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Alcohol is one of the most commonly abused drugs, and it impairs diverse functions of the central nervous system, such as cognition and memorization. The dentate gyrus (DG) region of the hippocampus is crucial for spatial memory coding. However, whether alcohol exposure can affect DG neuron activity and impair spatial memory has not been identified. Here, we discovered hippocampus DG as a key region of alcohol exposure damage. (1) We found repeated alcohol exposure overactivated DG neurons, while this activation was not shown in a single alcohol exposure group. (2) Mice exposed to alcohol repeatedly exhibited obvious spatial memory impairment. In summary, our findings provide convincing evidence that the excessive activation of hippocampus neurons is involved in spatial memory impairment caused by repeated alcohol exposure.


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Repeated alcohol exposure induced dentate gyrus related spatial memory damage

Show Author's information Bing-Qian Zhang1,§Tong Zhou1,§Yu-Ting Jiang1,§He Lin2Zhe-Ming Sun2( )Jin-Jun Ding1( )
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
The Third Research Institute of Ministry of Public Security, Shanghai 200031, China

§ Bing-Qian Zhang, Tong Zhou, and Yu-Ting Jiang contributed equally to this work.

Abstract

Alcohol is one of the most commonly abused drugs, and it impairs diverse functions of the central nervous system, such as cognition and memorization. The dentate gyrus (DG) region of the hippocampus is crucial for spatial memory coding. However, whether alcohol exposure can affect DG neuron activity and impair spatial memory has not been identified. Here, we discovered hippocampus DG as a key region of alcohol exposure damage. (1) We found repeated alcohol exposure overactivated DG neurons, while this activation was not shown in a single alcohol exposure group. (2) Mice exposed to alcohol repeatedly exhibited obvious spatial memory impairment. In summary, our findings provide convincing evidence that the excessive activation of hippocampus neurons is involved in spatial memory impairment caused by repeated alcohol exposure.

Keywords: hippocampus, alcohol, spatial memory

References(18)

[1]
Carvalho, A.F., Heilig, M., Perez, A., Probst, C., Rehm, J. Alcohol use disorders. The Lancet, 2019, 394(10200): 781–792.
[2]
Harrison, N. L., Skelly, M. J., Grosserode, E. K., Lowes, D. C., Zeric, T., Phister, S., Salling, M. C. Effects of acute alcohol on excitability in the CNS. Neuropharmacology, 2017, 122: 36–45.
[3]
Yan, T. T., Zhao, Y., Jiang, Z. Y., Chen, J. Y. Acetaldehyde induces cytotoxicity via triggering mitochondrial dysfunction and overactive mitophagy. Molecular Neurobiology, 2022, 59(6): 3933–3946.
[4]
Mira, R. G., Tapia-Rojas, C., Pérez, M. J., Jara, C., Vergara, E. H., Quintanilla, R. A., Cerpa, W. Alcohol impairs hippocampal function: From NMDA receptor synaptic transmission to mitochondrial function. Drug and Alcohol Dependence, 2019, 205: 107628.
[5]
Wirt, R. A., McNeela, A. M., Hyman, J. M. Spatial cognition: Prenatal alcohol exposure and the memory puzzle. Current Biology, 2020, 30(18): R1058–R1061.
[6]
Abrahao, K. P., Salinas, A. G., Lovinger, D. M. Alcohol and the brain: Neuronal molecular targets, synapses, and circuits. Neuron, 2017, 96(6): 1223–1238.
[7]
Lee, D., Balu, K., Zhang, H., Park, H., R., Ro, E. J., Jung, Y.-N., Suh, H. Activity of hippocampal adult-born neurons regulates alcohol withdrawal seizures. JCI insight, 2019, 4(19): e128770.
[8]
Hainmueller, T., Bartos, M. Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories. Nature Reviews Neuroscience, 2020, 21(3): 153–168.
[9]
Salling, M. C., Skelly, M. J., Avegno, E., Regan, S., Zeric, T., Nichols, E., Harrison, N. L. Alcohol consumption during adolescence in a mouse model of binge drinking alters the intrinsic excitability and function of the prefrontal cortex through a reduction in the hyperpolarization-activated cation current. The Journal of neuroscience: the official journal of the Society for Neuroscience, 2018, 38(27): 6207–6222.
[10]
Gallo, F. T., Katche, C., Morici, J. F., Medina, J. H., Weisstaub, N. V. Immediate early genes, memory and psychiatric disorders: Focus on c-fos, Egr1 and arc. Frontiers in Behavioral Neuroscience, 2018, 12: 79.
[11]
Savi, F. F., de Oliveira, A., de Medeiros, G. F., Bozza, F. A., Michels, M., Sharshar, T., Dal-Pizzol, F., Ritter, C. What animal models can tell us about long-term cognitive dysfunction following sepsis: A systematic review. Neuroscience and Biobehavioral Reviews, 2021, 124: 386–404.
[12]
Robinson, N. T. M., Descamps, L. A. L., Russell, L. E., Buchholz, M. O., Bicknell, B. A., Antonov, G. K., Lau, J. Y. N., Nutbrown, R., Schmidt-Hieber, C., Häusser, M. Targeted activation of hippocampal place cells drives memory-guided spatial behavior. Cell, 2020, 183(6): 1586–1599.e10.
[13]
Zhong, S. J., Ding, W. Y., Sun, L., Lu, Y. F., Dong, H., Fan, X. Y., Liu, Z. Y., Chen, R. G., Zhang, S., Ma, Q. et al. Decoding the development of the human hippocampus. Nature, 2020, 577(7791): 531–536.
[14]
Lisman, J., Buzsáki, G., Eichenbaum, H., Nadel, L., Ranganath, C., Redish, A. D. Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nature Neuroscience, 2017, 20(11): 1434–1447.
[15]
Richetin, K., Steullet, P., Pachoud, M., Perbet, R., Parietti, E., Maheswaran, M., Eddarkaoui, S., Bégard, S., Pythoud, C., Rey, M. et al. Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer's disease. Nature Neuroscience, 2020, 23(12): 1567–1579.
[16]
Maher, P., van Leyen, K., Dey, P. N., Honrath, B., Dolga, A., Methner, A. The role of Ca2+ in cell death caused by oxidative glutamate toxicity and ferroptosis. Cell Calcium, 2018, 70: 47–55.
[17]
Plotegher, N., Filadi, R., Pizzo, P., Duchen, M. R. Excitotoxicity revisited: Mitochondria on the verge of a nervous breakdown. Trends in Neurosciences, 2021, 44(5): 342–351.
[18]
Soria, F. N., Pérez-Samartín, A., Martin, A., Gona, K. B., Llop, J., Szczupak, B., Chara, J. C., Matute, C., Domercq, M. Extrasynaptic glutamate release through cystine/glutamate antiporter contributes to ischemic damage. The Journal of Clinical Investigation, 2014, 124(8): 3645–3655.
Publication history
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Publication history

Received: 02 May 2022
Revised: 29 June 2022
Accepted: 06 July 2022
Published: 20 July 2022
Issue date: June 2022

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© The Author(s) 2022

Acknowledgements

We thank Ke Zhang, Ruo-Fan Li, Jie Li, and Han Li for their help during data processing. J.J.D. conceived and designed the study. B.Q.Z. and T.Z. collected the data. Y.T.J. analyzed the data. All of the authors wrote the manuscript together.

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Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attributtion-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission.

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