Adolescent intermittent alcohol exposure: persistence of structural and functional hippocampal abnormalities into adulthood.
BACKGROUND
Human adolescence is a crucial stage of neurological development during which ethanol (EtOH) consumption is often at its highest. Alcohol abuse during adolescence may render individuals at heightened risk for subsequent alcohol abuse disorders, cognitive dysfunction, or other neurological impairments by irreversibly altering long-term brain function. To test this possibility, we modeled adolescent alcohol abuse (i.e., intermittent EtOH exposure during adolescence [AIE]) in rats to determine whether adolescent exposure to alcohol leads to long-term structural and functional changes that are manifested in adult neuronal circuitry.


METHODS
We specifically focused on hippocampal area CA1, a brain region associated with learning and memory. Using electrophysiological, immunohistochemical, and neuroanatomical approaches, we measured post-AIE changes in synaptic plasticity, dendritic spine morphology, and synaptic structure in adulthood.


RESULTS
We found that AIE-pretreated adult rats manifest robust long-term potentiation, induced at stimulus intensities lower than those required in controls, suggesting a state of enhanced synaptic plasticity. Moreover, AIE resulted in an increased number of dendritic spines with characteristics typical of immaturity. Immunohistochemistry-based analysis of synaptic structures indicated a significant decrease in the number of co-localized pre- and postsynaptic puncta. This decrease is driven by an overall decrease in 2 postsynaptic density proteins, PSD-95 and SAP102.


CONCLUSIONS
Taken together, these findings reveal that repeated alcohol exposure during adolescence results in enduring structural and functional abnormalities in the hippocampus. These synaptic changes in the hippocampal circuits may help to explain learning-related behavioral changes in adult animals preexposed to AIE.
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Mary-Louise
ML
Risher
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Rebekah L
RL
Fleming
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina.
W Christopher
WC
Risher
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
K M
KM
Miller
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Rebecca C
RC
Klein
Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, Tennessee.
Tiffany
T
Wills
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Shawn K
SK
Acheson
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Scott D
SD
Moore
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Social Sciences Research Institute, Duke University Medical Center, Durham, North Carolina.
Wilkie A
WA
Wilson
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina.
Cagla
C
Eroglu
Durham VA Medical Center, Duke University Medical Center, Durham, North Carolina.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.|Department of Psychology and Neuroscience, Duke University Medical Center, Durham, North Carolina.
H S
HS
Swartzwelder
D000375:Aging / Q000187:drug effects* / Q000473:pathology* / Q000523:psychology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein; D000431:Ethanol / Q000009:adverse effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000076122:Disks Large Homolog 4 Protein; C101195:Dlg3 protein, rat; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D000431:Ethanol
Adolescence; Dendritic Spines; Ethanol; Hippocampus; Long-Term Potentiation