A new treatment for cognitive disorders related to in utero exposure to alcohol★

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Abstract

Maternal alcohol consumption during pregnancy has detrimental effects on fetal central nervous system development. Maternal alcohol consumption prior to and during pregnancy significantly affects cognitive functions in offspring, which may be related to changes in cyclin-dependent kinase 5 because it is associated with modulation of synaptic plasticity and impaired learning and memory. In this study, we examined adult offspring in a maternal alcohol consumption model in rats. Y-maze test results showed that in utero exposure to alcohol impairs learning and memory capacities. Cyclin-dependent kinase 5 mRNA and protein expressions in the hippocampus of the offspring were significantly elevated, as assayed by quantitative real-time PCR and reverse transcription-PCR, immunofluorescence, and immuno-precipitation. Our experimental findings strongly suggest that altered cyclin-dependent kinase 5 may mediate impaired learning and memory in adult rats that were exposed to alcohol by maternal consumption while in utero.

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Most cited references 57

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Synaptic plasticity: multiple forms, functions, and mechanisms.

Ami Citri, Robert Malenka (2008)

Experiences, whether they be learning in a classroom, a stressful event, or ingestion of a psychoactive substance, impact the brain by modifying the activity and organization of specific neural circuitry. A major mechanism by which the neural activity generated by an experience modifies brain function is via modifications of synaptic transmission; that is, synaptic plasticity. Here, we review current understanding of the mechanisms of the major forms of synaptic plasticity at excitatory synapses in the mammalian brain. We also provide examples of the possible developmental and behavioral functions of synaptic plasticity and how maladaptive synaptic plasticity may contribute to neuropsychiatric disorders.

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Learning induces long-term potentiation in the hippocampus.

Jonathan Whitlock, Arnold Heynen, Marshall G Hussain Shuler … (2006)

Years of intensive investigation have yielded a sophisticated understanding of long-term potentiation (LTP) induced in hippocampal area CA1 by high-frequency stimulation (HFS). These efforts have been motivated by the belief that similar synaptic modifications occur during memory formation, but it has never been shown that learning actually induces LTP in CA1. We found that one-trial inhibitory avoidance learning in rats produced the same changes in hippocampal glutamate receptors as induction of LTP with HFS and caused a spatially restricted increase in the amplitude of evoked synaptic transmission in CA1 in vivo. Because the learning-induced synaptic potentiation occluded HFS-induced LTP, we conclude that inhibitory avoidance training induces LTP in CA1.

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Long-term potentiation and memory.

M A Lynch (2004)

One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP.

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Author and article information

Journal

Journal ID (nlm-ta): Neural Regen Res

Journal ID (iso-abbrev): Neural Regen Res

Journal ID (publisher-id): NRR

Title: Neural Regeneration Research

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 1673-5374

ISSN (Electronic): 1876-7958

Publication date (Print): 25 June 2013

Volume: 8

Issue: 18

Pages: 1702-1713

Affiliations

[1 ] Second Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, Henan Province, China

[2 ] Department of Physiology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China

[3 ] First Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, Henan Province, China

[4 ] Department of Immunology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China

[5 ] Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453003, Henan Province, China

[6 ] School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan Province, China

Author notes

Corresponding author: Ruiling Zhang, Professor, Chief phycisian, Second Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, Henan Province; Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453003, Henan Province, China, zhangruilingxx@ 123456163.com . (N20120116003)

Author contributions: Shuang Li conducted the experiments and wrote the manuscript. Yan Zhang conducted the data analysis and statistical processing. Ruiling Zhang provided the research support. Wei Hao and Wancai Yang provided experimental guidance. Feng Zhu, Bin Zhang, Jianying Lin, and Chunyang Xu conducted the animal experiments. All authors approved the final version of the manuscript.

Author statements: The manuscript is original, has not been submitted to or is not under consideration by another publication, has not been previously published in any language or any form, including electronic, and contains no disclosure of confidential information or authorship/patent application/funding source disputations.

Article

Publisher ID: NRR-8-1702

DOI: 10.3969/j.issn.1673-5374.2013.18.008

PMC ID: 4145914

SO-VID: 30c2a808-0439-469c-867e-09bac9734281

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A new treatment for cognitive disorders related to in utero exposure to alcohol★

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UN Sustainable Development Goals on ScienceOpen

Most cited references 57

Synaptic plasticity: multiple forms, functions, and mechanisms.

Learning induces long-term potentiation in the hippocampus.

Long-term potentiation and memory.

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