PMID- 15795061
OWN - NLM
STAT- MEDLINE
DCOM- 20050527
LR  - 20151119
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 209
IP  - 3
DP  - 2005 May 5
TI  - Maternal exposure of rats to nicotine via infusion during gestation produces 
      neurobehavioral deficits and elevated expression of glial fibrillary acidic 
      protein in the cerebellum and CA1 subfield in the offspring at puberty.
PG  - 245-61
AB  - Maternal smoking during pregnancy is known to be a significant contributor to 
      developmental neurological health problems in the offspring. In animal studies, 
      nicotine treatment via injection during gestation has been shown to produce 
      episodic hypoxia in the developing fetus. Nicotine delivery via mini osmotic 
      pump, while avoiding effects due to hypoxia-ischemia, it also provides a steady 
      level of nicotine in the plasma. In the present study timed-pregnant 
      Sprague-Dawley rats (300-350 g) were treated with nicotine (3.3 mg/kg, in 
      bacteriostatic water via s.c. implantation of mini osmotic pump) from gestational 
      days (GD) 4-20. Control animals were treated with bacteriostatic water via s.c. 
      implantation of mini osmotic pump. Offspring on postnatal day (PND) 30 and 60, 
      were evaluated for changes in the ligand binding for various types of nicotinic 
      acetylcholine receptors and neuropathological alterations. Neurobehavioral 
      evaluations for sensorimotor functions, beam-walk score, beam-walk time, incline 
      plane and grip time response were carried out on PND 60 offspring. Beam-walk time 
      and forepaw grip time showed significant impairments in both male and female 
      offspring. Ligand binding densities for [3H]epibatidine, [3H]cytisine and 
      [3H]alpha-bungarotoxin did not show any significant changes in nicotinic 
      acetylcholine receptors subtypes in the cortex at PND 30 and 60. 
      Histopathological evaluation using cresyl violet staining showed significant 
      decrease in surviving Purkinje neurons in the cerebellum and a decrease in 
      surviving neurons in the CA1 subfield of hippocampus on PND 30 and 60. An 
      increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed 
      in cerebellum white matter as well as granular cell layer of cerebellum and the 
      CA1 subfield of hippocampus on PND 30 and 60 of both male and female offspring. 
      These results indicate that maternal exposure to nicotine produces significant 
      neurobehavioral deficits, a decrease in the surviving neurons and an increased 
      expression of GFAP in cerebellum and CA1 subfield of hippocampus of the offspring 
      on PND 30 and 60. The results show that although 60-day-old male and female rat 
      offspring of mothers exposed to nicotine during gestation did not differ from 
      control in body weight gain or nicotinic acetylcholine receptors ligand binding, 
      they exhibited significant sensorimotor deficits that were consistent with the 
      neuropathological alterations seen in the brain. These neurobehavioral and 
      pathological deficits indicate that maternal nicotine exposure may produce 
      long-term adverse health effects in the offspring.
FAU - Abdel-Rahman, Ali
AU  - Abdel-Rahman A
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, NC 27710, USA.
FAU - Dechkovskaia, Anjelika M
AU  - Dechkovskaia AM
FAU - Sutton, Jazmine M
AU  - Sutton JM
FAU - Chen, Wei-Chung
AU  - Chen WC
FAU - Guan, Xiangrong
AU  - Guan X
FAU - Khan, Wasiuddin A
AU  - Khan WA
FAU - Abou-Donia, Mohamed B
AU  - Abou-Donia MB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Receptors, Nicotinic)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Cerebellum/*drug effects/metabolism/pathology
MH  - Female
MH  - Glial Fibrillary Acidic Protein/biosynthesis
MH  - Hippocampus/*drug effects/metabolism/pathology
MH  - Infusion Pumps, Implantable
MH  - Male
MH  - Maternal Exposure
MH  - Nicotine/antagonists & inhibitors/*toxicity
MH  - Nicotinic Agonists/metabolism
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Psychomotor Disorders/*chemically induced
MH  - Psychomotor Performance
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Nicotinic/metabolism
MH  - Sexual Maturation
EDAT- 2005/03/30 09:00
MHDA- 2005/05/28 09:00
CRDT- 2005/03/30 09:00
PHST- 2004/07/01 00:00 [received]
PHST- 2004/12/21 00:00 [revised]
PHST- 2004/12/30 00:00 [accepted]
PHST- 2005/03/30 09:00 [pubmed]
PHST- 2005/05/28 09:00 [medline]
PHST- 2005/03/30 09:00 [entrez]
AID - S0300-483X(05)00015-6 [pii]
AID - 10.1016/j.tox.2004.12.037 [doi]
PST - ppublish
SO  - Toxicology. 2005 May 5;209(3):245-61. doi: 10.1016/j.tox.2004.12.037.