title: Interactions between chronic ethanol consumption and thiamine deficiency on neural plasticity, spatial memory, and cognitive flexibility.
abstract: BACKGROUND
  Many alcoholics display moderate to severe cognitive dysfunction accompanied by brain pathology. A factor confounded with prolonged heavy alcohol consumption is poor nutrition, and many alcoholics are thiamine deficient. Thus, thiamine deficiency (TD) has emerged as a key factor underlying alcohol-related brain damage (ARBD). TD in humans can lead to Wernicke Encephalitis that can progress into Wernicke-Korsakoff syndrome and these disorders have a high prevalence among alcoholics. Animal models are critical for determining the exact contributions of ethanol (EtOH)- and TD-induced neurotoxicity, as well as the interactions of those factors to brain and cognitive dysfunction.
  
  
  METHODS
  Adult rats were randomly assigned to 1 of 6 treatment conditions: chronic EtOH treatment (CET) where rats consumed a 20% v/v solution of EtOH over 6 months; severe pyrithiamine-induced TD (PTD-moderate acute stage); moderate PTD (PTD-early acute stage); moderate PTD followed by CET (PTD-CET); moderate PTD during CET (CET-PTD); and pair-fed (PF) control. After recovery from treatment, all rats were tested on spontaneous alternation and attentional set-shifting. After behavioral testing, brains were harvested for determination of mature brain-derived neurotrophic factor (BDNF) and thalamic pathology.
  
  
  RESULTS
  Moderate TD combined with CET, regardless of treatment order, produced significant impairments in spatial memory, cognitive flexibility, and reductions in brain plasticity as measured by BDNF levels in the frontal cortex and hippocampus. These alterations are greater than those seen in moderate TD alone, and the synergistic effects of moderate TD with CET lead to a unique cognitive profile. However, CET did not exacerbate thalamic pathology seen after moderate TD.
  
  
  CONCLUSIONS
  These data support the emerging theory that subclinical TD during chronic heavy alcohol consumption is critical for the development of significant cognitive impairment associated with ARBD.
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, Binghamton, New York.
authors.forename: Lindsey C
authors.initials: LC
authors.lastname: Vedder
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, Binghamton, New York.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Hall
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, Binghamton, New York.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Jabrouin
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, Binghamton, New York.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Savage
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000097:blood; D000818:Animals; D003072:Cognition Disorders / Q000097:blood* / Q000139:chemically induced / Q000523:psychology; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology; D013832:Thiamine Deficiency / Q000097:blood* / Q000150:complications / Q000523:psychology
chemical_list: D000431:Ethanol
keywords: Alcohol-Related Brain Damage; Alcoholism; Attentional Set-Shifting; Brain-Derived Neurotropic Factor; Hippocampus; Prefrontal Cortex; Spontaneous Alternation; Thalamus; Thiamine Deficiency; Wernicke-Korsakoff Syndrome