Abstract
The aim of the present study was to investigate whether functional changes at CA3-CA1 synapses in the hippocampus could underlie learning and memory deficits produced in rat offspring by a prenatal exposure model simulating the carbon monoxide (CO) exposure observed in human cigarette smokers. Electrophysiological endpoints, including long-term potentiation, were examined in 15- to 30-day-old male rats whose mothers were exposed, from day 0 to day 20 of gestation, to 150 ppm of CO resulting in blood levels of carboxyhemoglobin comparable to those found in human cigarette smokers. Evoked field excitatory postsynaptic potentials were measured in the stratum radiatum in hippocampal slices. Results show that before tetanus, input/output functions, presynaptic volley, and paired-pulse facilitation were not affected in CO-exposed offspring, indicating that basal synaptic excitability and terminal Ca2+ influx were not influenced by prenatal exposure to this gas. Conversely, evoked field excitatory postsynaptic potentials potentiation in response to tetanization was reduced by about 23% and decayed rapidly to baseline values in slices from CO-exposed animals. No changes between and within groups were observed in paired-pulse facilitation after tetanus. The selective impairment of long-term potentiation expression exhibited by CO-exposed rats was paralleled by a significant decrease in heme-oxygenase 2 and neuronal nitric-oxide synthase in the hippocampus. No changes in either enzymatic activity were found in frontal cortex and cerebellum. These electrophysiological and biochemical alterations might account for cognitive deficits previously observed in rats exposed prenatally to CO. Our findings could have clinical implications for the offspring of mothers who smoke during pregnancy.
Footnotes
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Send reprint requests to: Vincenzo Cuomo, M.D, Ph.D., Department of Pharmacology and Human Physiology, Medical School-University of Bari, Policlinico-Piazza Giulio Cesare 11, 70124 Bari, Italy. E-mail: cuomo{at}cimedoc.uniba.it
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↵1 Supported by Ministero dell'Università e della Ricerca Scientifica e Tecnologica (Cofinanziamenti 1997–1999), Regione Autonoma della Sardegna, Fondazione Banco di Sardegna, Consiglio Nazionale delle Richerche (97.04632. CT13; 98.00730. PS13) grants.
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↵2 Current address: Department of Experimental Biology, University of Cagliari, Cittadella Universitaria Monserrato, 09042 Monserrato-Cagliari, Italy.
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↵3 Current address: Department of Physiology and Biochemistry, University of Pisa, Via S. Zeno 31, 056127 Pisa, Italy.
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↵4 Current address: “Bernard Brodie” Dept. of Neuroscience, University of Cagliari, Via Porcell 4, 09124 Cagliari, Italy.
- Abbreviations:
- CO
- carbon monoxide
- NO
- nitric oxide
- LTP
- long-term potentiation
- I/O
- input/output
- PTP
- post-tetanic potentiation
- STP
- short-term potentiation
- PPF
- paired-pulse facilitation
- AMPA
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
- HO
- heme-oxygenase
- NOS
- NO synthase
- nNOS
- neuronal NOS
- GD
- gestational day
- HbCO
- carboxyhemoglobin
- f-EPSPs
- field excitatory postsynaptic potentials
- NMDA
- N-methyl-d-aspartate
- Received January 7, 2000.
- Accepted April 11, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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