Neonatal Ethanol Exposure Causes Behavioral Deficits in Young Mice

Xu, Wan; Hawkey, Andrew; Li, Hui; Dai, Lu; Brim, H.; Frank, Jacqueline A.; Luo, Jia; Barron, Susan; Chen, Gang

doi:10.1111/acer.13598

Cited by 16 publications

(10 citation statements)

References 46 publications

(47 reference statements)

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“…The current results agree with clinical [ 44 , 45 ] and animal findings [ 46 , 47 ] that showed deficits in spatial memory in adults associated with neonatal ethanol exposure. However, few studies have emphasized sex differences in memory performance in adult animals exposed to ethanol during perinatal period [ 48 , 49 , 50 , 51 ].…”

Section: Discussionsupporting

confidence: 92%

“…One study, for example, demonstrated that even a single exposure to ethanol in the early postnatal period induced memory impairments in adult male, but not female animals [ 52 ]. Other studies reported that three days of ethanol exposure (PND7–9) induced deficits only in adult male animals [ 48 , 49 ], but longer ethanol exposure (over 5–6 days) promoted memory impairments in both male and female rats [ 47 , 50 , 53 ]. We saw deleterious effect of ethanol on memory in both sexes.…”

Section: Discussionmentioning

confidence: 99%

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Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period

et al. 2021

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Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol during the neonatal period, we investigated the influence of rapamycin, an mTOR Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 1.5 g/kg) using the conditioning place preference (CPP) paradigm. Rapamycin (3 and 10 mg/kg) was given before intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4–9 (an equivalent to the third trimester of human pregnancy). Spatial memory/reversal learning and rewarding ethanol effect were evaluated in adult (PND60–70) rats. Additionally, the impact of rapamycin pre-treatment on the expression of the GluN2B subunit of NMDA receptor in the brain was assessed in adult rats. Our results show that neonatal ethanol exposure induced deficits in spatial memory and reversal learning in adulthood, but the reversal learning outcome may have been due to spatial learning impairments rather than cognitive flexibility impairments. Furthermore, in adulthood the ethanol treated rats were also more sensitive to the rewarding effect of ethanol than the control group. Rapamycin prevented the neonatal effect of ethanol and normalized the GluN2B down-regulation in the hippocampus and the prefrontal cortex, as well as normalized this subunit’s up-regulation in the striatum of adult rats. Our results suggest that rapamycin and related drugs may hold promise as a preventive therapy for fetal alcohol spectrum disorders.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period

et al. 2021

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“…The Morris water maze (MWM) is one of most common behavioral tests of spatial learning for rodents ( Vorhees and Williams, 2006 ). The MWM was performed based on a previously published method with some modifications ( Xu et al, 2018 ). Briefly, each mouse was placed in a round plastic tub with a diameter of 108 cm filled with white-painted water at the temperature of 22–23°C to locate and escape onto a submerged platform.…”

Section: Methodsmentioning

confidence: 99%

Chronic Voluntary Alcohol Drinking Causes Anxiety-like Behavior, Thiamine Deficiency, and Brain Damage of Female Crossed High Alcohol Preferring Mice

Liu

et al. 2021

Front. Pharmacol.

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The central nervous system is vulnerable to chronic alcohol abuse, and alcohol dependence is a chronically relapsing disorder which causes a variety of physical and mental disorders. Appropriate animal models are important for investigating the underlying cellular and molecular mechanisms. The crossed High Alcohol Preferring mice prefer alcohol to water when given free access. In the present study, we used female cHAP mice as a model of chronic voluntary drinking to evaluate the effects of alcohol on neurobehavioral and neuropathological changes. The female cHAP mice had free-choice access to 10% ethanol and water, while control mice had access to water alone at the age of 60-day-old. The mice were exposed to alcohol for 7 months then subjected to neurobehavioral tests including open field (OF), elevated plus maze (EPM), and Morris water maze (MWM). Results from OF and EPM tests suggested that chronic voluntary drinking caused anxiety-like behaviors. After behavior tests, mice were sacrificed, and brain tissues were processed for biochemical analyses. Alcohol altered the levels of several neurotransmitters and neurotrophic factors in the brain including gamma-Aminobutyric acid (GABA), corticotropin-releasing factor, cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor. Alcohol increased the expression of neuroinflammation markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and C-C chemokine receptor 2 (CCR2). Alcohol also induced cleaved caspase-3 and glial fibrillary acidic protein, indicative of neurodegeneration and gliosis. In addition, alcohol inhibited the expression of thiamine transporters in the brain and reduced thiamine levels in the blood. Alcohol also caused oxidative stress and endoplasmic reticulum (ER) stress, and stimulated neurogenesis.

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“…The Morris water maze (MWM) is a test of spatial learning and memory for rodents [ 41 , 42 ]. Animals undergo training and testing sessions include spatial learning, probe trials, reversal learning, and visible cue.…”

Section: Methodsmentioning

confidence: 99%

Thiamine Deficiency Causes Long-Lasting Neurobehavioral Deficits in Mice

Wen

et al. 2020

Brain Sciences

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Thiamine deficiency (TD) has detrimental effects on brain health and neurobehavioral development, and it is associated with many aging-related neurological disorders. To facilitate TD-related neuropsychological studies, we generated a TD mouse model by feeding a thiamine-deficient diet for 30 days, followed by re-feeding the control diet for either one week or 16 weeks as recovery treatment. We then performed neurobehavioral tests in these two cohorts: cohort of one week post TD treatment (1 wk-PTDT) and 16 weeks post TD treatment (16 wks-PTDT). The TD mice showed no significant difference from control in any tests in the 1 wk-PTDT cohort at the age of 13–14 weeks. The tests for the 16 wks-PTDT cohort at the age of 28–29 weeks, however, demonstrated anxiety and reduced locomotion in TD animals in open field and elevated plus maze. In comparison, rotor rod and water maze revealed no differences between TD and control mice. The current findings of the differential effects of the same TD treatment on locomotion and anxiety at different ages may reflect the progressive and moderate change of TD-induced neurobehavioral effects. The study suggests that, even though the immediate neurobehavioral impact of TD is modest or negligible at a young age, the impact could develop and become severe during the aging process.

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Neonatal Ethanol Exposure Causes Behavioral Deficits in Young Mice

Abstract: Based on these data, this neonatal intubation mouse model may be useful for future mechanistic and genetic studies of FASD and for screening of novel therapeutic agents.

Cited by 16 publications

References 46 publications

Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period

Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period

Chronic Voluntary Alcohol Drinking Causes Anxiety-like Behavior, Thiamine Deficiency, and Brain Damage of Female Crossed High Alcohol Preferring Mice

Thiamine Deficiency Causes Long-Lasting Neurobehavioral Deficits in Mice

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