Schizophrenia and sex associated differences in the expression of neuronal and oligodendrocyte-specific genes in individual thalamic nuclei.
Considerable evidence based on the study of postmortem brain tissue suggests deficits in both neuronal and myelin systems in schizophrenia (SZ). To date, the majority of the biochemical and molecular biological studies have focused on the cerebral cortex. Most information traveling to or from the cortex is relayed or synaptically gated through the thalamus, and numerous studies suggest structural and functional abnormalities in interconnected regions of the thalamus and cortex in SZ. The present study extends our gene expression studies of neuronal and myelin systems to the thalamus. Quantitative PCR was employed to assess the expression of 10 genes in 5 divisions of the thalamus which were precisely harvested using Laser Capture Microdissection. The divisions studied were present on coronal sections at the level of the centromedian nucleus (CMN) taken from 14 schizophrenic and 16 normal control postmortem brains. The genes examined were specific for oligodendrocytes (MAG, CNP, MBP), neurons (ENO2), glutamatergic neurons (VGlut1, VGlut2, PV, CB) or GABAergic neurons (GAD65, GAD67). Expression levels for each of these markers were quantitated and compared between diagnoses, between sexes, and across nuclei. CB was much more highly expressed in the CMN in SZs compared to NCs. No other diagnosis related differences in gene expression were observed. The expression levels of CNP and MAG, but not MBP, were highly correlated with one another and both, but not MBP, were much more highly expressed in females than in males in all thalamic divisions examined. All markers were differentially expressed across nuclei.
Byne
William
W
Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, United States.
Dracheva
Stella
S
Chin
Benjamin
B
Schmeidler
James M
JM
Davis
Kenneth L
KL
Haroutunian
Vahram
V
D000368:Aged; D064026:Calbindins; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020646:Intralaminar Thalamic Nuclei / Q000378:metabolism; D008297:Male; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011569:Psychiatric Status Rating Scales; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D012737:Sex Factors; D013787:Thalamic Nuclei / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism
D064026:Calbindins; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D064030:S100 Calcium Binding Protein G; C493476:SLC17A6 protein, human; D050599:Vesicular Glutamate Transport Protein 2; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2