Chronic Intermittent Ethanol Exposure Alters Behavioral Flexibility in Aged Rats Compared to Adult Rats and Modifies Protein and Protein Pathways Related to Alzheimer's Disease.
Chronic Intermittent Ethanol Exposure Alters Behavioral Flexibility in Aged Rats Compared to Adult Rats and Modifies Protein and Protein Pathways Related to Alzheimer's Disease.
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DOI：
10.1021/acsomega.2c04528
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发表时间：
2022-12-20
期刊：
影响因子：
4.1
通讯作者：
Matthews, Douglas B.
中科院分区：
文献类型：
--
作者：
Ho, Ada Man-Choi;Peyton, Mina P.;Scaletty, Samantha J.;Trapp, Sarah;Schreiber, Areonna;Madden, Benjamin J.;Choi, Doo-Sup;Matthews, Douglas B.
反复过量饮酒会增加患认知能力下降和痴呆症的风险。老年人中的危险饮酒进一步增加了这种脆弱性。为了研究酒精是否会导致老年人的认知障碍，我们对8周龄的年轻成年大鼠和70周龄的老年大鼠进行了慢性间歇性酒精暴露范式(每隔一天灌胃乙醇或水10次)。在Morris水迷宫中，两个年龄组的大鼠在第5和第10次灌胃后，在Morris水迷宫中的空间记忆恢复没有显著差异，但在老年组中，乙醇处理的大鼠的行为灵活性比水处理的大鼠受到了损害，而在青年组中则没有。然后，我们研究了乙醇处理相关的海马蛋白质组和磷蛋白质组在老年大鼠中的明显差异。我们鉴定了几个与乙醇处理相关的蛋白质，包括PRKCD蛋白水平的上调，它的几个磷酸位点，以及它的激酶活性和Camk2a蛋白水平的下调。我们的生物信息学分析揭示了神经传递调节、突触可塑性、神经元凋亡和胰岛素受体信号转导等通路的显著变化。总而言之，我们的行为和蛋白质组学结果确定了几个可能与酒精导致老年人认知能力下降有关的候选蛋白质和途径。
Repeated excessive alcohol consumption increases the risk of developing cognitive decline and dementia. Hazardous drinking among older adults further increases such vulnerabilities. To investigate whether alcohol induces cognitive deficits in older adults, we performed a chronic intermittent ethanol exposure paradigm (ethanol or water gavage every other day 10 times) in 8-week-old young adult and 70-week-old aged rats. While spatial memory retrieval ascertained by probe trials in the Morris water maze was not significantly different between ethanol-treated and water-treated rats in both age groups after the fifth and tenth gavages, behavioral flexibility was impaired in ethanol-treated rats compared to water-treated rats in the aged group but not in the young adult group. We then examined ethanol-treatment-associated hippocampal proteomic and phosphoproteomic differences distinct in the aged rats. We identified several ethanol-treatment-related proteins, including the upregulations of the Prkcd protein level, several of its phosphosites, and its kinase activity and downregulation in the Camk2a protein level. Our bioinformatic analysis revealed notable changes in pathways involved in neurotransmission regulation, synaptic plasticity, neuronal apoptosis, and insulin receptor signaling. In conclusion, our behavioral and proteomic results identified several candidate proteins and pathways potentially associated with alcohol-induced cognitive decline in aged adults.
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DOI：
10.1111/add.15292
发表时间：
2021-06
期刊：
Addiction (Abingdon, England)
影响因子：
--
作者：
Calvo E;Allel K;Staudinger UM;Castillo-Carniglia A;Medina JT;Keyes KM
通讯作者：
Keyes KM
胰岛素与阿尔茨海默氏病和衰老的认知下降和萎缩有不同的关系。
DOI：
10.1016/j.bbadis.2011.06.011
发表时间：
2012-03
影响因子：
6.2
作者：
Burns, Jeffrey M.;Honea, Robyn A.;Vidoni, Eric D.;Hutfles, Lewis J.;Brooks, William M.;Swerdlow, Russell H.
通讯作者：
Swerdlow, Russell H.
影响因子：
3.6
作者：
Ghosh A;Giese KP
通讯作者：
Giese KP
影响因子：
2.9
作者：
de Oliveira DF;de Lemos RR;de Oliveira JR
通讯作者：
de Oliveira JR
影响因子：
3.6
作者：
Coleman, Leon Garland, Jr.;Liu, Wen;Oguz, Ipek;Styner, Martin;Crews, Fulton T.
通讯作者：
Crews, Fulton T.