scholarly journals Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA–induced dyskinesia

2021 ◽  
Vol 7 (2) ◽  
pp. eabe5948
Author(s):  
Elva Fridjonsdottir ◽  
Reza Shariatgorji ◽  
Anna Nilsson ◽  
Theodosia Vallianatou ◽  
Luke R. Odell ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Side Effects ◽  
Mass Spectrometry Imaging ◽  
Brain Regions ◽  
Stria Terminalis ◽  
Brain Areas ◽  
Bed Nucleus ◽  
Neuronal Signaling ◽  
Cortical Areas ◽  
The Brain

l-DOPA treatment for Parkinson’s disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA–induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.

Effect of Inhibition of the Central Nucleus of the Amygdala and Drug Experience on the Regions Underlying Footshock-Induced Reinstatement of Morphine Seeking

2008 ◽  
Vol 36 (5) ◽  
pp. 992-1000 ◽  
Author(s):  
DY Ma ◽  
MY Xu ◽  
HC Yang ◽  
LZ Yang
Keyword(s):  
Interactive Effect ◽  
Brain Regions ◽  
Place Preference ◽  
Central Nucleus ◽  
Stria Terminalis ◽  
Drug Experience ◽  
Bed Nucleus ◽  
Fos Expression ◽  
The Difference ◽  
The Brain

This study assessed the effect of inhibition of the central nucleus of the amygdala (CeA) and drug experience on brain regions underlying footshock-induced reinstatement of morphine-seeking behaviour in rats. The difference in time spent in two chambers of a place-preference apparatus was used to measure morphine-conditioned place preference. Fos was measured as a marker of neuronal activation in the ventral bed nucleus of the stria terminalis (BNSTv) and ventral tegmental area (VTA). Footshock was found to enhance Fos expression in the BNSTv regardless of drug experience. In the VTA, morphine and footshock had an interactive effect on the increase in Fos expression. Inhibition of the CeA decreased Fos expression in the BNSTv regardless of drug experience, whereas in the VTA this effect only occurred in morphine-treated rats. These results suggest that drug experience has no differential effect on the BNSTv however morphine produces footshock sensitization in the VTA. CeA inhibition modulates the footshock-induced activity of these regions of the brain and attenuates reinstatement of drug seeking behaviour.

scholarly journals Mass Spectrometry Imaging for Glycome in the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Md. Mahmudul Hasan ◽  
Mst. Afsana Mimi ◽  
Md. Al Mamun ◽  
Ariful Islam ◽  
A. S. M. Waliullah ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Imaging Techniques ◽  
Enzymatic Digestion ◽  
Brain Regions ◽  
Enzymatic System ◽  
Biological Processes ◽  
Label Free ◽  
Post Translational Modification ◽  
The Brain

Glycans are diverse structured biomolecules that play crucial roles in various biological processes. Glycosylation, an enzymatic system through which various glycans are bound to proteins and lipids, is the most common and functionally crucial post-translational modification process. It is known to be associated with brain development, signal transduction, molecular trafficking, neurodegenerative disorders, psychopathologies, and brain cancers. Glycans in glycoproteins and glycolipids expressed in brain cells are involved in neuronal development, biological processes, and central nervous system maintenance. The composition and expression of glycans are known to change during those physiological processes. Therefore, imaging of glycans and the glycoconjugates in the brain regions has become a “hot” topic nowadays. Imaging techniques using lectins, antibodies, and chemical reporters are traditionally used for glycan detection. However, those techniques offer limited glycome detection. Mass spectrometry imaging (MSI) is an evolving field that combines mass spectrometry with histology allowing spatial and label-free visualization of molecules in the brain. In the last decades, several studies have employed MSI for glycome imaging in brain tissues. The current state of MSI uses on-tissue enzymatic digestion or chemical reaction to facilitate successful glycome imaging. Here, we reviewed the available literature that applied MSI techniques for glycome visualization and characterization in the brain. We also described the general methodologies for glycome MSI and discussed its potential use in the three-dimensional MSI in the brain.

scholarly journals Visualising Cholesterol in Brain by On-Tissue Derivatisation and Quantitative Mass Spectrometry Imaging

2020 ◽  
Author(s):  
Roberto Angelini ◽  
Eylan Yutuc ◽  
Mark F Wyatt ◽  
Jillian Newton ◽  
Fowzi Adam Yusuf ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Brain Structures ◽  
Brain Regions ◽  
Null Mouse ◽  
Brain Health ◽  
Quantitative Mass Spectrometry ◽  
Tissue Sections ◽  
Niemann Pick ◽  
The Brain

SummaryDespite being a critical molecule for neurobiology and brain health, mass spectrometry imaging (MSI) of cholesterol has been under reported compared to other lipids, due to the difficulty in ionising the sterol molecule. In the present work we have employed an on-tissue enzyme-assisted derivatisation strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific brain structures of the mouse brain, in a model of Niemann-Pick type C1 (NPC1) disease, and during brain development. MSI revealed how cholesterol changes during development and that in the adult is highest in pons and medulla of the brain stem. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience.

Engaging regularly with fiction influences connectivity in cortical areas for language and mentalizing

2017 ◽  
Author(s):  
Roel M. Willems ◽  
Franziska Hartung
Keyword(s):  
Functional Connectivity ◽  
Time Course ◽  
Language Skills ◽  
Brain Regions ◽  
Brain Areas ◽  
Daily Lives ◽  
Cortical Areas ◽  
Social Abilities ◽  
Behavioral Evidence ◽  
Amount Of Reading

Behavioral evidence suggests that engaging with fiction is positively correlated with social abilities. The rationale behind this link is that engaging with fictional narratives offers a ‘training modus’ for mentalizing and empathizing. We investigated the influence of the amount of reading that participants report doing in their daily lives, on connections between brain areas while they listened to literary narratives. Participants (N=57) listened to two literary narratives while brain activation was measured with fMRI. We computed time-course correlations between brain regions, and compared the correlation values from listening to narratives to listening to reversed speech. The between-region correlations were then related to the amount of fiction that participants read in their daily lives. Our results show that amount of fiction reading is related to functional connectivity in areas known to be involved in language and mentalizing. This suggests that reading fiction influences social cognition as well as language skills.

scholarly journals Transcriptomic, peptidomic and mass spectrometry imaging analysis of the brain in the ant Cataglyphis nodus

2021 ◽  
Author(s):  
Jens Habenstein ◽  
Franziska Schmitt ◽  
Sander Liessem ◽  
Alice Ly ◽  
Dennis Trede ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Imaging Analysis ◽  
The Brain

scholarly journals Imaging Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism

2018 ◽  
Author(s):  
Eylan Yutuc ◽  
Roberto Angelini ◽  
Mark Baumert ◽  
Natalia Mast ◽  
Irina Pikuleva ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Brain ◽  
Brain Function ◽  
Mass Spectrometry Imaging ◽  
Cholesterol Metabolism ◽  
Biologically Active ◽  
Wild Type ◽  
Tissue Slices ◽  
The Brain

AbstractDysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400 µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.SignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 µm resolution on 10 µm tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.

Transsexualism

2011 ◽  
pp. 1463-1468
Author(s):  
Louis J. G. Gooren
Keyword(s):  
Sexual Differentiation ◽  
External Genitalia ◽  
The Other ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Psychological Phenomenon ◽  
Opposite Sex ◽  
Male To Female ◽  
The Brain

Transsexualism is the condition in which a person with apparently normal somatic sexual differentiation is convinced that he/she is actually a member of the opposite sex. It is associated with an irresistible urge to be hormonally and surgically adapted to that sex. Traditionally transsexualism has been conceptualized as a purely psychological phenomenon, but research on the brains of male-to-female transsexuals has found that the sexual differentiation of the brain—the bed nucleus of the stria terminalis (BSTC) and the hypothalamic uncinate nucleus—had followed a female pattern (1). This finding may lead to a concept of transsexualism as a form of intersex, where the sexual differentiation of the brain (which in mammals also undergoes sexual differentiation) is not consistent with the other variables of sex, such as chromosomal pattern, nature of the gonad and nature of internal/external genitalia. Thus it can be argued that transsexualism is a sexual differentiation disorder.

Differential recovery of acetylcholinesterase in guinea pig muscle and brain regions after soman treatment

1998 ◽  
Vol 17 (3) ◽  
pp. 157-162 ◽  
Author(s):  
Maxine C Lintern ◽  
Janet R Wetherell ◽  
Margaret E Smith
Keyword(s):  
Enzyme Activity ◽  
Time Course ◽  
Brain Regions ◽  
Similar Rate ◽  
Molecular Forms ◽  
Similar Degree ◽  
Brain Areas ◽  
Pig Muscle ◽  
Rate Of Recovery ◽  
The Brain

1 In brain areas of untreated guinea-pigs the highest activity of acetylcholinesterase was seen in the striatum and cerebellum, followed by the midbrain, medulla-pons and cortex, and the lowest in the hippocampus. The activity in diaphragm was sevenfold lower than in the hippocampus. 2 At 1 h after soman (27 mg/kg) administration the activity of the enzyme was dramatically reduced in all tissues studied. In muscle the three major molecular forms (A12, G4 and G1) showed a similar degree of inhibition and a similar rate of recovery and the activity had returned to normal by 7 days. 3 In the brain soman inhibited the G4 form more than the G1 form. The hippocampus, cortex and midbrain showed the greatest reductions in enzyme activity. At 7 days the activity in the cortex, medulla pons and striatum had recovered but in the hippocampus, midbrain and cerebellum it was still inhibited. 4 Thus the effects of soman administration varied in severity and time course in the different tissues studied. However the enzyme activity was still reduced in all tissues at 24 h when the overt signs of poisoning had disappeared.

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