Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.
Repeated maternal separation of rat pups during the early postnatal period may affect brain-derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced-swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age-dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats.
Greisen
Mia H
MH
Laboratory of Neuropsychiatry, Copenhagen University Hospital, Copenhagen, Denmark. mia@soendergaard.org
Altar
C Anthony
CA
Bolwig
Tom G
TG
Whitehead
Richard
R
Wörtwein
Gitta
G
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008426:Maternal Deprivation; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D013550:Swimming
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D001973:Bromodeoxyuridine