title: Neonatal alcohol exposure reduces number of parvalbumin-positive interneurons in the medial prefrontal cortex and impairs passive avoidance acquisition in mice deficits not rescued from exercise.
abstract: Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored. Male C57BL/6J mice received either saline or 5g/kg ethanol (two doses, two hours apart) on PD 5, 7, and 9. On PD 35, animals received a running wheel or remained sedentary for 48days before behavioral testing and perfusion on PD 83. The number of PV+ interneurons was stereologically measured in three separate mPFC subregions: infralimbic, prelimbic and anterior cingulate cortices (ACC). Neonatal alcohol exposure decreased number of PV+ interneurons and volume of the ACC, but the other regions of the mPFC were spared. Alcohol impaired acquisition, but not retrieval of passive avoidance, and had no effect on motor performance on the rotarod. Exercise had no impact on PV+ cell number, mPFC volume, or acquisition of passive avoidance, but enhanced retrieval in both control and alcohol-exposed groups, and enhanced rotarod performance in the control mice. Results support the hypothesis that part of the behavioral deficits associated with developmental alcohol exposure are due to reduced PV+ interneurons in the ACC, but unfortunately exercise does not appear to be able to reverse any of these deficits.
authors.affiliation: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: gillianh@illinois.edu.
authors.forename: G F
authors.initials: GF
authors.lastname: Hamilton
authors.affiliation: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: I J
authors.initials: IJ
authors.lastname: Hernandez
authors.affiliation: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Krebs
authors.affiliation: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Bucko
authors.affiliation: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Rhodes
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000473:pathology / Q000534:rehabilitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010320:Parvalbumins / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000473:pathology; D011596:Psychomotor Disorders / Q000209:etiology
chemical_list: D002492:Central Nervous System Depressants; C577485:Nes protein, mouse; D064231:Nestin; D010320:Parvalbumins; D000431:Ethanol
keywords: anterior cingulate cortex; executive function; fear; fetal alcohol spectrum disorders; inhibition; running