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Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain

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Summary

Age-related alterations in binding sites of major second messengers and a selective adenosine 3′,5′-cyclic monophosphate (cyclic-AMP) phospho-diesterase (PDE) in the gerbil brain were analysed by receptor autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]inositol 1,4,5-trisphosphate (IP3), [3H]forskolin, [3H]cyclic-AMP, and [3H]rolipram were used to label protein kinase C (PKC), IP3 receptor, adenylate cyclase, cyclic-AMP dependent protein kinase (PKA), and Ca2+/calmodulin-mdependent cyclic-AMP PDE, respectively. In middle-aged gerbils (16 months old), [3H]PDBu binding was significantly reduced in the hippocampal CA 1 sector, thalamus, substantia nigra, and cerebellum, compared with young animals (1 month old). [3H]IP3 binding revealed significant elevations in the nucleus accumbens, hippocampal CA 1 sector, dentate gyrus, and a significant reduction in cerebellum of middle-aged gerbils. [3H]Forskolin binding in middle-aged animals was significantly increased in the nucleus accumbens and hilus of dentate gyrus, but was diminished in the substantia nigra and cerebellum. On the other hand, in middle-aged animals, [3H]cyclic-AMP binding revealed a significant elevation only in the hippocampal CA3 sector, whereas [3H] rolipram binding showed a significant reduction in the thalamus and cerebellum. Thus, the age-related alteration in these binding sites showed different patterns among various brain regions in middle-aged gerbils indicating that the binding sites of PKC, IP3, and adenylate cyclase are more markedly affected by aging than those of PKA and cyclicAMP PDE and that the hippocampus and cerebellum are more susceptible to these aging processes than other brain regions. The findings suggest that in-tracellular signal transduction is affected at an early stage of senescence and this may lead to neurological deficits.

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  1. T. Araki

    Present address: Pharmacological Research Laboratory, Research Laboratories, Tokyo Tanabe Co. Ltd., Tokyo

Authors and Affiliations

  1. Department of Neurology, Institute of Brain Diseases, Tohoku University School of Medicine, Sendai

    T. Araki & H. Kato

  2. Pharmacological Research Laboratory, Research Laboratories, Tokyo Tanabe Co. Ltd., Tokyo

    Y. Kanai

  3. Foundation for Brain and Nerve Diseases and the Institute of Neuropathology, Kumagaya, Japan

    K. Kogure

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Araki, T., Kato, H., Kanai, Y. et al. Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain. J. Neural Transmission 97, 135–147 (1994). https://doi.org/10.1007/BF01277949

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  • DOI: https://doi.org/10.1007/BF01277949

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