BACKGROUND: Adolescent intermittent @entity285 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-secreted synaptogenic factors and their neuronal receptor, alpha2delta-1 (a2  -1). Our hypothesis is that some of the influences of AIE on neuronal function may be secondary to direct effects on astrocytes. METHODS: We conducted Western blot analysis on TSPs 1 to 4 and a2  -1 from whole hippocampal lysates 24  hours after the 4th and 10th doses of AIE, then 24  days after the last dose (in adulthood). We used immunohistochemistry to assess astrocyte reactivity (i.e., morphology) and synaptogenesis (i.e., colocalization of pre- and postsynaptic puncta). RESULTS: Adolescent AIE reduced a2  -1 expression, and colocalized pre- and postsynaptic puncta after the fourth @entity1068 ( @entity167 ) dose. By the 10th dose, increased @entity18180 levels were accompanied by an increase in colocalized pre- and postsynaptic puncta, while a2  -1 returned to control levels. Twenty-four days after the last @entity167 dose (i.e., adulthood), @entity18180 , @entity37220 , and a2  -1 expression were all elevated. Astrocyte reactivity, indicated by increased astrocytic volume and area, was also observed at that time. CONCLUSIONS: Repeated @entity167 exposure during adolescence results in long-term 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 @entity2383 previously observed in the hippocampus after AIE.

Adolescent Intermittent XXXX Exposure: Dysregulation of Thrombospondins and Synapse Formation are Associated with Decreased Neuronal Density in the Adult Hippocampus.

@entity37220 :: ('7060', 'Gene') :: ['TSP4'] @entity167 :: ('CHEBI:16236', 'Chemical') :: ['EtOH'] @entity18180 :: ('7058', 'Gene') :: ['TSP2'] @entity285 :: ('D000431', 'Chemical') :: ['alcohol'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['ethanol'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['maladaptive structural and functional abnormalities']
@entity285 :: (D000431,Chemical) :: ['Alcohol']
