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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Suicide is a major public health priority, and its molecular mechanisms appear to be related to imbalanced purine metabolism in the brain. This exploratory study investigates purinergic gene expression in the postmortem dorsolateral prefrontal cortex (DLPFC) tissue isolated from subjects with major depressive disorder (MDD) who died by suicide (MDD-S, n = 10), MDD subjects who did not die by suicide (MDD-NS, n = 6) and non-psychiatrically ill controls (CTL, n = 9–10). Purinergic system transcripts were assayed by quantitative polymerase chain reactions (qPCR) in superficial and deep gray matter as well as white matter DLPFC cortical layers using laser microdissection (LMD). Across all subjects, regardless of sex, P2RY12 (F(2,23) = 5.40, p = 0.004) and P2RY13 (KW statistic = 11.82, p = 0.001) transcript levels were significantly greater in MDD-S compared to MDD-NS subjects. Several other perturbations were observed in the white matter tissue isolated from females: NT5E (F(2,10) = 13.37, p = 0.001) and P2RY13 (F(2,9) = 3.99, p = 0.011, controlled for age) transcript expression was significantly greater in MDD-S vs. MDD-NS female groups. ENTPD2 (F(2,10) = 5.20, p = 0.03), ENTPD3 (F(2,10) = 28.99, p < 0.0001), and NT5E (F(2,10) = 13.37, p = 0.001) were among the transcripts whose expression was significantly elevated in MDD-S vs. CTL female groups. Transcripts that exhibited significantly altered expression in the superficial and deep gray matter included ENTPD2, NT5E, PANX1, and P2RY13 (p ≤ 0.05). Our medication analysis revealed that the expression of these transcripts was not significantly altered by antidepressants. This is the first study to holistically quantify the purinergic metabolic pathway transcripts in suicide and MDD utilizing human postmortem brain tissue. Our preliminary findings support evidence implicating changes in purinergic P2 receptors in the brain in suicide and provide support for broader purinergic system dysregulation in mood disorders.

Details

Title
Purinergic System Transcript Changes in the Dorsolateral Prefrontal Cortex in Suicide and Major Depressive Disorder
Author
Sahay, Smita 1   VIAFID ORCID Logo  ; Lundh, Anna E 1 ; Sirole, Roshan P 1 ; McCullumsmith, Robert E 2   VIAFID ORCID Logo  ; Sinead M O’Donovan 3   VIAFID ORCID Logo 

 Department of Neurosciences and Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA; [email protected] (S.S.); 
 Department of Neurosciences and Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA; [email protected] (S.S.); ; Neurosciences Institute, ProMedica, Toledo, OH 43606, USA 
 Department of Neurosciences and Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA; [email protected] (S.S.); ; Department of Biological Sciences, University of Limerick, Castletroy, V94 T9PX Limerick, Ireland 
First page
1826
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3176404464
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.