Adenosine Kinase Expression in the Frontal Cortex in Schizophrenia

Abstract

The adenosine hypothesis of schizophrenia posits that reduced availability of the neuromodulator adenosine contributes to dysregulation of dopamine and glutamate transmission and the symptoms associated with schizophrenia. It has been proposed that increased expression of the enzyme adenosine kinase (ADK) may drive hypofunction of the adenosine system. While animal models of ADK overexpression support such a role for altered ADK, the expression of ADK in schizophrenia has yet to be examined. In this study, we assayed ADK gene and protein expression in frontocortical tissue from schizophrenia subjects. In the dorsolateral prefrontal cortex (DLPFC), ADK-long and -short splice variant expression was not significantly altered in schizophrenia compared to controls. There was also no significant difference in ADK splice variant expression in the frontal cortex of rats treated chronically with haloperidol-decanoate, in a study to identify the effect of antipsychotics on ADK gene expression. ADK protein expression was not significantly altered in the DLPFC or anterior cingulate cortex (ACC). There was no significant effect of antipsychotic medication on ADK protein expression in the DLPFC or ACC. Overall, our results suggest that increased ADK expression does not contribute to hypofunction of the adenosine system in schizophrenia and that alternative mechanisms are involved in dysregulation of this system in schizophrenia.

Gene Enrichment Analysis of Astrocyte Subtypes in Psychiatric Disorders and Psychotropic Medication Datasets

“…The largest changes in astrocyte marker expression are induced by mood stabilizers (lithium and valproate) and the weakest effect is seen in antidepressant datasets. Interestingly, gene expression changes following 4 weeks or 12 weeks of antipsychotic (haloperidol and clozapine) administration differ significantly, as previously observed [ 97 ]. To further explore differences in the chronic effects of antipsychotics on astrocyte-associated gene expression, we assayed the mRNA levels of three established astrocyte markers, GFAP, VIM, and SOX9, in the frontal cortex of rats administered the typical antipsychotic haloperidol-decanoate for 9 months (36 weeks), as this time-point better models a chronic treatment course in schizophrenia patients.…”

Altered purinergic receptor expression in the frontal cortex in schizophrenia

“…Western immunoblot was used to assay P2RX7 and P2RX4 protein expression, as previously described 37 , 38 . Briefly, twenty-five micrograms protein were run on 4–12% Bis-Tris gels (NuPAGE Invitrogen, ThermoFisher Scientific) for 1 h at 180 V. Following semi-dry transfer (18 V, 30 min) and 1 hr blocking (Licor blocking buffer) at room temperature, PVDF membranes were incubated at 4 °C overnight in primary antibody: rabbit anti-P2RX7 (1:1000, APR-004, Alamone), rabbit anti-P2RX4 (1:1000, APR-002, Alamone), goat anti-P2RX7 (1:1000, NBP1–37775, Novus) or a reference protein rabbit anti-valosin containing protein (VCP, 1:1000, ab109240, Abcam), diluted in blocking buffer (Licor) + 0.2% Tween20.…”

The Purinergic System as a Target for the Development of Treatments for Bipolar Disorder

“…− indicates lower levels compared to healthy controls, = indicates equal levels compared to healthy controls, + indicates a subtle increase in levels compared to healthy controls, ++ indicates a moderate increase in levels compared to healthy controls, +++ indicates a high increase in levels compared to healthy controls, DA dopamine, ENT equilibrative nucleoside transporter, MDD major depressive disorder, NT5E ecto-5′-nucleotidase, PNP purine nucleoside phosphorylase, XO xanthine oxidase. Figure created with BioRender.com relevant hypothesis for psychiatric disorders [51][52][53], especially BD and schizophrenia [54][55][56].…”