Polyamine metabolic enzyme gene expression analysis of human amygdala of major depressive disorder samples

Sharma V, Hagenauer M, Chaudhury S, Thompson RC, Myers RM, Schatzberg AF, Barchas JD, Bunney WE, Akil H, Watson SJ
Society of Neuroscience. 2015.


The polyamine pathways are important in cell growth as well as proliferation and are activated (or regulated) by G-proteins, protein kinases, nucleotide cyclases and receptors. Few recent studies have focused on the role of polyamines and their metabolic enzymes in the etiology and pathology of mental disorders. Altered levels of mRNA of polyamine enzymes arginase II (ARG2), S-adenosylmethionine decarboxylase (AMD1), and antizymes 1 and 2 (OAZ1 and OAZ2) have been observed in conditions like schizophrenia, major depressive disorder and bipolar disorder. The amygdala plays an important role in emotion, motivation and other higher cognitive functions which result in the addition of the subjective value to the stimulus. It appears to act as a neural gateway for binding the sensory representations with the neural correlates of emotional and motivational valence, thereby linking sensory information to adaptive responses and meaningful experiences. Because the human amygdala is a heterogeneous structure containing numerous nuclei that vary in size and shape through the anterior-posterior axis, we utilized laser capture microdissection to precisely dissect the nuclei from the human amygdala into ten divisions (Lateral (L), Basal (B), Accessory Basal (AB), Central (CE), Medial (M), Cortical (CO), Periamygdaloid Cortex (PAC), Amygdalohippocampal Area (AHA), Anterior Amygdaloid Area (AAA) and Paralaminar (PL) nuclei) followed by microarray gene expression analysis. Microarray data revealed the altered levels of the above said genes in the different sub-nuclei of amygdala which prompted us to further investigate the genes for polyamine metabolism. Thus, in the present study we assess the levels of gene expression of polyamine metabolic enzymes in various amygdala subnuclei of postmortem human brain of normal healthy and major depressive disorder subjects. The findings will help us in understanding the role of polyamines and their metabolic enzymes in the functioning of human amygdalar sub-nuclei in major depressive disorder.