title: Presynaptic glutamatergic function in dentate gyrus in vivo is diminished by chronic exposure to inorganic lead.
abstract: Reductions in membrane Ca2+ channel currents and depolarization-evoked neurotransmitter release have been repeatedly observed as a result of acute exposure to Pb2+. This study was performed to determine whether hippocampal glutamate and GABA release are impaired in intact animals chronically exposed to lead (Pb). As paired-pulse facilitation in the hippocampus is primarily mediated by an enhancement of glutamate release, this neurophysiological measure was also assessed in the dentate gyrus of Pb-exposed animals. Pregnant dams received 0.2% Pb acetate in the drinking water at parturition, and male offspring were weaned to the same solution as that given their dams. Control animals were maintained on distilled water. As adults, animals had intracerebral dialysis probes inserted through guide cannulae implanted 2-4 days previously and the hippocampal CAI-dentate area was perfused with modified Ringer's solution. Transmitter release was induced by perfusion with 150 mM K+ with half the animals in each group tested with Ca2+ present in the perfusate (total release) and the other half with Ca2+ absent (Ca(2+)-independent release). K(+)-stimulated total glutamate release was reduced in Pb-exposed animals relative to controls. No group differences were observed under Ca(2+)-free conditions, indicating that Ca(2+)-dependent glutamate release was decreased in exposed rats. In contrast no group differences in K(+)-stimulated total GABA release were evident, whereas an augmentation in GABA release under Ca(2+)-free conditions was revealed in Pb-exposed animals. The effects of exposure on the Ca(2+)-dependent components of release are consistent with in vitro evidence indicating an inhibitory action of Pb2+ at voltage-sensitive Ca2+ channels. A separate group of animals was prepared under urethane anesthesia with stimulating and recording electrodes placed in the perforant path and dentate gyrus, respectively. Pairs of stimulus pulses were delivered at interpulse intervals (IPI) of 10-250 ms. Pb exposure induced an increase in paired-pulse depression at the 20 ms 1PI and reduced paired-pulse facilitation at the 30 ms IPI. Decreases in paired-pulse facilitation could not be attributed to the reported effects of Pb2+ on N-methyl-D-aspartate (NMDA) receptors as MK-801 (1.0 mg/kg, s.c.) administration produced an opposing pattern of effects on paired-pulse measures. The Pb-induced suppression of paired-pulse facilitation is consistent with exposure-related decreases in total glutamate release. The impact of these effects of Pb exposure on hippocampal glutamatergic transmission may contribute to the reported effects of Pb on other forms of synaptic plasticity including long-term potentiation, a model of learning and memory.
authors.affiliation: Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria 61656, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Lasley
authors.forename: M E
authors.initials: ME
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D002118:Calcium / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000503:physiopathology*; D008297:Male; D017551:Microdialysis; D009942:Organometallic Compounds / Q000633:toxicity*; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D011188:Potassium; C008261:lead acetate; D002118:Calcium