The stamp of ancestry: roots of behavioral and neuronal impairment in adulthood.
Exposure of pregnant animals to noxious conditions affects neuronal function in the offspring. However, exposure or treatment of the maternal animal during pregnancy affects both ancestor and offspring. In the present study, female CD-1 mice were repetitively treated with 3-nitropropionate (3-np), a selective inhibitor of succinic dehydrogenase, exclusively prior to mating. Clinically, mice appeared normal during treatment. Five days after cessation of treatment animals were mated with control male animals. At 4 months of age spatial learning, LTP, NADH autofluorescence, and hypoxic tolerance were alike in controls and the offspring of treated female ancestors. However, an additional metabolic challenge in the offspring unmasks impairment of spatial learning, diminution of long-term potentiation (LTP), an altered protein microenvironment of mitochondrial enzymes, and reduced hypoxic tolerance. We conclude that the exposure of maternal ancestors to subclinical repetitive impairment of oxidative phosphorylation fosters impairment of behavior and neuronal function in the adult offspring, becoming apparent only on additional challenge. This finding may ultimately help to understand the causes of neuronal impairment or even neuropsychiatric disease in old age.
Lohmann
Peter
P
Department of Psychiatry, Mental Health and Old Age Psychiatry, Charité Medical University, Eschenallee 3, D-14050 Berlin, Germany.
Lange-Asschenfeldt
Christian
C
Huber
Roman
R
Riepe
Matthias W
MW
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009243:NAD / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009574:Nitro Compounds / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011422:Propionates / Q000009:adverse effects; D013050:Spectrometry, Fluorescence
D009574:Nitro Compounds; D011422:Propionates; D009243:NAD; C015392:3-nitropropionic acid