کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998279 | 1115618 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
To evaluate the consequences of inactivation of the serotonin transporter (SERT) gene on 5-HT homeostasis and function, 5-HT synthesis and turnover rates were measured using the decarboxylase inhibition method in multiple brain regions (frontal cortex, striatum, brainstem, hippocampus and hypothalamus) from mice with a genetic disruption of SERT. 5-HT synthesis rates were increased 30-60% in the different brain regions of SERT â/â mice compared to littermate +/+ control mice despite 55-70% reductions in tissue 5-HT concentrations. Brain regions that possessed a greater capacity to increase synthesis and turnover (frontal cortex, striatum) demonstrated lesser reductions in tissue 5-HT. Female SERT â/â mice had greater increases (79%) in brain 5-HT synthesis than male â/â mice did (25%), a finding associated with higher brain tryptophan concentrations in females. Despite increased 5-HT synthesis, there was no change in either TPH2 or TPH1 mRNA levels or in maximal in vitro TPH activity in the brainstem of SERT â/â mice. Catecholamine homeostasis as reflected in brain tissue concentrations and in synthesis and turnover of dopamine and norepinephrine was unchanged in SERT â/â mice. Taken together, the results demonstrate a markedly altered homeostatic situation in SERT â/â mice that lack 5-HT reuptake, resulting in markedly depleted tissue stores that are inadequately compensated for by increased 5-HT synthesis, with brain region and gender specificity observed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 49, Issue 6, November 2005, Pages 798-810
Journal: Neuropharmacology - Volume 49, Issue 6, November 2005, Pages 798-810
نویسندگان
Dong-Kyu Kim, Teresa J. Tolliver, Su-Jan Huang, Bradley J. Martin, Anne M. Andrews, Christine Wichems, Andrew Holmes, Klaus-Peter Lesch, Dennis L. Murphy,