Topography and distribution of adenosine A2A and dopamine D2 receptors in the human Subthalamic Nucleus

Emmi, Aron; Antonini, Angelo; Sandre, Michele; Baldo, Andrea; Contran, Martina; Macchi, Verónica; Guidolin, Diego; Porzionato, Andrea; De, Raffaele

doi:10.3389/fnins.2022.945574

Cited by 11 publications

(15 citation statements)

References 54 publications

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“…Immunoperoxidase staining was performed manually according to previously established protocols − following antigen retrieval performed on de-paraffinized tissue sections using Dako EnVision PTLink station according to the manufacturer’s recommendations. Antibodies for ACE2 receptor protein (Rabbit anti-Human polyclonal, citrate buffer HIER, dilution 1:2000, Abcam, code number: ab15348) and TMPRSS2 protein (Rabbit anti-Human monoclonal, citrate buffer HIER, dilution 1:2500, Abcam, code number: ab242384) were employed.…”

Section: Methodsmentioning

confidence: 99%

ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection

Emmi,

Tushevski,

Sinigaglia

et al. 2023

ACS Chem. Neurosci.

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Angiotensin-converting enzyme 2 receptor (ACE2R) is a transmembrane protein expressed in various tissues throughout the body that plays a key role in the regulation of blood pressure. Recently, ACE2R has gained significant attention due to its involvement in the pathogenesis of COVID-19, the disease caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). While ACE2 receptors serve as entry points for the novel coronavirus, Transmembrane Serine Protease 2 (TMPRSS2), an enzyme located on the cell membrane, is required for SARS-CoV-2 S protein priming. Even though numerous studies have assessed the effects of COVID-19 on the brain, very little information is available concerning the distribution of ACE2R and TMPRSS2 in the human brain, with particular regard to their topographical expression in the brainstem. In this study, we investigated the expression of ACE2R and TMPRSS2 in the brainstem of 18 adult subjects who died due to pneumonia/respiratory insufficiency. Our findings indicate that ACE2R and TMPRSS2 are expressed in neuronal and glial cells of the brainstem, particularly at the level of the vagal nuclei of the medulla and the midbrain tegmentum, thus confirming the expression and anatomical localization of these proteins within specific human brainstem nuclei. Furthermore, our findings help to define anatomically susceptible regions to SARS-CoV-2 infection in the brainstem, advancing knowledge on the neuropathological underpinnings of neurological manifestations in COVID-19.

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Section: Methodsmentioning

confidence: 99%

ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection

Emmi,

Tushevski,

Sinigaglia

et al. 2023

ACS Chem. Neurosci.

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“…Images were acquired at a 16-bit intensity resolution over 2048 × 2048 pixels. Z-stacks images were converted into digital maximum intensity z-projections, processed, and analyzed using ImageJ software, as previously reported [46][47][48] .…”

Section: Immunofluorescent Staining and Confocal Microscopymentioning

confidence: 99%

Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei

Emmi

Rizzo

Barzon

et al. 2023

npj Parkinsons Dis.

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Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it is still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms. Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia/respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in the dorsal medulla and in the substantia nigra of five COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2 and characterize the role of brainstem inflammation in COVID-19, its potential implications for neurodegeneration, especially in Parkinson’s disease, require further investigations.

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“…Semi-automatic immunoreactivity quantification (Alpha-Gal Epitopes) was calculated on an average of three ×20 magnification photomicrographs/section as previously established [ 48 , 49 ].…”

Section: Methodsmentioning

confidence: 99%

Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts

Stocco

Barbon

Mammana

et al. 2023

Cells

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Tracheal reconstruction represents a challenge when primary anastomosis is not feasible. Within this scenario, the study aim was to develop a new pig-derived decellularized trachea (DecellT) to be compared with the cryopreserved counterpart (CryoT) for a close predictive analysis. Tracheal segments underwent decellularization by a physical + enzymatic + chemical method (12 cycles); in parallel, cryopreserved samples were also prepared. Once decellularized (histology/DNA quantification), the two groups were characterized for Alpha-Gal epitopes/structural proteins (immunohistochemistry/histology/biochemical assays/second harmonic generation microscopy)/ultrastructure (Scanning Electron Microscopy (SEM))/mechanical behaviour. Cytotoxicity absence was assessed in vitro (extract-test assay/direct seeding, HM1SV40 cell line) while biocompatibility was verified in BALB/c mice, followed by histological/immunohistochemical analyses and SEM (14 days). Decellularization effectively removed Alpha-Gal epitopes; cartilage histoarchitecture was retained in both groups, showing chondrocytes only in the CryoT. Cryopreservation maintained few respiratory epithelium sparse cilia, not detectable in DecellT. Focusing on ECM, preserved structural/ultrastructural organization and collagen content were observed in the cartilage of both; conversely, the GAGs were significantly reduced in DecellT, as confirmed by mechanical study results. No cytotoxicity was highlighted by CryoT/DecellT in vitro, as they were also corroborated by a biocompatibility assay. Despite some limitations (cells presence/GAGs reduction), CryoT/DecellT are both appealing options, which warrant further investigation in comparative in vivo studies.

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Topography and distribution of adenosine A2A and dopamine D2 receptors in the human Subthalamic Nucleus

Cited by 11 publications

References 54 publications

ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection

ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection

Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei

Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts

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