scholarly journals The neurochemical pathology of schizophrenia: post-mortem studies from dopamine to parvalbumin

Author(s):  
Gavin P. Reynolds

AbstractResearch in Peter Riederer’s lab in Vienna in the late 1970’s came from a strong tradition in post-mortem neurochemical studies, at that time a relatively niche approach in neuroscience research. He was also early to recognise the value of post-mortem brain tissue in elucidating pharmacological mechanisms of neuropsychiatric treatments. I was fortunate to have Peter Riederer as a mentor in my early post-doctoral career; his generous support and the opportunities to use post-mortem brain tissue provided an invaluable grounding on which much of my future research was based. In this paper, I shall provide a brief overview of one trajectory of my research into the neurobiology of schizophrenia that started in the Riederer lab in Vienna investigating dopamine and the D2 receptor. Subsequent research to understand findings of increased dopamine resulted in the identification of reduced GABAergic innervation, culminating in the finding of a deficit in the parvalbumin-containing subtype of GABAergic neurons. Most recent work has been studying how changes in DNA methylation of the parvalbumin gene may relate to these findings in psychotic illness and its animal models.

2016 ◽  
Vol 12 ◽  
pp. P462-P462
Author(s):  
Martina M. Hughes ◽  
Beatriz G. Perez-Nievas ◽  
Claire Troakes ◽  
Michael Perkinton ◽  
Diane P. Hanger ◽  
...  

2018 ◽  
Vol 12 ◽  
Author(s):  
Simin Mahinrad ◽  
Marjolein Bulk ◽  
Isabelle van der Velpen ◽  
Ahmed Mahfouz ◽  
Willeke van Roon-Mom ◽  
...  

2019 ◽  
Vol 20 (14) ◽  
pp. 3600 ◽  
Author(s):  
Víctor Fernández-Dueñas ◽  
Maricel Gómez-Soler ◽  
Marta Valle-León ◽  
Masahiko Watanabe ◽  
Isidre Ferrer ◽  
...  

Background: Several biophysical techniques have been successfully implemented to detect G protein-coupled receptors (GPCRs) heteromerization. Although these approaches have made it possible to ascertain the presence of GPCR heteromers in animal models of disease, no success has been accomplished in pathological human post-mortem brains. The AlphaScreen technology has been consistently used to quantify small analyte accumulation or depletion, bimolecular interactions, and post-translational modifications. The high signal-to-background, dynamic range and sensitivity exhibited by this technology support that it may be suitable to detect GPCR heteromers even under non-optimal conditions. Methods: Here, we describe the development of a new AlphaScreen assay to detect GPCR oligomers in human post-mortem brain. Results: Adenosine A2A-dopamine D2 receptor (A2AR/D2R) heteromer formation was monitored in caudate from healthy and Parkinson’s disease (PD) subjects. The approach was first validated using striatal membranes from wild type and A2AR deficient mice. Secondly, we took advantage of the 6-hydroxydopamine hemiparkinsonian rat model to validate previous results. In addition, finally, A2AR/D2R heteromer formation was assessed in caudate membranes from human post-mortem brains. Importantly, our preliminary results revealed an increase in A2AR/D2R heteromer formation in PD brains. Conclusions: The new AlphaScreen assay allowed assessing GPCR heteromers in human post-mortem brains with high sensitivity.


2008 ◽  
Vol 9 (3) ◽  
pp. 181-194 ◽  
Author(s):  
Isidre Ferrer ◽  
Anna Martinez ◽  
Susana Boluda ◽  
Piero Parchi ◽  
Marta Barrachina

2010 ◽  
Vol 16 (8) ◽  
pp. 836-847 ◽  
Author(s):  
C Conejero-Goldberg ◽  
T M Hyde ◽  
S Chen ◽  
U Dreses-Werringloer ◽  
M M Herman ◽  
...  

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