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The effects of methylmercury on motor activity are sex- and age-dependent, and modulated by genetic deletion of adenosine receptors and caffeine administration.
Toxicology. 2007 Nov 30; 241(3):119-33.T

Abstract

Adenosine and its receptors are, as part of the brain stress response, potential targets for neuroprotective drugs. We have investigated if the adenosine receptor system affects the developmental neurotoxicity caused by the fish pollutant methylmercury (MeHg). Behavioral outcomes of low dose perinatal MeHg exposure were studied in mice where the A(1) and A(2A) adenosine receptors were either partially blocked by caffeine treatment or eliminated by genetic modification (A(1)R and A(2A)R knock-out mice). From gestational day 7 to day 7 of lactation dams were administered doses that mimic human intake via normal diet, i.e. 1microM MeHg and/or 0.3g/l caffeine in the drinking water. This exposure to MeHg resulted in a doubling of brain Hg levels in wild type females and males at postnatal day 21 (PND21). Open field analysis was performed at PND21 and 2 months of age. MeHg caused time-dependent behavioral alterations preferentially in male mice. A decreased response to amphetamine in 2-month-old males pointed to disturbances in dopaminergic functions. Maternal caffeine intake induced long-lasting changes in the offspring evidenced by an increased motor activity and a modified response to psychostimulants in adult age, irrespectively of sex. Similar alterations were observed in A(1)R knock-out mice, suggesting that adenosine A(1) receptors are involved in the alterations triggered by caffeine exposure during development. Perinatal caffeine treatment and, to some extent, genetic elimination of adenosine A(1) receptors, attenuated the behavioral consequences of MeHg in males. Importantly, also deletion of the A(2A) adenosine receptor reduced the vulnerability to MeHg, consistent with the neuroprotective effects of adenosine A(2A) receptor inactivation observed in hypoxia and Parkinson's disease. Thus, the consequences of MeHg toxicity during gestation and lactation can be reduced by adenosine A(1) and A(2A) receptor inactivation, either via their genetic deletion or by treatment with their antagonist caffeine.

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Authors+Show Affiliations

Björklund O
Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Kahlström J
No affiliation info available
Salmi P
No affiliation info available
Ogren SO
No affiliation info available
Vahter M
No affiliation info available
Chen JF
No affiliation info available
Fredholm BB
No affiliation info available
Daré E
No affiliation info available

MeSH

AgingAnimalsBrainCaffeineEnvironmental PollutantsFemaleGene DeletionLactationMaleMaternal ExposureMethylmercury CompoundsMiceMice, KnockoutMotor ActivityPregnancyPurinergic P1 Receptor AntagonistsReceptors, Purinergic P1Sex Factors

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17920182

Citation

Björklund, Olga, et al. "The Effects of Methylmercury On Motor Activity Are Sex- and Age-dependent, and Modulated By Genetic Deletion of Adenosine Receptors and Caffeine Administration." Toxicology, vol. 241, no. 3, 2007, pp. 119-33.
Björklund O, Kahlström J, Salmi P, et al. The effects of methylmercury on motor activity are sex- and age-dependent, and modulated by genetic deletion of adenosine receptors and caffeine administration. Toxicology. 2007;241(3):119-33.
Björklund, O., Kahlström, J., Salmi, P., Ogren, S. O., Vahter, M., Chen, J. F., Fredholm, B. B., & Daré, E. (2007). The effects of methylmercury on motor activity are sex- and age-dependent, and modulated by genetic deletion of adenosine receptors and caffeine administration. Toxicology, 241(3), 119-33.
Björklund O, et al. The Effects of Methylmercury On Motor Activity Are Sex- and Age-dependent, and Modulated By Genetic Deletion of Adenosine Receptors and Caffeine Administration. Toxicology. 2007 Nov 30;241(3):119-33. PubMed PMID: 17920182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of methylmercury on motor activity are sex- and age-dependent, and modulated by genetic deletion of adenosine receptors and caffeine administration. AU - Björklund,Olga, AU - Kahlström,Johan, AU - Salmi,Peter, AU - Ogren,Sven Ove, AU - Vahter,Marie, AU - Chen,Jiang-Fan, AU - Fredholm,Bertil B, AU - Daré,Elisabetta, Y1 - 2007/08/31/ PY - 2007/05/12/received PY - 2007/07/15/revised PY - 2007/08/17/accepted PY - 2007/10/9/pubmed PY - 2007/12/27/medline PY - 2007/10/9/entrez SP - 119 EP - 33 JF - Toxicology JO - Toxicology VL - 241 IS - 3 N2 - Adenosine and its receptors are, as part of the brain stress response, potential targets for neuroprotective drugs. We have investigated if the adenosine receptor system affects the developmental neurotoxicity caused by the fish pollutant methylmercury (MeHg). Behavioral outcomes of low dose perinatal MeHg exposure were studied in mice where the A(1) and A(2A) adenosine receptors were either partially blocked by caffeine treatment or eliminated by genetic modification (A(1)R and A(2A)R knock-out mice). From gestational day 7 to day 7 of lactation dams were administered doses that mimic human intake via normal diet, i.e. 1microM MeHg and/or 0.3g/l caffeine in the drinking water. This exposure to MeHg resulted in a doubling of brain Hg levels in wild type females and males at postnatal day 21 (PND21). Open field analysis was performed at PND21 and 2 months of age. MeHg caused time-dependent behavioral alterations preferentially in male mice. A decreased response to amphetamine in 2-month-old males pointed to disturbances in dopaminergic functions. Maternal caffeine intake induced long-lasting changes in the offspring evidenced by an increased motor activity and a modified response to psychostimulants in adult age, irrespectively of sex. Similar alterations were observed in A(1)R knock-out mice, suggesting that adenosine A(1) receptors are involved in the alterations triggered by caffeine exposure during development. Perinatal caffeine treatment and, to some extent, genetic elimination of adenosine A(1) receptors, attenuated the behavioral consequences of MeHg in males. Importantly, also deletion of the A(2A) adenosine receptor reduced the vulnerability to MeHg, consistent with the neuroprotective effects of adenosine A(2A) receptor inactivation observed in hypoxia and Parkinson's disease. Thus, the consequences of MeHg toxicity during gestation and lactation can be reduced by adenosine A(1) and A(2A) receptor inactivation, either via their genetic deletion or by treatment with their antagonist caffeine. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/17920182/The_effects_of_methylmercury_on_motor_activity_are_sex__and_age_dependent_and_modulated_by_genetic_deletion_of_adenosine_receptors_and_caffeine_administration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(07)00614-2 DB - PRIME DP - Unbound Medicine ER -