ArticleAlcoholism, clinical and experimental research2015
Adolescent Intermittent Alcohol Exposure: Dysregulation of Thrombospondins and Synapse Formation are Associated with Decreased Neuronal Density in the Adult Hippocampus.
Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- Adolescent alcohol exposure disrupts astrocyte-synaptic structural and functional coupling in the male dorsal hippocampus.Molecular psychiatry · 2026Article
- MAO-B status in alcohol use disorder: a [Molecular psychiatry · 2026Article
- Astrocytes and Alcohol Throughout the Lifespan.Biological psychiatry · 2026Review
- Article
- Mechanisms of Alcohol Interference with Hippocampal Neurogenesis and its Repair Strategies.Molecular neurobiology · 2025Review
- Astrocyte alterations and dysfunction in alcohol use disorder: A comprehensive scoping review of clinical postmortem and preclinical evidence.Progress in neuro-psychopharmacology & biological psychiatry · 2025Article
- Article
- Modeling Brain Gene Expression in Alcohol Use Disorder with Genetic Animal Models.Current topics in behavioral neurosciences · 2025Review
- Nicotine Motivated Behavior inInternational journal of molecular sciences · 2024Article
- Adolescent intermittent ethanol exposure alters adult exploratory and affective behaviors, and cerebellar Grin2b expression in C57BL/6J mice.Drug and alcohol dependence · 2023Article
- Astrocytes in human central nervous system diseases: a frontier for new therapies.Signal transduction and targeted therapy · 2023Review
- Astrocyte-specific CaBiochemistry and cell biology = Biochimie et biologie cellulaire · 2023Review
- Sex-dependent factors of alcohol and neuroimmune mechanisms.Neurobiology of stress · 2023Article
- Adolescent intermittent ethanol exposure enhances adult stress effects in male rats.Pharmacology, biochemistry, and behavior · 2023Article
- Adolescent intermittent ethanol exposure reduces astrocyte-synaptic proximity in the adult medial prefrontal cortex in rats: Reversal by gabapentin.Addiction neuroscience · 2022Article
- Article
- Sex differences in the effects of adolescent intermittent ethanol exposure on exploratory and anxiety-like behavior in adult rats.Alcohol (Fayetteville, N.Y.) · 2022Article
- Adolescent brain maturation and the neuropathological effects of binge drinking: A critical review.Frontiers in neuroscience · 2022Review
- Acute Ethanol Challenge Differentially Regulates Expression of Growth Factors and miRNA Expression Profile of Whole Tissue of the Dorsal Hippocampus.Frontiers in neuroscience · 2022Article
- Effects of adolescent intermittent ethanol on hippocampal expression of glutamate homeostasis and astrocyte-neuronal tethering proteins in male and female rats.Journal of neuroscience research · 2021Article
Corrections and comments
- Erratum issuedErratum.2016
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAdolescent 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-secreted synaptogenic factors and their neuronal receptor, alpha2delta-1 (α2δ-1). Our hypothesis is that some of the influences of AIE on neuronal function may be secondary to direct effects on astrocytes.
methodsWe conducted Western blot analysis on TSPs 1 to 4 and α2δ-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).
resultsAdolescent AIE reduced α2δ-1 expression, and colocalized pre- and postsynaptic puncta after the fourth ethanol (EtOH) dose. By the 10th dose, increased TSP2 levels were accompanied by an increase in colocalized pre- and postsynaptic puncta, while α2δ-1 returned to control levels. Twenty-four days after the last EtOH dose (i.e., adulthood), TSP2, TSP4, and α2δ-1 expression were all elevated. Astrocyte reactivity, indicated by increased astrocytic volume and area, was also observed at that time.
conclusionsRepeated EtOH 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 maladaptive structural and functional abnormalities previously observed in the hippocampus after AIE.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.