Altered expression of neuroplasticity-related genes in the brain of depressed suicides.
BACKGROUND
Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain.


METHODS
Expression levels and coexpression patterns of GPM6A, GPM6B, and PLP1 (two other members of PLP/DM20 family) as well as of the neuroplasticity-related genes identified to associate with GPM6A were determined using quantitative polymerase chain reaction (qPCR) in postmortem samples from the hippocampus (n = 18) and the prefrontal cortex (PFC) (n = 25) of depressed suicide victims and compared with control subjects (hippocampus n = 18; PFC n = 25). Neuroplasticity-related proteins that form complexes with GPM6A were identified by coimmunoprecipitation technique followed by mass spectrometry.


RESULTS
Results indicated transcriptional downregulation of GPM6A and GPM6B in the hippocampus of depressed suicides. The expression level of calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) and coronin1A (CORO1A) was also significantly decreased. Subsequent analysis of coexpression patterns demonstrated coordinated gene expression in the hippocampus and in the PFC indicating that the function of these genes might be coregulated in the human brain. However, in the brain of depressed suicides this coordinated response was disrupted.


CONCLUSIONS
Disruption of coordinated gene expression as well as abnormalities in GPM6A and GPM6B expression and expression of the components of GPM6A complexes were detected in the brain of depressed suicides.
Instituto de Investigaciones Biotecnológicas, CONICET-UNSAM, 1650 San Martin, Argentina. Electronic address: beata@iibintech.com.ar.
B
B
Fuchsova
Instituto de Investigaciones Biotecnológicas, CONICET-UNSAM, 1650 San Martin, Argentina.
A
A
Alvarez Juliá
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
H S
HS
Rizavi
Instituto de Investigaciones Biotecnológicas, CONICET-UNSAM, 1650 San Martin, Argentina.
A C
AC
Frasch
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
G N
GN
Pandey
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism*; D013405:Suicide; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; C484158:GPM6A protein, human; C484160:GPM6B protein, human; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; C472930:PLP1 protein, human; C072061:coronin proteins; C517657:CAMK2A protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
coexpression analysis; glycoprotein M6a; mRNA expression; postmortem; qPCR