1,721,057 research outputs found

    Neurotransmitters, neuroreceptors and aging.

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    At first glance, it is satisfying to see the progress which has been made in the study of neurotransmitters. We have learned a great deal in the last number of years. First, we have been able to identify previously unknown compounds which affect the nervous system or associated peripheral organs. We now know a great deal about the metabolism of these molecules including their synthesis and catabolism. We have learned to identify and to classify their receptors. We have learned that alterations in the effects of neurotransmitters may be responsible for certain pathologies or may be a function of normal aging. Yet, we still have far to go in our research. There are neurotransmitters still to be discovered. We need to continue our efforts because there is still a large amount of confusion in the literature, for example, far too many contradictory reports concerning the effects of age confuse rather than clarify. Possibly order may return to the literature if investigators can agree on some basic tenets. For example, we need a basic definition of old. Some research groups consider 12-month-old rats as old while other groups consider them to be young individuals. We need to have standardization of methodology so that the conclusions can have validity. Once again certain investigators use whole brain homogenates while others use only discrete portions. We need to consider whether the effect we see in our experiment is primary or secondary to aging. We can be certain that due to the aging population, the importance of basic research of age-dependent changes in neurotransmitters and neuroreceptors will increase in the future

    Dopamine receptors in the rat thymus.

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    Radioreceptor assay and autoradiographic techniques with 3H-SCH 23390 as a ligand were used to characterize pharmacologically and to localize anatomically dopamine D-1 receptor sites in sections of rat thymus. 3H-SCH 23390 was specifically bound to sections of rat thymus in a manner consistent with the labeling of D-1 receptor sites. Autoradiography demonstrated the accumulation of 3H-SCH 23390 binding sites in the cortex of the thymus rather than in corpuscles

    NEURONAL APOLIPOPROTEIN J IS UP-REGULATED BY OXIDATIVE STRESS

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    Apolipoprotein J / clusterin (apoJ) is a multifunctional glycoprotein up-regulated during various pathophysiological states and might represent a defence mechanism during cellular damage. An increase in either apoJ mRNA or protein expression is observed in numerous neurodegenerative conditions including Alzheimer’s disease, Parkinson’ disease, Pick disease, amyotrophic lateral sclerosis, and Huntington disease. Furthermore, these neurodegenerative disorders are characterized by intraneuronal abnormal filament accumulation associated with markers of oxidative injury. To determine whether apoJ is affected by oxidative stress, we evaluated the effects of oxidative insult on the expression of apoJ as part of a cellular response in viable human neuroblastoma IMR-32 cells. In our experimental model iron-ascorbate induced oxidative stress in IMR-32 cells without affecting cell viability, as detected by MTT-assay. It was found that IMR-32 cells express apoJ mature protein and that oxidative stress induced an up-regulation of apoJ level revealed by immunoblot analysis. The results of the present study suggest that an increase in apoJ expression may be a physiological defence able to reduce cell damage and maintain cell viability during periods of increased radical production. Supported by the University of Bologna, Funds for Selected Research Topics

    Pharmacological characterization and autoradiographic localization of dopamine receptors in the rat adrenal medulla.

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    The pharmacological profile and the anatomical localization of dopamine D1-like and D2-like receptors were studied in sections of rat adrenal medulla, with radioligand binding and autoradiographic techniques, respectively. [3H]([R]-(+)-chloro-2,3,4,5-tetrahydro-5-phenyl-1 H-3benzazepin-al hemimaleate) (SCH 23390) was used as a ligand for dopamine D1-like receptors and [3H]spiperone was used as a ligand for dopamine D2-like receptors. Radioligand binding and light microscope autoradiography did not show specific [3H]SCH 23390 binding in sections of rat adrenal medulla. This suggests that rat adrenal medulla does not express dopamine D1-like receptors. [3H]Spiperone was specifically bound to sections of rat adrenal medulla. The binding was time-, temperature- and concentration-dependent, with a dissociation constant (Kd) of 1.05 nM and a maximum density of binding sites (Bmax) of 100.2 +/- 3.8 fmol/mg tissue. The pharmacological profile of [3H]spiperone binding to rat adrenal medulla was similar to that displayed by neostriatum, which is known to express dopamine D2 receptors. Light microscope autoradiography showed the accumulation of specifically bound [3H]spiperone as silver grains within sections of adrenal medulla. Silver grains were found primarily over the cellular membrane of chromaffin cells. The above data indicate that chromaffin cells of the rat adrenal medulla express dopamine receptors belonging to the dopamine D2 receptor subtype. These receptors are probably involved in the modulation of catecholamine release from chromaffin cells, as documented by functional studies

    Identification of age-related changes of dopamine D1-like receptors in the rat cerebellar cortex.

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    The present study was designed to characterize the pharmacological profile of dopamine D1-like receptors in the rat cerebellar cortex and to assess if these receptor sites undergo age-related changes. Cerebella of young (3 months), adult (12 months), and old (27 months) male Wistar rats were examined by using radioligand binding techniques and light microscope autoradiography. The non-selective dopamine D1-like radioligand [3H]SCH 23390 was specifically bound to sections of rat cerebellum. The findings that dopamine displaced [3H]SCH 23390 binding in the submicromolar range suggest that labelling of a dopamine D5 (or D1B) receptor subtype. The affinity of [3H]SCH 23390 for dopamine D1-like receptors was similar in the cerebellar cortex of the three animal groups investigated, whereas radioligand binding techniques revealed a gradual age-related reduction of the density of binding sites. Light microscope autoradiography showed the localization of [3H]SCH 23390 binding sites primarily in the molecular layer and to a lesser extent in the Purkinje neuron layer of the cerebellar cortex. Aging was accompanied by a loss of [3H]SCH 23390 binding sites affecting mainly the molecular layer. The age-dependent loss of dopamine D1-like receptors is more pronounced if detected with radioligand binding techniques than with light microscope autoradiography. This suggests that the decrease of dopamine D1-like receptors observed in aging rat cerebellar cortex may depend in part on changes in the receptor expression and in part on cortico-cerebellar structural changes

    Muscarinic cholinergic receptors in the hippocampus of aged rats: influence of choline alphoscerate treatment.

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    The present study was designed to investigate age-dependent changes of muscarcinic M1 and M2 cholinergic receptors in the rat hippocampus using radioreceptor assay and autoradiographic techniques with [3H]pirenzepine and [3H]AF-DX 116 as ligands. The analysis was performed on 2-, 12- and 27-month-old male Wistar rats, considered young, adult and old, respectively. Moreover, the influence of a 6-month treatment with choline alphoscerate on the density and pattern of M1 and M2 cholinergic receptors was assessed. Choline alphoscerate (L-alpha-glyceryl phosphorylcholine) is a precursor in the biosynthesis of several brain phospholipids which increases the availability of acetylcholine in various tissues. Muscarinic M1 cholinergic receptors were significantly decreased with increasing age whereas M2 cholinergic receptors did not show changes. Choline alphoscerate treatment countered, in part, the loss of muscarinic M1 receptor sites in old rats. Light microscope autoradiography revealed a loss of silver grains developed after exposure of sections of hippocampus to [3H]pirenzepine in the stratum oriens of CA1 and CA3 fields in rats of 12 and 27 months in comparison with young animals. Choline alphoscerate restored, in part, the decrease of silver grains noted in old rats. Quantitative analysis of the density of silver grains developed in the cell body of pyramidal neurons of CA1 and CA3 fields processed for the demonstration of muscarinic M1 receptor sites revealed a decrease of these grains in rats of 27 months in comparison with younger cohorts. These findings suggest that the reduction in muscarinic M1 sites noticeable between 2- and 12-month rats is probably dependent on the loss of nerve cells and/or terminals in these hippocampal fields rather than to a reduction of their density per neuron. Treatment with choline alphoscerate increased the expression of muscarinic M1 cholinergic receptors within the cell body of pyramidal neurons of CA1 and CA3 fields compared to age-matched control old rats. Consistent with radioreceptor assay data, no changes in the density of muscarinic M2 cholinergic receptors in the animal groups examined were demonstrated by light microscope autoradiography. The possible pharmacological relevance of the increased expression of muscarinic M1 cholinergic receptors elicited by choline alphoscerate in the hippocampus of aged rats is discussed
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