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Region-Specific and...
Region-Specific and Age-Dependent Multitarget Effects of Acetylcholinesterase Inhibitor Tacrine on Comprehensive Neurotransmitter Systems
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- Fridjonsdottir, Elva (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Vallianatou, Theodosia (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Mantas, Ioannis (author)
- Karolinska Institutet
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- Shariatgorji, Reza (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Nilsson, Anna (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Schembri, Luke S (author)
- Uppsala universitet,Preparativ läkemedelskemi
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- Odell, Luke R. (author)
- Uppsala universitet,Preparativ läkemedelskemi
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- Svenningsson, Per (author)
- Karolinska Institutet
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- Andrén, Per E., Professor, 1957- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- 2021-12-21
- 2022
- English.
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In: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 17:1, s. 147-158
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Abstract
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- Regional brain distribution and metabolism of neurotransmitters and their response to drug treatment are fundamentally important for understanding the central effects of neuroactive substances. We used matrix-assisted laser desorption/ionization mass spectrometry imaging in combination with multivariate analysis to visualize in anatomical detail metabolic effects of aging and tacrine-mediated acetylcholinesterase inhibition on comprehensive neurotransmitter systems in multiple mouse brain regions of 12-week-old and 14-month-old mice. We detected age-related increases in 3,4-dihydroxyphenylacetaldehyde and histamine, indicating oxidative stress and aging deficits in astrocytes. Tacrine had a significant impact on the metabolism of neurotransmitters in both age groups; predominantly, there was an increased norepinephrine turnover throughout the brain and decreased 3-methoxy tyramine, a marker for dopamine release, in the striatum. The striatal levels of histamine were only elevated after tacrine administration in the older animals. Our results demonstrated that tacrine is a multitarget and region-specific neuroactive agent, inducing age-specific responses. Although well-studied, the complete mechanisms of the action of tacrine are not fully understood, and the current findings reveal features that may help explain its treatment-related effectiveness and central side effects.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- ref (subject category)
- art (subject category)
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Fridjonsdottir, ...
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Vallianatou, The ...
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Mantas, Ioannis
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Shariatgorji, Re ...
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Nilsson, Anna
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Schembri, Luke S
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Odell, Luke R.
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Svenningsson, Pe ...
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Andrén, Per E., ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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ACS Chemical Bio ...
- By the university
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Uppsala University
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Karolinska Institutet