title: Prenatal lipopolysaccharide does not accelerate progressive dopamine neuron loss in the rat as a result of normal aging.
abstract: We previously demonstrated that in utero exposure to the bacteriotoxin lipopolysaccharide (LPS) led to the birth of rat pups with fewer than normal dopamine (DA) neurons. These animals exhibited significant neuroinflammation in the nigrostriatal pathway creating the possibility that they could exhibit further, progressive DA neuron loss over their lives. To study this possibility, we injected gravid female rats i.p. at 10,000 endotoxin units (EUs) of LPS per kg or saline at embryonic (E) day 10.5 and assigned pups to sacrifice groups at 4, 14 and 17 months such that littermates were sacrificed at each end point. The effects of prenatal LPS on DA cell counts and striatal DA were significantly reduced relative to controls whereas DA activity and numbers of activated microglia (OX-6ir cell) were statistically increased. However, the progressive DA neuron loss was parallel to that of the controls suggesting that prenatal LPS does not produce an accelerated rate of DA neuron loss. Interestingly, locomotor activity was increased after 3 months in animals exposed to LPS prenatally, but by 16 months, was significantly reduced relative to controls. Additionally, animals exposed to LPS prenatally exhibited Lewy body-like inclusions that were first seen in 14 month old animals. These data broadly support previous studies demonstrating that prenatal exposure to LPS, as frequently occurs in humans as part of Bacterial Vaginosis, leads to the birth of animals with fewer than normal DA neurons. The progressive DA neuron loss seen in these animals is, however, primarily a result of normal aging.
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Cohn Research Building, Suite 406, 1735 W. Harrison St., Chicago, IL 60612, USA. lingzdl@yahoo.com
authors.forename: Zaodung
authors.initials: Z
authors.lastname: Ling
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chong Wai
authors.initials: CW
authors.lastname: Tong
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Snyder
authors.forename: Jack W
authors.initials: JW
authors.lastname: Lipton
authors.forename: Paul M
authors.initials: PM
authors.lastname: Carvey
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002452:Cell Count / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D016631:Lewy Bodies / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid