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  • 1
    Electronic Resource
    Electronic Resource
    Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain (1994)
    Springer
    Journal of neural transmission 97 (1994), S. 135-147 
    Details
    ISSN: 1435-1463
    Keywords: Aging ; second messenger ; rolipram ; gerbil ; phosphodiesterase ; receptor autoradiography ; neurotransmitter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01277949
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  • 2
    Electronic Resource
    Electronic Resource
    Age-related changes of sodium-dependentd-[3H]aspartate and [3H]FK506 binding in rat brain (1997)
    Springer
    Journal of neural transmission 104 (1997), S. 259-267 
    Details
    ISSN: 1435-1463
    Keywords: Aging ; excitatory amino acid transport sites ; FK506 ; immunophilin ; receptor autoradiography ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated age-related changes in excitatory amino acid transport sites and FK506 binding protein (FKBP) in 3-week-, and 6-, 12-, 18- and 24-month-old Fischer 344 rat brains using receptor autoradiography. Sodium-dependentd-[3H]aspartate and [3H]FK506 were used to label excitatory amino acid transport sites and immunophilin (FKBP), respectively. In immature rats (3-week-old), sodium-dependentd-[3H]aspartate binding was lower in the frontal cortex, parietal cortex, striatum, nucleus accumbens, whole hippocampus, thalamus and cerebellum as compared to adult animals (6-month-old), whereas [3H]FK506 binding was significantly lower only in the hippocampus, thalamus and cerebellum. [3H]FK506 binding exhibited no significant change in the brain regions examined during aging. However, sodium-dependentd-[3H]aspartate binding showed a conspicuous reduction in the substantia nigra in 18-month-old rats. Thereafter, a significant reduction in sodium-dependentd-[3H]aspartate binding was found in the thalamus, substantia nigra and cerebellum in 24-month-old rats. Other regions also showed about 10–25% reduction in sodium-dependentd-[3H]aspartate binding. The results indicate that excitatory amino acid transport sites are more susceptible to aging process than immunophilin. Further, our findings demonstrate the conspicuous differences in the developmental pattern between excitatory amino acid transport sites and immunophilin in immature rat brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01273186
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  • 3
    Electronic Resource
    Electronic Resource
    Sequential changes of cholinergic and dopaminergic receptors in brains after 6-hydroxydopamine lesions of the medial forebrain bundle in rats (2000)
    Springer
    Journal of neural transmission 107 (2000), S. 873-884 
    Details
    ISSN: 1435-1463
    Keywords: Keywords: Cholinergic receptors ; high-affinity choline uptake sites ; dopamine D2 receptors ; receptor autoradiography ; 6-hydroxydopamine ; nigrostriatal pathway ; rat.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. We studied sequential changes in muscarinic cholinergic receptors, high-affinity choline uptake sites and dopamine D2 receptors in the brain after 6-hydroxydopamine lesions of the medial forebrain bundle in rats. The animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks postlesion. [3H]Quinuclidinylbenzilate (QNB), [3H]hemicholinum-3 (HC-3) and [3H]raclopride were used to label muscarinic cholinergic receptors, high-affinity choline uptake sites and dopamine D2 receptors, respectively. The degeneration of nigrostriatal pathway produced a transient decrease in [3H]QNB binding in the parietal cortex of both ipislateral and contralateral sides at 2 and 8 weeks postlesion. [3H] QNB binding also showed a mild but insignificant decrease in the ipsilateral striatum throughout the postlesion periods. No significant change was observed in the substantia nigra (SN) of both ipsilateral and contralateral sides throughout the postlesion periods. In contrast, [3H]HC-3 binding showed no significant change in the parietal cortex of both ipsilateral and contralateral sides during the postlesion. However, [3H]HC-3 binding was upregulated in the ipsilateral dorsolateral striatum throughout the postlesion periods. The ventromedial striatum also showed a significant increase in [3H]HC-3 binding at 1 week and 2 weeks postlesion. On the other hand, no significant change in [3H]raclopride binding was found in the parietal cortex of both ipsilateral and contralateral sides during the postlesion. [3H]Raclopride binding showed a conspicuous increase in the ipsilateral striatum (35–52% of the sham-operated values in the lateral part and 39–54% in the medial part) throughout the postlesion periods. In the contralateral side, a mild increase in [3H]raclopride binding was also found in the striatum (10–15% of the sham-operated values in the lateral part and 22% in the medial part) after lesioning. However, a significant decline in [3H]raclopride binding was observed in the ipsilateral SN and ventral tegmental area during the postlesion. The present study indicates that 6-hydroxydopamine injection of medial forebrain bundle in rats can cause functional changes in high-affinity choline uptake site in the striatum, as compared with muscarinic cholinergic receptors. Furthermore, our studies demonstrate an upregulation in dopamine D2 receptors in the striatum and a decrease in the receptors in the SN and ventral tegmental area after the 6-hydroxydopamine injection. Thus, these findings provide further support for neurodegeneration of the nigrostriatal pathway that occurs in Parkinson's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007020070039
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  • 4
    Electronic Resource
    Electronic Resource
    Long-term observations in gerbil brain following transient cerebral ischemia: Autoradiographic and histological study (1993)
    Springer
    Metabolic brain disease 8 (1993), S. 181-195 
    Details
    ISSN: 1573-7365
    Keywords: transient ischemia ; dopamine D1 ; naloxone ; forskolin ; receptor autoradiography ; gerbil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the long-term changes that occur in the gerbil brain following transient cerebral ischemia using histology and receptor autoradiography. Transient ischemia was induced for 3 and 10 min, and animals were allowed to survive for 8 months. A histological study showed that 3-min ischemia caused neuronal damage and mild atrophy only in the hippocampal CA1 sector, and that 10-min ischemia produced severe neuronal damage and marked shrinkage in the hippocampal CA1 and CA3 sectors. Furthermore, severe neuronal damage was seen in the striatum after 10-min ischemia. Autoradiography study revealed that 3-min ischemia caused a significant reduction in [3H] naloxone binding in the frontal cortex, striatum, dentate gyrus, and thalamus, whereas [3H]SCH 23390 and [3H] forskolin binding was not significantly altered in all regions, In contrast, 10-min ischemia produced marked alteration in these binding sites in the striatum, hippocampus, thalamus, and substantia nigra. The alteration was especially notable in the hippocampal region and substantia nigra. These results indicate that hippocampal damage after transient ischemia, compared with that in other regions, is not static, but particularly progressive. Furthermore, they demonstrate a reduction in adenylate cyclase system in the striatum and substantia nigra after transient ischemia. Moreover, our results suggest that long-term survival after ischemia may induce synaptic modification of neurotransmitter and adenylate cyclase system in the hippocampus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00996929
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  • 5
    Electronic Resource
    Electronic Resource
    Increases in [3H]FK-506 and [3H]L-NG-Nitro-Arginine Binding in the Rat Brain After Nigrostriatal Dopaminergic Denervation (1999)
    Springer
    Metabolic brain disease 14 (1999), S. 21-31 
    Details
    ISSN: 1573-7365
    Keywords: FK-506 ; immunophilin ; nitric oxide synthase ; dopamine uptake sites ; 6-hydroxydopamine ; receptor autoradiography ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Receptor autoradiographic technique was studied to investigate sequential changes in FK-506 binding proteins, nitric oxide synthase and dopamine uptake sites in the brain 1 week to 8 weeks after unilateral 6-hydroxydopamine injection of the medial forebrain bundle in rats. [3H]FK-506, [3H]L-NG-nitro-arginine and [3H]mazindol were used to label FK-506 binding proteins (immunophilin), nitric oxide synthase and dopamine uptake sites, respectively. [3H]FK-506 binding showed about 13-25% increase in the ipsilateral striatum from 2 to 8 weeks after degeneration of nigrostriatal pathway. However, no significant change in [3H]FK-506 binding was observed in the ipsilateral substantia nigra during the postlesion periods. In the contralateral side, [3H]FK-506 binding also showed about 13-25% increase in the striatum from 2 to 8 weeks postlesion. The substantia nigra showed a 21% increase in [3H]FK-506 binding only 2 weeks after the lesioning. On the other hand, [3H]L-NG-nitro-arginine binding showed about 21-31% increase in the parietal cortex and striatum 1 week or 2 weeks postlesion. In the contralateral side, a 21% increase in [3H]L-NG-nitro-arginine binding was found in the dorsolateral striatum only 1 week postlesion. In contrast, degeneration of nigrostriatal pathway caused a conspicuous loss of [3H]mazindol binding in the ipsilateral striatum (87-96%), substantia nigra (36-73%) and ventral tegmental area (91-100%) during the postlesion periods. In the contralateral side, no significant changes in [3H]mazindol binding were observed in these areas upto 8 weeks after the postlesion. The present study demonstrates that unilateral injection of 6-hydroxydopamine into the medial forebrain bundle of rats can cause a significant increase in [3H]FK-506 and [3H]L-NG-nitro-arginine bindings in the brains. In contrast, a marked reduction in [3H]mazindol binding is observed in the brains after the lesioning, indicating severe damage to nigrostriatal dopaminergic pathway. These results suggest that immunophilin and nitric oxide synthase may play some role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020605429535
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