Postmortem stability of monoamines, their metabolites, and receptor binding in rat brain regions

Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Journal of Neurochemistry (Impact Factor: 4.28). 02/1994; 62(1):282-90.
Source: PubMed


The effects of postmortem delay, time of storage, and freezing, thawing, and refreezing tissue samples were studied in postmortem rat brain using conditions that reflect the handling of postmortem human brain before neurochemical analysis. The levels of monoamines and metabolites in the striatum and cingulate and occipital cortex were measured using alumina extraction and HPLC methods. Binding of raclopride to dopamine D2, SCH-23390 to dopamine D1, ketanserin to serotonin 5-HT2, 8-hydroxy-2-(di-n-propylamino)tetralin to serotonin 5-HT1A, and cholecystokinin (CCK)-8 to CCK-B sites was measured in tissue homogenates from the striatum or fronto-parietal cortex. An 18-h postmortem delay before dissection and storage resulted in region-specific changes in monoamine and metabolite levels. Binding to striatal D1 and frontoparietal cortex CCK-B sites was reduced over the course of a 27-h postmortem delay. Binding to D2 and 5-HT sites was relatively stable. Storage of tissue for up to 8 months also resulted in region-specific changes in monoamine and metabolite levels. No changes in receptor binding were seen after long-term storage. Freezing, thawing, and refreezing tissue samples resulted in increased levels of striatal 3,4-dihydroxyphenylacetic acid and decreased binding to striatal D2 sites. These results demonstrate time-, temperature-, and storage-dependent regional differences in the stability of monoamines and their metabolites and in binding to various receptor sites. These differences in stability and binding should be accounted for to interpret accurately the effects of neurological disorders on neurotransmitter dynamics in postmortem human brain tissue.

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    • "The suicide group in our study has a 1.9 h shorter mean PMI than controls, which was not statistically different and does not likely explain the differences between groups in 5-HT or 5-HIAA. Postmortem studies report that 5- HT decreases initially (Kontur et al., 1994; McIntyre and Stanley, 1984; Palmer et al., 1988) and is largely stable thereafter; 5-HIAA was reported to either increase or remain unchanged. Therefore, the 5-HT and 5-HIAA measures with the 6–22 h range of PMIs in our study are likely stable. "
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    ABSTRACT: Using high pressure liquid chromatography, we find more brainstem 5‐HT and 5‐HIAA in suicides compared with nonpsychiatric, sudden death controls throughout the rostrocaudal extent of the brainstem DRN and MRN. This suggests that 5‐HT synthesis in suicides is greater within all DRN subnuclei and the MRN compared with controls.
    Synapse 03/2014; 68(3). DOI:10.1002/syn.21695 · 2.13 Impact Factor
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    • "Two of the subjects were males, 2 were females; the mean age was 75 years (age range from 72 to 77 years). The post-mortem delay was between 8 and 13 h, which is well within the published limits of sufficient receptor stability (Kontur et al. 1994). Because fixation would alter structure and hence binding characteristics of receptor molecules, the whole native hemispheres were dissected into 6 slabs, each of which was shock frozen at –40 °C and stored at –70 °C. "
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    ABSTRACT: This receptorarchitectonic study of the human visual cortex investigated interareal differences in mean receptor concentrations and laminar distribution patterns of 16 neurotransmitter receptors in the dorsal and ventral parts of areas V1, V2, V3 as well as in adjoining areas V4 (ventrally) and V3A (dorsally). Both the functional hierarchy of these areas and a distinction between dorsal and ventral visual cortices were reflected by significant receptorarchitectonic differences. The observation that dorso-ventral differences existed in all extrastriate areas (including V2) is particularly important for the discussion about the relationship between dorsal and ventral V3 as it indicates that a receptorarchitectonic distinction between the ventral and dorsal visual cortices is present in but not specific to V3. This molecular specificity is mirrored by previously reported differences in retinal microstructure and functional differences as revealed in behavioral experiments demonstrating differential advantages for stimulus processing in the upper and lower visual fields. We argue that these anatomical and functional differences may be regarded as the result of an evolutionary optimization adapting to the processing of the most relevant stimuli occurring in the upper and lower visual fields.
    Cerebral Cortex 04/2008; 18(11):2637-45. DOI:10.1093/cercor/bhn024 · 8.67 Impact Factor
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    • "Two of the subjects were males; the mean age was 75 years (age-range from 72–77 years). The post-mortem delay was between 8 and 13 h for all cases, which is well within the published limits of sufficient receptor stability (Kontur et al. 1994). Since fixation would alter the structure of receptor molecules and hence their binding characteristics, the whole native hemispheres were dissected into six slabs, frozen and stored at –70°C. "
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    ABSTRACT: The laminar distributions of 16 neurotransmitter receptor binding sites were analysed in visual cortical areas V1-V3 by quantitative in vitro receptor autoradiography. For each receptor (glutamatergic: AMPA, kainate, NMDA; cholinergic: M1, M2, M3, nicotinic; GABAergic: GABAA, GABAB, benzodiazepine binding-sites; adrenergic: alpha1, alpha2; serotoninergic: 5-HT1A, 5-HT2; dopaminergic: D1; Adenosine: A1), density profiles extracted perpendicular to the cortical surface were compared to cyto- and myeloarchitectonic profiles sampled at corresponding cortical sites. When testing for differences in laminar distribution patterns, all receptor-density profiles differed significantly from the cyto- and myeloarchitectonic ones. These results indicate that receptor distribution is an independent feature of the cortical architecture not predictable by densities of cell bodies or myelinated fibres. Receptor co-distribution was studied by cluster analyses, revealing several groups of receptors, which showed similar laminar distribution patterns across all analysed areas (V1-V3). Other receptors were co-distributed in extrastriate but not primary visual cortex. Finally, some receptors were not co-distributed with any of the analysed other ones. A comparison of the laminar patterns of receptor binding sites in the human visual cortex with those reported for non-human primates and other mammals showed that the laminar distributions of cholinergic and glutamatergic receptors seem largely preserved, while serotoninergic and adrenergic receptors appear to be more variable between different species.
    Brain Structure and Function 01/2008; 212(3-4):255-67. DOI:10.1007/s00429-007-0156-y · 5.62 Impact Factor
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