{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:00Z","timestamp":1787013780551,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T00:00:00Z","timestamp":1446681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NIAAA","award":["U01AA019925"],"award-info":[{"award-number":["U01AA019925"]}]},{"name":"NIH\/NIAAA INIA","award":["UO1AA020938"],"award-info":[{"award-number":["UO1AA020938"]}]},{"name":"NIH\/NIDA","award":["DA031833"],"award-info":[{"award-number":["DA031833"]}]},{"name":"NIH\/NIDA","award":["2T32NS51156-6"],"award-info":[{"award-number":["2T32NS51156-6"]}]},{"DOI":"10.13039\/100009429","name":"NRSA","doi-asserted-by":"crossref","award":["1F32NS083283-01A1"],"award-info":[{"award-number":["1F32NS083283-01A1"]}],"id":[{"id":"10.13039\/100009429","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Veteran Affairs Senior Research Career Scientist award"},{"name":"VA Merit Review","award":["BX-002128-01"],"award-info":[{"award-number":["BX-002128-01"]}]},{"name":"VA Merit Review","award":["BX002888"],"award-info":[{"award-number":["BX002888"]}]},{"name":"VA Career Development Award","award":["2-010-10S"],"award-info":[{"award-number":["2-010-10S"]}]},{"name":"Institute for Medical Research"},{"name":"DVAMC VSN 6 MIRECC"},{"name":"Career Development Award","award":["1lK2BX002505"],"award-info":[{"award-number":["1lK2BX002505"]}]},{"name":"Esther and Joseph Klingenstein Fund Fellow"},{"name":"Alfred P. Sloan Fellow"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adolescent intermittent alcohol exposure (AIE) has profound effects on neuronal function. We have previously shown that AIE causes aberrant hippocampal structure and function that persists into adulthood. However, the possible contributions of astrocytes and their signaling factors remain largely unexplored. We investigated the acute and enduring effects of AIE on astrocytic reactivity and signaling on synaptic expression in the hippocampus, including the impact of the thrombospondin (TSP) family of astrocyte\u2010secreted synaptogenic factors and their neuronal receptor, alpha2delta\u20101 (\u03b12\u03b4\u20101). Our hypothesis is that some of the influences of AIE on neuronal function may be secondary to direct effects on astrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted Western blot analysis on TSPs 1 to 4 and \u03b12\u03b4\u20101 from whole hippocampal lysates 24\u00a0hours after the 4th and 10th doses of AIE, then 24\u00a0days after the last dose (in adulthood). We used immunohistochemistry to assess astrocyte reactivity (i.e., morphology) and synaptogenesis (i.e., colocalization of pre\u2010 and postsynaptic puncta).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Adolescent AIE reduced \u03b12\u03b4\u20101 expression, and colocalized pre\u2010 and postsynaptic puncta after the fourth ethanol (EtOH) dose. By the 10th dose, increased TSP2 levels were accompanied by an increase in colocalized pre\u2010 and postsynaptic puncta, while \u03b12\u03b4\u20101 returned to control levels. Twenty\u2010four days after the last EtOH dose (i.e., adulthood), TSP2, TSP4, and \u03b12\u03b4\u20101 expression were all elevated. Astrocyte reactivity, indicated by increased astrocytic volume and area, was also observed at that time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Repeated EtOH exposure during adolescence results in long\u2010term changes in specific astrocyte signaling proteins and their neuronal synaptogenic receptor. Continued signaling by these traditionally developmental factors in adulthood may represent a compensatory mechanism whereby astrocytes reopen the synaptogenic window and repair lost connectivity, and consequently contribute to the enduring maladaptive structural and functional abnormalities previously observed in the hippocampus after AIE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.12913","type":"journal-article","created":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T07:07:01Z","timestamp":1446707221000},"page":"2403-2413","source":"Crossref","is-referenced-by-count":69,"title":["Adolescent Intermittent Alcohol Exposure: Dysregulation of Thrombospondins and Synapse Formation are Associated with Decreased Neuronal Density in the Adult Hippocampus"],"prefix":"10.1111","volume":"39","author":[{"given":"Mary\u2010Louise","family":"Risher","sequence":"first","affiliation":[{"name":"Durham VA Medical Center Duke University Medical Center Durham North Carolina"},{"name":"Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah G.","family":"Sexton","sequence":"additional","affiliation":[{"name":"Durham VA Medical Center Duke University Medical Center Durham North Carolina"},{"name":"Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Christopher","family":"Risher","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilkie A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Social Sciences Research Institute Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah L.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Durham VA Medical Center Duke University Medical Center Durham North Carolina"},{"name":"Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger D.","family":"Madison","sequence":"additional","affiliation":[{"name":"Durham VA Medical Center Duke University Medical Center Durham North Carolina"},{"name":"Department of Neurosurgery Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Moore","sequence":"additional","affiliation":[{"name":"Durham VA Medical Center Duke University Medical Center Durham North Carolina"},{"name":"Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cagla","family":"Eroglu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Scott","family":"Swartzwelder","sequence":"additional","affiliation":[{"name":"Durham VA Medical Center Duke University Medical Center Durham North Carolina"},{"name":"Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina"},{"name":"Department of Psychology and Neuroscience Duke University Medical Center Durham North 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