ABSTRACT
There are discrepancies in the literature about the effects of aging on NMDA receptor expression in the hippocampus. The present study was designed to determine whether there are regional differences in how NMDA receptors are affected by aging. Brains from male C57BL/6 mice from three different age groups (3, 10, and 30 months of age) were sectioned coronally through the dorsal hippocampus and horizontally through the intermediate hippocampus. Sections were processed and analyzed for [3H]glutamate binding to NMDA receptors using receptor autoradiography and for mRNA for the zeta1 (NR1), epsilon1 (NR2A), and epsilon2 (NR2B) subunits of the NMDA receptor using in situ hybridization. There were more significant effects of aging within the intermediate hippocampus in NMDA-displaceable [3H]glutamate binding and epsilon2 mRNA densities than were seen in the dorsal hippocampus. There was no significant effect of age on densities of either the zeta1 or epsilon1 subunit mRNA. These results suggest that the aging process affects NMDA receptors more in the intermediate hippocampus than the dorsal.
Subject(s)
Aging/metabolism , Gene Expression Regulation/physiology , Hippocampus/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Age Factors , Analysis of Variance , Animals , Autoradiography/methods , Glutamic Acid/pharmacokinetics , Hippocampus/anatomy & histology , Hippocampus/drug effects , In Situ Hybridization/methods , Male , Mice , Mice, Inbred C57BL , Protein Subunits/genetics , Protein Subunits/metabolism , Receptors, N-Methyl-D-Aspartate/classification , Receptors, N-Methyl-D-Aspartate/genetics , Tritium/pharmacokineticsABSTRACT
OBJECTIVE: To test the hypothesis that the distribution, density, and subtype of opioid and alpha (alpha)-2 adrenergic receptors within the central nervous system (CNS) are significantly different between horse and dog. STUDY DESIGN: Prospective experimental study. ANIMALS: Three dogs (3 years of age) and three horses (2-5 years of age). Animals were opioid- and alpha-2 agonist-free at the time of euthanasia. METHODS: Brain tissue was obtained at 126 days post-surgery from dogs and 72 days post-surgery from horses. The brains were removed, sectioned coronally into 1-cm slabs, frozen in methylbutane, which was cooled by liquid nitrogen, and stored at -70 degrees C. Receptor autoradiography was performed using established techniques. [3H]DAMGO, [3H]U-69593, and [3H]RX821002 were used for mu ( micro )-opioid, kappa (kappa)-opioid, and alpha-2 adrenergic-binding assays, respectively. Species differences were analyzed separately for each major brain region by repeated measures anova for subregions followed by Fisher's protected Latin square design (LSD). p < 0.05 was considered significant. RESULTS: There was higher binding of micro -opioid receptors in the frontal cortex, left somatosensory cortex, colliculus (mid-brain), and granule cell layer of the cerebellum of horses than that of dogs. There was higher binding to kappa-opioid receptors in the frontal cortex of dogs compared to horses, whereas binding to kappa-opioid receptors in the cerebellum was higher in horses. Binding to alpha-2 adrenergic receptors in the mid-brain was significantly higher in dogs than in horses. There was higher binding of alpha-2 adrenergic receptors in the dorsomedial and dorsolateral periaqueductal grey of dogs as compared to that of horses. CONCLUSION: The results of this study show that the distribution of these receptors is different between horses and dogs. Further work is needed to understand the relevance of these differences to clinical responses to opioids and alpha-2 adrenergic agonists in these species.
