Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life.
Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain.



Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59.



Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group.



These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life.
Department of Neurobiology and Anatomy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV.
Lan
L
Xiao
Department of Neurobiology and Anatomy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV.
Vincent L
VL
Kish
Department of Neurobiology and Anatomy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV.
Katherine M
KM
Benders
Department of Neurobiology and Anatomy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV zwu@hsc.wvu.edu.
Zhong-Xin
ZX
Wu
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D015536:Down-Regulation; D005260:Female; D005865:Gestational Age; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D019570:Inhalation Exposure / Q000009:adverse effects*; D008124:Locomotion; D018811:Maternal Exposure / Q000009:adverse effects*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008813:Mice, Inbred ICR; D009043:Motor Activity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D020813:Receptor, trkB
D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D014028:Tobacco Smoke Pollution; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB
Brain-derived neurotrophic factor; pregnancy smoking.; tropomyosin receptor kinase B