mechanisms in a larger sample including S diagnosed with psychiatric disorders, females and different ethnicities.

Conclusions: This study identified significant alterations in mGluR5, Homer1a, p11, BDNF and excitatory/inhibitory balance in corticolimbic brain areas of S. These results further characterize the biological basis of suicide, contributing to the identification of potential biomarkers for suicide prevention.

Keywords: Amygdala; BDNF; Dorsolateral prefrontal cortex; Homer1a; Suicide; VGAT; VGluT1; hippocampus; mGluR5; p11.