The effect of mercury vapour on cholinergic neurons in the fetal brain: studies on the expression of nerve growth factor and its low- and high-affinity receptors.
The effects of mercury vapour on the production of nerve growth factor during development have been examined. Pregnant rats were exposed to two different concentrations of mercury vapour during either embryonic days E6-E11 (early) or E13-E18 (late) in pregnancy, increasing the postnatal concentration of mercury in the brain from 1 ng/g tissue to 4 ng/g tissue (low-dose group) or 11 ng/g (high-dose group). The effect of this exposure in offspring was determined by looking at the NGF concentration at postnatal days 21 and 60 and comparing these levels to age-matched controls from sham-treated mothers. Changes in the expression of mRNA encoding NGF, the low- and high-affinity receptors for NGF (p75 and p140 trk, respectively) and choline acetyltransferase (ChAT) were also determined. When rats were exposed to high levels of mercury vapour during early embryonic development there was a significant (62%) increase in hippocampal NGF levels at P21 accompanied by a 50% decrease of NGF in the basal forebrain. The expression of NGF mRNA was found to be unaltered in the dentate gyrus. The expression of p75 mRNA was significantly decreased to 39% of control levels in the diagonal band of Broca (DB) and to approximately 50% in the medial septal nucleus (MS) whereas no alterations in the level of trk mRNA expression were detectable in the basal forebrain. ChAT mRNA was slightly decreased in the DB and MS, significantly in the striatum. These findings suggest that low levels of prenatal mercury vapour exposure can alter the levels of the NGF and its receptors, indicating neuronal damage and disturbed trophic regulations during development.
Söderström
S
S
Department of Developmental Neuroscience, Uppsala University, Sweden.
Fredriksson
A
A
Dencker
L
L
Ebendal
T
T
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology*; D048429:Cell Size; D002795:Choline O-Acetyltransferase / Q000235:genetics; D002799:Cholinergic Fibers / Q000737:chemistry / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry; D017403:In Situ Hybridization; D008628:Mercury / Q000009:adverse effects*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D008628:Mercury