scholarly journals Complete Spatial Characterisation of N-glycosylation upon Striatal Neuroinflammation in the Rodent Brain

2021 ◽  
Author(s):  
Ana Lúcia Rebelo ◽  
Francesco Gubinelli ◽  
Pauline Roost ◽  
Caroline Jan ◽  
Emmanuel Brouillet ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Multifaceted Approach ◽  
Brain Hemispheres ◽  
Adult Rat ◽  
Positron Emission ◽  
Ionisation Mass Spectrometry ◽  
Adult Rat Brain ◽  
The Central Nervous System ◽  
First Time

Abstract Background: Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended. A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e. post-translational addition of glycans to the protein structure). N- glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation. Changes in N- glycosylation can ultimately affect glycoproteins' functions, which will have an impact on cell machinery. Therefore characterisation of N- glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies. Methods: With that aim, the unilateral intrastriatal injection of Lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation. In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N- glycome was performed at one-week post-injection of LPS. These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI). Results: In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N- glycans were significantly increased (13.5%). This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N- glycans allowing precise comparison between normal and diseased brain hemispheres. Conclusions: Together, our data show for the first time the complete profiling of N- glycomic changes in a well-characterised animal model of neuroinflammation. These data represent a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases.

scholarly journals Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ana Lúcia Rebelo ◽  
Francesco Gubinelli ◽  
Pauline Roost ◽  
Caroline Jan ◽  
Emmanuel Brouillet ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Multifaceted Approach ◽  
Brain Hemispheres ◽  
Adult Rat ◽  
Positron Emission ◽  
Ionisation Mass Spectrometry ◽  
Adult Rat Brain ◽  
The Central Nervous System ◽  
First Time

Abstract Background Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended. A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure). N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation. Changes in N-glycosylation can ultimately affect glycoproteins’ functions, which will have an impact on cell machinery. Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies. Methods With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation. In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS. These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI). Results In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%). This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres. Conclusions Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation. These data represent a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases.

scholarly journals 11C- and 18F-Radiotracers for In Vivo Imaging of the Dopamine System: Past, Present and Future

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 108
Author(s):  
Michael R. Kilbourn
Keyword(s):  
Pet Imaging ◽  
In Vivo Imaging ◽  
Dopamine Synthesis ◽  
Dopamine System ◽  
Synaptic Release ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Pet Radiotracers ◽  
Selection Of

The applications of positron emission tomography (PET) imaging to study brain biochemistry, and in particular the aspects of dopamine neurotransmission, have grown significantly over the 40 years since the first successful in vivo imaging studies in humans. In vivo PET imaging of dopaminergic functions of the central nervous system (CNS) including dopamine synthesis, vesicular storage, synaptic release and receptor binding, and reuptake processes, are now routinely used for studies in neurology, psychiatry, drug abuse and addiction, and drug development. Underlying these advances in PET imaging has been the development of the unique radiotracers labeled with positron-emitting radionuclides such as carbon-11 and fluorine-18. This review focuses on a selection of the more accepted and utilized PET radiotracers currently available, with a look at their past, present and future.

Expression of ERG11 and efflux pump genes CDR1, CDR2 and SNQ2 in voriconazole susceptible and resistant Candida glabrata strains

2019 ◽  
Vol 58 (1) ◽  
pp. 30-38
Author(s):  
Patricia Navarro-Rodríguez ◽  
Adela Martin-Vicente ◽  
Loida López-Fernández ◽  
Josep Guarro ◽  
Javier Capilla
Keyword(s):  
Gene Expression ◽  
Candida Glabrata ◽  
Efflux Pump ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Clear Correlation ◽  
Synonymous Mutations ◽  
First Time

AbstractCandida glabrata causes difficult to treat invasive candidiasis due to its antifungal resistance, mainly to azoles. The aim of the present work was to study the role of the genes ERG11, CDR1, CDR2, and SNQ2 on the resistance to voriconazole (VRC) in a set of C. glabrata strains with known in vitro and in vivo susceptibility to this drug. Eighteen clinical isolates of C. glabrata were exposed in vitro to VRC, and the expression of the cited genes was quantified by real time quantitative polymerase chain reaction (q-PCR). In addition, the ERG11 gene was amplified and sequenced to detect possible mutations. Ten synonymous mutations were found in 15 strains, two of them being reported for the first time; however, no amino acid changes were detected. ERG11 and CDR1 were the most expressed genes in all the strains tested, while the expression of CDR2 and SNQ2 was modest. Our results show that gene expression does not directly correlate with the VRC MIC. In addition, the expression profiles of ERG11 and efflux pump genes did not change consistently after exposure to VRC. Although individual analysis did not result in a clear correlation between MIC and gene expression, we did observe an increase in ERG11 and CDR1 expression in resistant strains. It is of interest that considering both in vitro and in vivo results, the slight increase in such gene expression correlates with the observed resistance to VRC.

Neonatal domoic acid alters in vivo binding of [11C]yohimbine to α2-adrenoceptors in adult rat brain

2016 ◽  
Vol 233 (21-22) ◽  
pp. 3779-3785 ◽  
Author(s):  
Majken B. Thomsen ◽  
Thea P. Lillethorup ◽  
Steen Jakobsen ◽  
Erik H. Nielsen ◽  
Mette Simonsen ◽  
...  
Keyword(s):  
Rat Brain ◽  
Domoic Acid ◽  
Α2 Adrenoceptors ◽  
In Vivo Binding ◽  
Adult Rat ◽  
Adult Rat Brain

Advances in Imaging Multiple Sclerosis

2017 ◽  
Vol 37 (05) ◽  
pp. 538-545 ◽  
Author(s):  
Eduardo Caverzasi ◽  
Christian Cordano ◽  
Stephen Hauser ◽  
Roland Henry ◽  
Antje Bischof
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Emission Tomography ◽  
Resonance Imaging ◽  
Ms Imaging ◽  
Positron Emission ◽  
The Central Nervous System ◽  
The Impact

Neuroimaging has emerged as a powerful technology that has enabled visualization of the impact of multiple sclerosis (MS) on the central nervous system in vivo with unprecedented precision. It has played a crucial role in disentangling the chronology of inflammation and neurodegeneration, developing and understanding mechanisms of novel therapeutics, and diagnosing and monitoring the disease in the clinical setting. However, challenges pertaining to the limited resolution, lack of specificity, inherent technological biases, and processing of increasingly big datasets have hindered comprehensive insights into the pathology underlying disability.Here, we review the advances in neuroimaging for MS that have moved the field forward in recent years by addressing the above-mentioned issues, thereby enhancing our knowledge of this yet enigmatic disease. We discuss complementary imaging technologies, including magnetic resonance imaging, positron emission tomography, and optical coherence tomography, the most recent tool in the MS imaging armamentarium that holds promise to act as a surrogate of pathological changes in the central nervous system in a more easily accessible way.

Sign in / Sign up

Export Citation Format

Share Document