Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions
Adolescence is a developmental period that encompasses, but is not limited to, puberty and continues into early adulthood. During this period, maturation and refinement are observed across brain regions such as the prefrontal cortex (PFC), which is critical for cognitive function. Adolescence is als...
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MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/19/3111 |
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| author | Christopher Douglas Walker Hannah Gray Sexton Jentre Hyde Brittani Greene Mary-Louise Risher |
| author_facet | Christopher Douglas Walker Hannah Gray Sexton Jentre Hyde Brittani Greene Mary-Louise Risher |
| author_sort | Christopher Douglas Walker |
| collection | DOAJ |
| description | Adolescence is a developmental period that encompasses, but is not limited to, puberty and continues into early adulthood. During this period, maturation and refinement are observed across brain regions such as the prefrontal cortex (PFC), which is critical for cognitive function. Adolescence is also a time when excessive alcohol consumption in the form of binge drinking peaks, increasing the risk of long-term cognitive deficits and the risk of developing an alcohol use disorder later in life. Animal models have revealed that adolescent ethanol (EtOH) exposure results in protracted disruption of neuronal function and performance on PFC-dependent tasks that require higher-order decision-making. However, the role of astrocytes in EtOH-induced disruption of prefrontal cortex-dependent function has yet to be elucidated. Astrocytes have complex morphologies with an extensive network of peripheral astrocyte processes (PAPs) that ensheathe pre- and postsynaptic terminals to form the ‘tripartite synapse.’ At the tripartite synapse, astrocytes play several critical roles, including synaptic maintenance, dendritic spine maturation, and neurotransmitter clearance through proximity-dependent interactions. Here, we investigate the effects of adolescent binge EtOH exposure on astrocyte morphology, PAP-synaptic proximity, synaptic stabilization proteins, and dendritic spine morphology in subregions of the PFC that are important in the emergence of higher cognitive function. We found that adolescent binge EtOH exposure resulted in subregion specific changes in astrocyte morphology and astrocyte-neuronal interactions. While this did not correspond to a loss of astrocytes, synapses, or dendritic spines, there was a corresponding region-specific and EtOH-dependent shift in dendritic spine phenotype. Lastly, we found that changes in astrocyte-neuronal interactions were not a consequence of changes in the expression of key synaptic structural proteins neurexin, neuroligin 1, or neuroligin 3. These data demonstrate that adolescent EtOH exposure results in enduring effects on neuron-glia interactions that persist into adulthood in a subregion-specific PFC manner, suggesting selective vulnerability. Further work is necessary to understand the functional and behavioral implications. |
| first_indexed | 2024-03-09T21:53:17Z |
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| language | English |
| last_indexed | 2024-03-09T21:53:17Z |
| publishDate | 2022-10-01 |
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| series | Cells |
| spelling | doaj.art-e80ef576651c472abbf8554c15aa72032023-11-23T20:02:59ZengMDPI AGCells2073-44092022-10-011119311110.3390/cells11193111Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex SubregionsChristopher Douglas Walker0Hannah Gray Sexton1Jentre Hyde2Brittani Greene3Mary-Louise Risher4Department of Biomedical Research, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USADepartment of Biomedical Research, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USADepartment of Biomedical Research, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USADepartment of Biomedical Research, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USADepartment of Biomedical Research, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USAAdolescence is a developmental period that encompasses, but is not limited to, puberty and continues into early adulthood. During this period, maturation and refinement are observed across brain regions such as the prefrontal cortex (PFC), which is critical for cognitive function. Adolescence is also a time when excessive alcohol consumption in the form of binge drinking peaks, increasing the risk of long-term cognitive deficits and the risk of developing an alcohol use disorder later in life. Animal models have revealed that adolescent ethanol (EtOH) exposure results in protracted disruption of neuronal function and performance on PFC-dependent tasks that require higher-order decision-making. However, the role of astrocytes in EtOH-induced disruption of prefrontal cortex-dependent function has yet to be elucidated. Astrocytes have complex morphologies with an extensive network of peripheral astrocyte processes (PAPs) that ensheathe pre- and postsynaptic terminals to form the ‘tripartite synapse.’ At the tripartite synapse, astrocytes play several critical roles, including synaptic maintenance, dendritic spine maturation, and neurotransmitter clearance through proximity-dependent interactions. Here, we investigate the effects of adolescent binge EtOH exposure on astrocyte morphology, PAP-synaptic proximity, synaptic stabilization proteins, and dendritic spine morphology in subregions of the PFC that are important in the emergence of higher cognitive function. We found that adolescent binge EtOH exposure resulted in subregion specific changes in astrocyte morphology and astrocyte-neuronal interactions. While this did not correspond to a loss of astrocytes, synapses, or dendritic spines, there was a corresponding region-specific and EtOH-dependent shift in dendritic spine phenotype. Lastly, we found that changes in astrocyte-neuronal interactions were not a consequence of changes in the expression of key synaptic structural proteins neurexin, neuroligin 1, or neuroligin 3. These data demonstrate that adolescent EtOH exposure results in enduring effects on neuron-glia interactions that persist into adulthood in a subregion-specific PFC manner, suggesting selective vulnerability. Further work is necessary to understand the functional and behavioral implications.https://www.mdpi.com/2073-4409/11/19/3111astrocyteadolescentethanolprefrontal cortextripartite synapse |
| spellingShingle | Christopher Douglas Walker Hannah Gray Sexton Jentre Hyde Brittani Greene Mary-Louise Risher Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions Cells astrocyte adolescent ethanol prefrontal cortex tripartite synapse |
| title | Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions |
| title_full | Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions |
| title_fullStr | Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions |
| title_full_unstemmed | Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions |
| title_short | Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions |
| title_sort | diverging effects of adolescent ethanol exposure on tripartite synaptic development across prefrontal cortex subregions |
| topic | astrocyte adolescent ethanol prefrontal cortex tripartite synapse |
| url | https://www.mdpi.com/2073-4409/11/19/3111 |
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