 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, July 16, 2003, 23(15):6315-6326
Previous Article | Next Article
Gene Expression Deficits in a Subclass of GABA Neurons in the Prefrontal Cortex of Subjects with Schizophrenia
Takanori Hashimoto,1 David W. Volk,2 Stephen M. Eggan,2 Karoly Mirnics,1,3 Joseph N. Pierri,1 Zhuoxin Sun,4 Allan R. Sampson,4 andDavid A. Lewis1,2 Departments of 1Psychiatry, 2Neuroscience, 3Neurobiology, and 4Statistics, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
Markers of inhibitory neurotransmission are altered in the prefrontal cortex (PFC) of subjects with schizophrenia, and several lines of evidence suggest that these alterations may be most prominent in the subset of GABA-containing neurons that express the calcium-binding protein, parvalbumin (PV). To test this hypothesis, we evaluated the expression of mRNAs for PV, another calcium-binding protein, calretinin (CR), and glutamic acid decarboxylase (GAD67) in postmortem brain specimens from 15 pairs of subjects with schizophrenia and matched control subjects using single- and dual-label in situ hybridization. Signal intensity for PV mRNA expression in PFC area 9 was significantly decreased in the subjects with schizophrenia, predominately in layers III and IV. Analysis at the cellular level revealed that this decrease was attributable principally to a reduction in PV mRNA expression per neuron rather than by a decreased density of PV mRNA-positive neurons. In contrast, the same measures of CR mRNA expression were not altered in schizophrenia. These findings were confirmed by findings from cDNA microarray studies using different probes. Across the subjects with schizophrenia, the decrease in neuronal PV mRNA expression was highly associated (r = 0.84) with the decrease in the density of neurons containing detectable levels of GAD67 mRNA. Furthermore, simultaneous detection of PV and GAD67 mRNAs revealed that in subjects with schizophrenia only 55% of PV mRNA-positive neurons had detectable levels of GAD67 mRNA. Given the critical role that PV-containing GABA neurons appear to play in regulating the cognitive functions mediated by the PFC, the selective alterations in gene expression in these neurons may contribute to the cognitive deficits characteristic of schizophrenia.
Key words: calretinin; GABA neurons; GAD67; parvalbumin; prefrontal cortex; schizophrenia
Received Nov. 28, 2002; revised May. 5, 2003; accepted May. 7, 2003.
This article has been cited by other articles:
A. Fisahn, J. Neddens, L. Yan, and A. Buonanno
Neuregulin-1 Modulates Hippocampal Gamma Oscillations: Implications for Schizophrenia
Cereb Cortex, July 16, 2008; (2008) bhn107v1.
[Abstract] [Full Text] [PDF]
S. M. Eggan, T. Hashimoto, and D. A. Lewis
Reduced Cortical Cannabinoid 1 Receptor Messenger RNA and Protein Expression in Schizophrenia
Arch Gen Psychiatry, July 1, 2008; 65(7): 772 - 784.
[Abstract] [Full Text] [PDF]
H. M. Morris, T. Hashimoto, and D. A. Lewis
Alterations in Somatostatin mRNA Expression in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia or Schizoaffective Disorder
Cereb Cortex, July 1, 2008; 18(7): 1575 - 1587.
[Abstract] [Full Text] [PDF]
G. Gonzalez-Burgos and D. A. Lewis
GABA Neurons and the Mechanisms of Network Oscillations: Implications for Understanding Cortical Dysfunction in Schizophrenia
Schizophr Bull, June 26, 2008; (2008) sbn070v1.
[Abstract] [Full Text] [PDF]
U. Meyer, J. Feldon, and B. K. Yee
A Review of the Fetal Brain Cytokine Imbalance Hypothesis of Schizophrenia
Schizophr Bull, April 11, 2008; (2008) sbn022v1.
[Abstract] [Full Text] [PDF]
T. Hashimoto, H. H. Bazmi, K. Mirnics, Q. Wu, A. R. Sampson, and D. A. Lewis
Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects With Schizophrenia
Am J Psychiatry, April 1, 2008; 165(4): 479 - 489.
[Abstract] [Full Text] [PDF]
R. H. Perlis, S. Purcell, J. Fagerness, A. Kirby, T. L. Petryshen, J. Fan, and P. Sklar
Family-Based Association Study of Lithium-Related and Other Candidate Genes in Bipolar Disorder
Arch Gen Psychiatry, January 1, 2008; 65(1): 53 - 61.
[Abstract] [Full Text] [PDF]
N. Gogtay
Cortical Brain Development in Schizophrenia: Insights From Neuroimaging Studies in Childhood-Onset Schizophrenia
Schizophr Bull, January 1, 2008; 34(1): 30 - 36.
[Abstract] [Full Text] [PDF]
M. M. Behrens, S. S. Ali, D. N. Dao, J. Lucero, G. Shekhtman, K. L. Quick, and L. L. Dugan
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
Science, December 7, 2007; 318(5856): 1645 - 1647.
[Abstract] [Full Text] [PDF]
S. M. Sunkin and J. G. Hohmann
Insights from spatially mapped gene expression in the mouse brain
Hum. Mol. Genet., October 15, 2007; 16(R2): R209 - R219.
[Abstract] [Full Text] [PDF]
T. Hikida, H. Jaaro-Peled, S. Seshadri, K. Oishi, C. Hookway, S. Kong, D. Wu, R. Xue, M. Andrade, S. Tankou, et al.
From the Cover: Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans
PNAS, September 4, 2007; 104(36): 14501 - 14506.
[Abstract] [Full Text] [PDF]
J. A. Gray and B. L. Roth
Molecular Targets for Treating Cognitive Dysfunction in Schizophrenia
Schizophr Bull, September 1, 2007; 33(5): 1100 - 1119.
[Abstract] [Full Text] [PDF]
M Medalla, P Lera, M Feinberg, and H Barbas
Specificity in Inhibitory Systems Associated with Prefrontal Pathways to Temporal Cortex in Primates
Cereb Cortex, September 1, 2007; 17(suppl_1): i136 - i150.
[Abstract] [Full Text] [PDF]
W.-J. Gao
Acute Clozapine Suppresses Synchronized Pyramidal Synaptic Network Activity by Increasing Inhibition in the Ferret Prefrontal Cortex
J Neurophysiol, February 1, 2007; 97(2): 1196 - 1208.
[Abstract] [Full Text] [PDF]
G. R. Kuperberg, T. Deckersbach, D. J. Holt, D. Goff, and W. C. West
Increased Temporal and Prefrontal Activity in Response to Semantic Associations in Schizophrenia
Arch Gen Psychiatry, February 1, 2007; 64(2): 138 - 151.
[Abstract] [Full Text] [PDF]
L. Menzies, C. Ooi, S. Kamath, J. Suckling, P. McKenna, P. Fletcher, E. Bullmore, and C. Stephenson
Effects of {gamma}-Aminobutyric Acid-Modulating Drugs on Working Memory and Brain Function in Patients With Schizophrenia
Arch Gen Psychiatry, February 1, 2007; 64(2): 156 - 167.
[Abstract] [Full Text] [PDF]
D. A. Lewis and B. Moghaddam
Cognitive Dysfunction in Schizophrenia: Convergence of {gamma}-Aminobutyric Acid and Glutamate Alterations.
Arch Neurol, October 1, 2006; 63(10): 1372 - 1376.
[Abstract] [Full Text] [PDF]
N.V. Povysheva, G. Gonzalez-Burgos, A.V. Zaitsev, S. Kroner, G. Barrionuevo, D.A. Lewis, and L.S. Krimer
Properties of Excitatory Synaptic Responses in Fast-spiking Interneurons and Pyramidal Cells from Monkey and Rat Prefrontal Cortex
Cereb Cortex, April 1, 2006; 16(4): 541 - 552.
[Abstract] [Full Text] [PDF]
M. O. Cunningham, J. Hunt, S. Middleton, F. E. N. LeBeau, M. G. Gillies, C. H. Davies, P. R. Maycox, M. A. Whittington, and C. Racca
Region-specific reduction in entorhinal gamma oscillations and parvalbumin-immunoreactive neurons in animal models of psychiatric illness.
J. Neurosci., March 8, 2006; 26(10): 2767 - 2776.
[Abstract] [Full Text] [PDF]
T. Hashimoto and D. A. Lewis
BDNF Val66Met Polymorphism and GAD67 mRNA Expression in the Prefrontal Cortex of Subjects With Schizophrenia
Am J Psychiatry, March 1, 2006; 163(3): 534 - 537.
[Abstract] [Full Text] [PDF]
N. H. Woo and B. Lu
Regulation of cortical interneurons by neurotrophins: from development to cognitive disorders.
Neuroscientist, February 1, 2006; 12(1): 43 - 56.
[Abstract] [PDF]
J. W. Kinney, C. N. Davis, I. Tabarean, B. Conti, T. Bartfai, and M. M. Behrens
A Specific Role for NR2A-Containing NMDA Receptors in the Maintenance of Parvalbumin and GAD67 Immunoreactivity in Cultured Interneurons
J. Neurosci., February 1, 2006; 26(5): 1604 - 1615.
[Abstract] [Full Text] [PDF]
S. Akbarian, M. G. Ruehl, E. Bliven, L. A. Luiz, A. C. Peranelli, S. P. Baker, R. C. Roberts, W. E. Bunney Jr, R. C. Conley, E. G. Jones, et al.
Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry, August 1, 2005; 62(8): 829 - 840.
[Abstract] [Full Text] [PDF]
A.V. Zaitsev, G. Gonzalez-Burgos, N.V. Povysheva, S. Kroner, D.A. Lewis, and L.S. Krimer
Localization of Calcium-binding Proteins in Physiologically and Morphologically Characterized Interneurons of Monkey Dorsolateral Prefrontal Cortex
Cereb Cortex, August 1, 2005; 15(8): 1178 - 1186.
[Abstract] [Full Text] [PDF]
D. S.F. Ling and L. S. Benardo
Nootropic Agents Enhance the Recruitment of Fast GABAA Inhibition in Rat Neocortex
Cereb Cortex, July 1, 2005; 15(7): 921 - 928.
[Abstract] [Full Text] [PDF]
N. Pillai-Nair, A. K. Panicker, R. M. Rodriguiz, K. L. Gilmore, G. P. Demyanenko, J. Z. Huang, W. C. Wetsel, and P. F. Maness
Neural Cell Adhesion Molecule-Secreting Transgenic Mice Display Abnormalities in GABAergic Interneurons and Alterations in Behavior
J. Neurosci., May 4, 2005; 25(18): 4659 - 4671.
[Abstract] [Full Text] [PDF]
K. A. Petrie, D. Schmidt, M. Bubser, J. Fadel, R. E. Carraway, and A. Y. Deutch
Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex
J. Neurosci., February 16, 2005; 25(7): 1629 - 1636.
[Abstract] [Full Text] [PDF]
M. Veldic, A. Guidotti, E. Maloku, J. M. Davis, and E. Costa
In psychosis, cortical interneurons overexpress DNA-methyltransferase 1
PNAS, February 8, 2005; 102(6): 2152 - 2157.
[Abstract] [Full Text] [PDF]
J. S. Noh, R. P. Sharma, M. Veldic, A. A. Salvacion, X. Jia, Y. Chen, E. Costa, A. Guidotti, and D. R. Grayson
DNA methyltransferase 1 regulates reelin mRNA expression in mouse primary cortical cultures
PNAS, February 1, 2005; 102(5): 1749 - 1754.
[Abstract] [Full Text] [PDF]
T. Hashimoto, S. E. Bergen, Q. L. Nguyen, B. Xu, L. M. Monteggia, J. N. Pierri, Z. Sun, A. R. Sampson, and D. A. Lewis
Relationship of Brain-Derived Neurotrophic Factor and Its Receptor TrkB to Altered Inhibitory Prefrontal Circuitry in Schizophrenia
J. Neurosci., January 12, 2005; 25(2): 372 - 383.
[Abstract] [Full Text] [PDF]
D. A. LEWIS, D. CRUZ, S. EGGAN, and S. ERICKSON
Postnatal Development of Prefrontal Inhibitory Circuits and the Pathophysiology of Cognitive Dysfunction in Schizophrenia
Ann. N.Y. Acad. Sci., June 1, 2004; 1021(1): 64 - 76.
[Abstract] [Full Text] [PDF]
M. Veldic, H. J. Caruncho, W. S. Liu, J. Davis, R. Satta, D. R. Grayson, A. Guidotti, and E. Costa
DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains
PNAS, January 6, 2004; 101(1): 348 - 353.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|