Altered levels of polyamine metabolic genes in various sub-nuclei of the human amygdala in major depressive disorder

Sharma V, Hagenauer MH, Chaudhury S, Thompson RC, Myers RM, Schatzberg AF, Barchas JD, Bunney WE, Akil H, Watson SJ
Society for Neuroscience. 2016.


The dynamic homeostasis of the level of polyamines plays a definitive role in regulating structure and functions of the cell. Due to the polycationic nature of these molecules, they play an important role in the cell growth, proliferation, transcription, translation, repair of extracellular matrix and cell signaling processes. Increased levels of polyamines cause detrimental effects to the cell by induction of apoptosis and cell transformation. The altered expression of genes responsible for synthesis and/ degradation of polyamines have been linked to the neurodegeneration of cells in different regions in the brain resulting in pathophysiology of various psychiatric conditions like schizophrenia, bipolar disorder and major depressive disorder. Major depressive disorder (MDD) patients present with diverse yet debilitating symptoms implicating dysfunction of multiple brain regions of which the amygdala is an important regulatory center. The amygdala plays an important role in emotion, motivation and other higher cognitive functions that contribute to the subjective value to the stimulus. However, still there is a scant knowledge describing the effects of altered levels of expression of polyamine metabolic genes in the human amygdala particularly in MDD. Additionally, the human amygdala is a heterogeneous structure comprising of numerous sub-nuclei that vary in size and shape throughout the anterior-posterior axis. We used laser capture microdissection (LCM) to dissect the nuclei from the human amygdala precisely 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). To assess the changes in the levels of polyamine metabolic genes in various sub-nuclei of human amygdala, postmortem human brain of normal healthy and MDD subjects were used for LCM based microarray gene expression analysis and qRT-PCR. Preliminary results from microarray data show differentially the altered level of polyamine metabolic genes in various sub-nuclei of human amygdala. The results are discussed in light of the function of various sub-nuclei of human amygdala, which 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.!/4071/presentation/22034