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Status Public on Nov 06, 2025
Title Alcohol Dependence-Induced Astrocyte Immune Activation in the Nucleus Accumbens
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Astrocytes play many physiological roles in the brain including maintenance of brain homeostasis, modulation of synapse formation and function, and regulation of the blood brain barrier permeability. Upon brain exposure to noxious stimuli, astrocytes can become reactive and activate neuroimmune responses. The nucleus accumbens (NAc) is a critical region involved in reward processing and is integrally involved in the establishment and maintenance of alcohol (ethanol, EtOH) dependence. Here we used the chronic intermittent ethanol – two-bottle choice (CIE-2BC) drinking model to induce EtOH dependence in Aldh1l1-eGFP/Rpl10a mice, which allow the pull-down of astrocyte specific RNA using translating ribosome affinity purification (TRAP) procedure. NAc astrocyte translating RNA and bulk-tissue RNA was analyzed by RNA-Seq to identify genes altered by EtOH dependence or EtOH drinking in astrocytes and the bulk NAc. The number of differentially regulated genes was greater in the astrocyte-specific analysis compared to the bulk-tissue suggesting the cell-type specific approach enables greater resolution of the effects of EtOH. In the astrocyte-specific translatome of EtOH dependent animals, genes related to neuroimmune activation were highly enriched with overall activation of pathways related to interferon and interleukin signaling. In addition, pathways relating to oxidative stress and glutathione related responses were enriched in NAc astrocytes from dependent animals. In contrast, the astrocyte response to EtOH drinking identified pathways related to homeostatic changes. These findings highlight the profound immune activation in NAc astrocytes during EtOH dependence which are distinct from the response to lower levels of EtOH exposure. This study identifies astrocyte pathways and genes involved in the transition from alcohol drinking to alcohol dependence and identify potential novel cell type-specific targets that underlie vulnerability to alcohol use.
Overall design Male and female mice CIE-2BC treated (dependent), 2BC controls (non-dependent), and ethanol naïve nucleus accumbens. Each brain sample from an individual mouse was fractionated into astrocyte translating RNA (IP) and bulk-tissue RNA (input).
Citation(s) 41192645
Submission date Sep 23, 2025
Last update date Nov 06, 2025
Contact name Marina Guizzetti
E-mail(s) guizzett@ohsu.edu
Phone 503-220-8262
Organization name Oregon Health & Science University; Portland VA Research Service
Department Behavioral Neuroscience
Lab Guizzetti Lab
Street address 3710 SW US Veterans Hospital Rd
City Portland
State/province OR
ZIP/Postal code 97239
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (95)
GSM9254882 NAc, C17, Female, Dependent, Input
GSM9254883 NAc, C17, Female, Dependent, IP
GSM9254884 NAc, G22, Female, Dependent, Input
GSM9254885 NAc, G22, Female, Dependent, IP
GSM9254886 NAc, I01, Female, non-Dependent, Input
GSM9254887 NAc, I01, Female, non-Dependent, IP
GSM9254888 NAc, I02, Female, Dependent, Input
GSM9254889 NAc, I02, Female, Dependent, IP
GSM9254890 NAc, I03, Male, non-Dependent, Input
GSM9254891 NAc, I03, Male, non-Dependent, IP
GSM9254892 NAc, I04, Female, non-Dependent, Input
GSM9254893 NAc, I04, Female, non-Dependent, IP
GSM9254894 NAc, I05, Female, Dependent, Input
GSM9254895 NAc, I05, Female, Dependent, IP
GSM9254896 NAc, I06, Male, non-Dependent, Input
GSM9254897 NAc, I06, Male, non-Dependent, IP
GSM9254898 NAc, I07, Male, Dependent, Input
GSM9254899 NAc, I07, Male, Dependent, IP
GSM9254900 NAc, I08, Female, non-Dependent, Input
GSM9254901 NAc, I08, Female, non-Dependent, IP
GSM9254902 NAc, I09, Female, Dependent, Input
GSM9254903 NAc, I09, Female, Dependent, IP
GSM9254904 NAc, I10, Male, non-Dependent, Input
GSM9254905 NAc, I11, Male, Dependent, Input
GSM9254906 NAc, I11, Male, Dependent, IP
GSM9254907 NAc, I12, Female, non-Dependent, Input
GSM9254908 NAc, I12, Female, non-Dependent, IP
GSM9254909 NAc, I13, Female, Dependent, Input
GSM9254910 NAc, I13, Female, Dependent, IP
GSM9254911 NAc, I14, Male, non-Dependent, Input
GSM9254912 NAc, I15, Male, Dependent, Input
GSM9254913 NAc, I15, Male, Dependent, IP
GSM9254914 NAc, I16, Female, non-Dependent, Input
GSM9254915 NAc, I16, Female, non-Dependent, IP
GSM9254916 NAc, J01, Female, Naïve, Input
GSM9254917 NAc, J01, Female, Naïve, IP
GSM9254918 NAc, J02, Male, Naïve, Input
GSM9254919 NAc, J02, Male, Naïve, IP
GSM9254920 NAc, J03, Male, non-Dependent, Input
GSM9254921 NAc, J03, Male, non-Dependent, IP
GSM9254922 NAc, J04, Female, non-Dependent, Input
GSM9254923 NAc, J04, Female, non-Dependent, IP
GSM9254924 NAc, J05, Male, Dependent, Input
GSM9254925 NAc, J05, Male, Dependent, IP
GSM9254926 NAc, J06, Female, Dependent, Input
GSM9254927 NAc, J06, Female, Dependent, IP
GSM9254928 NAc, J07, Male, Naïve, Input
GSM9254929 NAc, J07, Male, Naïve, IP
GSM9254930 NAc, J08, Female, Naïve, Input
GSM9254931 NAc, J08, Female, Naïve, IP
GSM9254932 NAc, J09, Female, Dependent, Input
GSM9254933 NAc, J09, Female, Dependent, IP
GSM9254934 NAc, J10, Male, Dependent, Input
GSM9254935 NAc, J10, Male, Dependent, IP
GSM9254936 NAc, J11, Male, non-Dependent, Input
GSM9254937 NAc, J11, Male, non-Dependent, IP
GSM9254938 NAc, K12, Female, non-Dependent, Input
GSM9254939 NAc, K12, Female, non-Dependent, IP
GSM9254940 NAc, K13, Female, Naïve, Input
GSM9254941 NAc, K13, Female, Naïve, IP
GSM9254942 NAc, K14, Male, Naïve, Input
GSM9254943 NAc, K14, Male, Naïve, IP
GSM9254944 NAc, K15, Male, non-Dependent, Input
GSM9254945 NAc, K15, Male, non-Dependent, IP
GSM9254946 NAc, K16, Female, non-Dependent, Input
GSM9254947 NAc, K16, Female, non-Dependent, IP
GSM9254948 NAc, K18, Male, Dependent, Input
GSM9254949 NAc, K18, Male, Dependent, IP
GSM9254950 NAc, K19, Male, Naïve, Input
GSM9254951 NAc, K19, Male, Naïve, IP
GSM9254952 NAc, K20, Female, Naïve, Input
GSM9254953 NAc, K20, Female, Naïve, IP
GSM9254954 NAc, K21, Male, Dependent, Input
GSM9254955 NAc, K21, Male, Dependent, IP
GSM9254956 NAc, L23, Male, Naïve, Input
GSM9254957 NAc, L24, Female, Naïve, Input
GSM9254958 NAc, L24, Female, Naïve, IP
GSM9254959 NAc, L25, Female, Dependent, Input
GSM9254960 NAc, L25, Female, Dependent, IP
GSM9254961 NAc, L26, Male, Dependent, Input
GSM9254962 NAc, L26, Male, Dependent, IP
GSM9254963 NAc, L27, Female, Naïve, Input
GSM9254964 NAc, L27, Female, Naïve, IP
GSM9254965 NAc, L28, Male, Naïve, Input
GSM9254966 NAc, L28, Male, Naïve, IP
GSM9254967 NAc, L29, Female, Dependent, Input
GSM9254968 NAc, L29, Female, Dependent, IP
GSM9254969 NAc, L30, Female, Naïve, Input
GSM9254970 NAc, L30, Female, Naïve, IP
GSM9254971 NAc, L31, Male, Naïve, Input
GSM9254972 NAc, L31, Male, Naïve, IP
GSM9254973 NAc, L32, Male, Naïve, Input
GSM9254974 NAc, L32, Male, Naïve, IP
GSM9254975 NAc, L33, Female, Naïve, Input
GSM9254976 NAc, L33, Female, Naïve, IP
Relations
BioProject PRJNA1333313

Download family Format

Supplementary file Size Download File type/resource
GSE308880_INIA_NAc_RAW_Counts.csv.gz 3.4 Mb (ftp) (http) CSV
Raw data are available in SRA

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