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Detailed DARPP-32 expression profiles in postmortem brains from patients with schizophrenia: an immunohistochemical
Yasuto Kunii1, Keiko Ikemoto, Akira Wada
1Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima, Japan. kunii@fmu.ac.jp
Abstract:
The prevalence of dopamine and cAMP-regulated phosphoprotein 32kD (DARPP-32) is associated with the pathogenesis of schizophrenia. To date, the findings on DARPP-32 cellular expression and distribution in postmortem brains from patients with schizophrenia have been inconsistent. To clarify the detailed cellular expression of DARPP-32 in patients with schizophrenia, we immunohistochemically stained sections from postmortem brains using specific antibodies. We measured the density of immunopositive cells in various brain regions including the prefrontal cortex and compared the data from nine schizophrenia subjects with those of nine age- and sex-matched control subjects. The density of DARPP-32-immunoreactive (IR) neurons was significantly lower in layers II-V of the dorsolateral prefrontal cortex (DLPFC) from subjects with schizophrenia. In contrast, there were no marked differences in DARPP-32 expression in other brain regions. In addition, the density of threonine (Thr34)-phosphorylated DARPP-32-IR neurons was significantly higher in layer V of DLPFC from subjects with schizophrenia. These results suggest that the decrease in DARPP-32 in schizophrenia was more marked in neurons of DLPFC than in other cells or other brain regions, and that this decrease might be partly compensated for by an increase in expression of Thr34-phosphorylated DARPP-32 in DLPFC.
Insights
Schizophrenia patients show reduced dopamine and cAMP-regulated phosphoprotein 32kD (DARPP-32) in the dorsolateral prefrontal cortex (DLPFC). However, increased phosphorylated DARPP-32 in DLPFC layer V may offer partial compensation.
Area of Science:
- Neuroscience
- Molecular Psychiatry
- Cellular Biology
Background:
- Dopamine and cAMP-regulated phosphoprotein 32kD (DARPP-32) is implicated in schizophrenia pathogenesis.
- Previous studies on DARPP-32 expression in schizophrenia brains yielded inconsistent results.
Purpose of the Study:
- To investigate the detailed cellular expression and distribution of DARPP-32 in postmortem brains of schizophrenia patients.
- To clarify inconsistencies in prior research regarding DARPP-32 in schizophrenia.
Main Methods:
- Immunohistochemical staining of postmortem brain sections using specific DARPP-32 antibodies.
- Quantification of DARPP-32-immunoreactive (IR) neuron density in specific brain regions, including the dorsolateral prefrontal cortex (DLPFC).
- Comparison between nine schizophrenia subjects and nine age- and sex-matched controls.
Main Results:
- A significant decrease in DARPP-32-IR neurons was observed in layers II-V of the DLPFC in schizophrenia subjects.
- No significant differences in DARPP-32 expression were found in other brain regions examined.
- A significant increase in threonine (Thr34)-phosphorylated DARPP-32-IR neurons was noted in layer V of the DLPFC in schizophrenia subjects.
Conclusions:
- DARPP-32 reduction in schizophrenia is most pronounced in DLPFC neurons compared to other cells or brain regions.
- Increased Thr34-phosphorylated DARPP-32 in DLPFC may represent a compensatory mechanism in schizophrenia.
