title: Transgenerational transmission of an anticholinergic endophenotype with memory dysfunction.
abstract: Impaired cholinergic neurotransmission associated with cognitive dysfunction occurs in various mental disorders of different etiologies including Alzheimer's disease and postalcoholic dementia and others. To address the question whether there exists a common endophenotype with a defined genetic and/or epigenetic signature causing mental dysfunction in these disorders, we investigated 2 generations of offspring born to alcohol-treated mothers. Here, we show that memory impairment and reduced synthesis of acetylcholine occurs in both F1 (exposed to ethanol in utero) and F2 generation (never been exposed to ethanol). Effects in the F2 generation are most likely consequences of transgenerationally transmitted epigenetic modifications in stem cells induced by alcohol. This clearly documents the role of ancestral history of drug abuse on the brain development of subsequent generations. The results further suggest an epigenetic trait for an anticholinergic endophenotype associated with cognitive dysfunction which might be relevant to our understanding of mental impairment in neurodegenerative disorders such as Alzheimer's disease and related disorders.
authors.affiliation: Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.affiliation: Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany.
authors.forename: Lieselotte
authors.initials: L
authors.lastname: Praße
authors.affiliation: Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Wolpers
authors.affiliation: Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany.
authors.forename: Martina K
authors.initials: MK
authors.lastname: Brückner
authors.affiliation: Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Ueberham
authors.affiliation: Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany. Electronic address: aret@medizin.uni-leipzig.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis*; D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics*; D058068:Endophenotypes; D044127:Epigenesis, Genetic; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics; D008431:Maternal-Fetal Exchange; D008569:Memory Disorders / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics*; D051381:Rats
chemical_list: D000431:Ethanol; D000109:Acetylcholine
keywords: Cholinergic system; Cognitive function; Epigenetic trait; Ethanol; Fetal alcohol spectrum disorders; Neurotoxic damage