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Published on: August 5, 2017
Early ethanol exposure and vinpocetine treatment alter learning- and memory-related proteins in the rat hippocampus
Patricia C Swart1, Christopher B Currin1, Vivienne A Russell1
1Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, 7925, South Africa.
Insights
Early ethanol exposure alters brain signaling pathways, specifically the phosphorylated extracellular signal-related kinase (P-ERK) pathway in the prefrontal cortex and dorsal hippocampus, even without causing behavioral deficits. Vinpocetine treatment did not reverse these neural changes.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Early-life exposure to ethanol can have lasting effects on brain development and function.
- Neural plasticity, crucial for learning and memory, may be particularly vulnerable during critical developmental periods.
- Understanding the molecular mechanisms underlying these effects is essential for developing potential interventions.
Purpose of the Study:
- To investigate the long-term effects of early ethanol exposure on cognitive function and neural plasticity-related proteins in the rat brain.
- To determine if vinpocetine, a phosphodiesterase type 1 inhibitor, can reverse ethanol-induced changes.
- To examine the impact on the phosphorylated extracellular signal-related kinase (P-ERK) signaling pathway in specific brain regions.
Main Methods:
- Sprague-Dawley rats were exposed to ethanol or saline from postnatal days 4-9.
- Behavioral testing (open field, Morris water maze) was conducted from postnatal days 25-31.
- Vinpocetine or vehicle was administered to ethanol-exposed rats during the testing phase.
- Levels of P-ERK and other neural plasticity proteins were analyzed in the prefrontal cortex (PFC) and dorsal hippocampus (DH).
Main Results:
- Ethanol exposure did not impair spatial memory in the Morris water maze.
- A significant ethanol-induced alteration in the P-ERK/ERK ratio was observed in the PFC (decreased) and DH (increased).
- Vinpocetine treatment did not reverse behavioral deficits but induced changes in neural plasticity proteins, including mitogen-activated protein kinase phosphatase, brain-derived neurotrophic factor, phosphorylated-glycogen synthase kinase β, and synaptophysin.
Conclusions:
- Early ethanol exposure can induce molecular changes in neural plasticity pathways without overt behavioral deficits.
- Vinpocetine's interaction with ethanol-exposed brains warrants further investigation, as it alters specific protein expressions.
- This study highlights the complex long-term neurobiological consequences of early-life alcohol exposure.
Abstract:
This study investigates the effects of early exposure to ethanol on cognitive function and neural plasticity-related proteins in the rat brain. Sprague-Dawley rats were administered 12% ethanol solution (4 g/kg/day i.p.) or saline from P4 to P9. Vinpocetine, a phosphodiesterase type 1 inhibitor, was tested to determine whether it could reverse any changes induced by early ethanol exposure. Hence, from P25 to P31, ethanol-exposed male rats were injected with vinpocetine (20 mg/kg/day i.p.) or vehicle (DMSO) prior to undergoing behavioral testing in the open field and Morris water maze (MWM) tests. Ethanol exposure did not adversely affect spatial memory in the MWM. A key finding in this study was a significant ethanol-induced change in the function of the phosphorylated extracellular signal-related kinase (P-ERK) signaling pathway in the prefrontal cortex (PFC) and dorsal hippocampus (DH) of rats that did not display overt behavioral deficits. The P-ERK/ERK ratio was decreased in the PFC and increased in the DH of ethanol-exposed rats compared with controls. Rats that received vinpocetine in addition to ethanol did not display any behavioral changes but did show alterations in neural plasticity-related proteins. Mitogen-activated protein kinase phosphatase was increased, whereas brain-derived neurotrophic factor was decreased, in the PFC of vinpocetine-treated ethanol-exposed rats, and phosphorylated-glycogen synthase kinase β and synaptophysin were increased in the DH of these rats. This study provides insight into the long-term effects of early ethanol exposure and its interaction with vinpocetine in the rat brain. © 2016 Wiley Periodicals, Inc.
