Animal models for studies of alcohol effects on the trajectory of age-related cognitive decline

Foster, Thomas C.

doi:10.1016/j.alcohol.2022.04.005

Cited by 6 publications

(6 citation statements)

References 109 publications

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“…Future research is needed to better understand the impact of CIEg during adolescence on cognitive performance in female subjects. In addition, research is needed to understand the effect of CIEg during adolescence on episodic type tasks in the water maze [i.e., spatial working memory tasks ( Foster, 2023 )].…”

Section: Discussionmentioning

confidence: 99%

Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life

Matthews,

Scaletty,

Trapp

et al. 2023

Front. Behav. Neurosci.

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Binge-like ethanol exposure during adolescence has been shown to produce long lasting effects in animal models including anxiety-like behavior that can last into young adulthood and impairments in cognition that can last throughout most of the lifespan. However, little research has investigated if binge-like ethanol exposure during adolescence produces persistent anxiety-like behavior and concomitantly impairs cognition late in life. Furthermore, few studies have investigated such behavioral effects in both female and male rats over the lifespan. Finally, it is yet to be determined if binge-like ethanol exposure during adolescence alters microglia activation in relevant brain regions late in life. In the present study female and male adolescent rats were exposed to either 3.0 or 5.0 g/kg ethanol, or water control, in a chronic intermittent pattern before being tested in the elevated plus maze and open field task over the next ∼18 months. Animals were then trained in a spatial reference task via the Morris water maze before having their behavioral flexibility tested. Finally, brains were removed, sectioned and presumptive microglia activation determined using autoradiography for [3H]PK11195 binding. Males, but not females, displayed an anxiety-like phenotype initially following the chronic intermittent ethanol exposure paradigm which resolved in adulthood. Further, males but not females had altered spatial reference learning and impaired behavioral flexibility late in life. Conversely, [3H]PK11195 binding was significantly elevated in females compared to males late in life and the level of microglia activation interacted as a function of sex and brain regions, but there was no long-term outcome related to adolescent alcohol exposure. These data further confirm that binge-like ethanol exposure during adolescence produces alterations in behavior that can last throughout the lifespan. In addition, the data suggest that microglia activation late in life is not exacerbated by prior binge-like ethanol exposure during adolescence but the expression is sex- and brain region-dependent across the lifespan.

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Section: Discussionmentioning

confidence: 99%

Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life

Matthews,

Scaletty,

Trapp

et al. 2023

Front. Behav. Neurosci.

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show abstract

“…Impaired behavioral flexibility has been found in both young adult rats − and aged rats , following chronic ethanol exposure in adolescence. Due to well-known cognitive deficits in aged animals, it seems likely that CIEE in aged animals will also produce deficits in behavioral flexibility in aged animals. Behavioral flexibility has been argued to be a form of episodic memory in rats and provides a behavioral tool to assess the impact of chronic ethanol and aging on cognitive function.…”

Section: Introductionmentioning

confidence: 99%

“…Due to well-known cognitive deficits in aged animals, it seems likely that CIEE in aged animals will also produce deficits in behavioral flexibility in aged animals. Behavioral flexibility has been argued to be a form of episodic memory in rats and provides a behavioral tool to assess the impact of chronic ethanol and aging on cognitive function. Recently, it has been shown that chronic ethanol consumption is a predictive factor in the development of dementia including Alzheimer’s disease (AD) .…”

Section: Introductionmentioning

confidence: 99%

“…One critical brain region for reversal learning is the hippocampus, as it has been demonstrated that blocking hippocampal LTD impairs reversal learning performance in the Morris water maze and that reversal learning increases the functional connectivity between the hippocampus and other brain regions in mice . Furthermore, lesions of either the perforant path or the fimbria/fornix (prominent hippocampal afferents) impair reversal learning in rodents. , Given the involvement of the hippocampus in behavioral flexibility and the well-documented impairments in hippocampal function produced by ethanol and normal biological aging, it is important to understand how CIEE in aged animals alters the hippocampal proteome.…”

Section: Introductionmentioning

confidence: 99%

“… 36 Furthermore, lesions of either the perforant path or the fimbria/fornix (prominent hippocampal afferents) impair reversal learning in rodents. 37 , 38 Given the involvement of the hippocampus in behavioral flexibility and the well-documented impairments in hippocampal function produced by ethanol 23 and normal biological aging, 32 it is important to understand how CIEE in aged animals alters the hippocampal proteome.…”

Section: Introductionmentioning

confidence: 99%

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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

Peyton

Scaletty

et al. 2022

ACS Omega

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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 8week-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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On the critical need to investigate the effect of alcohol in the older population

Matthews

Koob

2023

Alcohol

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Animal models for studies of alcohol effects on the trajectory of age-related cognitive decline

Cited by 6 publications

References 109 publications

Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life

Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life

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

On the critical need to investigate the effect of alcohol in the older population

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