Vinpocetine, a PDE1 modulator, regulates markers of cerebral health, inflammation, and oxidative stress in a rat model of prenatal alcohol-induced experimental attention deficit hyperactivity disorder.

Abstract

Prenatal alcohol exposure (PAE) has been shown to induce symptomatology associated with attention deficit hyperactivity disorder (ADHD) by altering neurodevelopmental trajectories. Phosphodiesterase-1 (PDE1) is expressed centrally and has been used in various experimental brain conditions. We investigated the role of vinpocetine, a PDE1 inhibitor, on behavioral phenotypes and important biochemical deficits associated with a PAE rat model of ADHD. Protein markers of cerebral health (synapsin-IIa, BDNF, and pCREB), inflammation (IL-6, IL-10, and TNF-α), and oxidative stress (TBARS, GSH, and SOD) were analyzed in three brain regions (frontal cortex, striatum, and cerebellum). Hyperactivity, inattention, and anxiety introduced in the offspring due to PAE were assayed using open-field, Y-maze, and elevated plus maze, respectively. Administration of vinpocetine (10 & 20 mg/kg, p.o. [by mouth]) to PAE rat offspring for 4 weeks resulted in improvement of the behavioral profile of the animals. Additionally, levels of protein markers such as synapsin-IIa, BDNF, pCREB, IL-10, SOD, and GSH were found to be significantly increased, with a significant reduction in markers such as TNF-α, IL-6, and TBARS in selected brain regions of vinpocetine-treated animals. Vinpocetine, a selective PDE1 inhibitor, rectified behavioral phenotypes associated with ADHD, possibly by improving cerebral function, reducing brain inflammation, and reducing brain oxidative stress. This study provides preliminary analysis and suggests that the PDE1 enzyme may be an important pharmacological tool to study ADHD as a result of PAE.

• Authors: Niti Sharma, Kanishk Luhach, Lalit K Golani, Bhagwat Singh, Bhupesh Sharma
• Journal: Alcohol (Fayetteville, N.Y.) (Alcohol) Vol. 105 Pg. 25-34 (12 2022) ISSN: 1873-6823 [Electronic] United States
• PMID: 35995260 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-10
• Interleukin-6
• Phosphoric Diester Hydrolases
• Tumor Necrosis Factor-alpha
• Ethanol
• vinpocetine
• Vinca Alkaloids

Topics

• Animals
• Female
• Humans
• Pregnancy
• Rats
• Attention Deficit Disorder with Hyperactivity (chemically induced, drug therapy)
• Interleukin-10
• Interleukin-6
• Oxidative Stress
• Phosphoric Diester Hydrolases
• Prenatal Exposure Delayed Effects (chemically induced)
• Tumor Necrosis Factor-alpha
• Ethanol (adverse effects)
• Vinca Alkaloids (pharmacology)