Downregulation of spinal angiotensin converting enzyme 2 is involved in neuropathic pain associated with type 2 diabetes mellitus in mice

Yamagata, Ryota; Nemoto, Wataru; Nakagawasai, Osamu; Takahashi, Kohei; Tan-No, Koichi

doi:10.1016/j.bcp.2020.113825

Cited by 34 publications

(31 citation statements)

References 53 publications

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“…In addition, SARS-CoV-2 may reach the cerebral vasculature through the general circulation (Baig et al 2020), breaching the blood-brain barrier and invading and injuring the brain parenchyma. SARS-CoV-2 may bind to its receptor Angiotensin Converting Enzyme 2 (ACE2) expressed in endothelial cells of cerebral capillaries (Peña Silva et al 2012), and within the brain parenchyma in both neurons and microglia (Yamagata et al 2020). Since the blood-brain barrier is disrupted in hypertension (Setiadi et al 2018) and hypertension is a frequent comorbidity for COVID-19, these patients may have a higher risk of cerebral complications.…”

Section: Sars-cov-2 Injures the Brainmentioning

confidence: 99%

COVID-19, Angiotensin Receptor Blockers, and the Brain

Saavedra

2020

Cell Mol Neurobiol

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Section: Sars-cov-2 Injures the Brainmentioning

confidence: 99%

COVID-19, Angiotensin Receptor Blockers, and the Brain

Saavedra

2020

Cell Mol Neurobiol

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“…All this indicates that SARS-CoV2 may have higher neuroinvasive potential compared to previous HCoVs. It was also shown that the SARS-CoV-2 receptor ACE2 is expressed in endothelial cells of cerebral capillaries, and within the brain parenchyma in both neurons and microglia [69]. However, there is no complete expression profile of the catalytic enzymes that are required for CoV entry, such as transmembrane serine protease 2 (TMPRSS2) and Furin, on the surface of the nervous tissue cells, from where the COVID-19 can inter to the human nervous system.…”

Section: Sars-cov-2 Cellular Entry Receptorsmentioning

confidence: 99%

SARS-CoV-2 Infection Reaches the Human Nervous System: How?

Uversky¹,

Elrashdy²,

Aljadawi³

et al. 2020

Preprint

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Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

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“…Neurological symptoms such as disturbance of consciousness, epilepsy and neuralgia may indicate invasion of SARS-CoV-2 into the central nervous system (Wu et al, 2020). Although the expression of ACE2 receptor in the human nervous system has not been fully identified, ACE2 was detected in neuron and microglia in the spinal dorsal horn of mice (Yamagata et al, 2020). Pre-vious studies showed that the ACE/Ang II/AT1 receptor pathway facilitated pain transmission in the spinal dorsal horn, while the ACE2/ Ang (1-7)/Mas receptor pathway might alleviate pain through the inhibition of p38 mitogen-activated protein kinase phosphorylation (Nemoto et al, 2013;Yamagata et al, 2020).…”

mentioning

confidence: 99%

“…Although the expression of ACE2 receptor in the human nervous system has not been fully identified, ACE2 was detected in neuron and microglia in the spinal dorsal horn of mice (Yamagata et al, 2020). Pre-vious studies showed that the ACE/Ang II/AT1 receptor pathway facilitated pain transmission in the spinal dorsal horn, while the ACE2/ Ang (1-7)/Mas receptor pathway might alleviate pain through the inhibition of p38 mitogen-activated protein kinase phosphorylation (Nemoto et al, 2013;Yamagata et al, 2020). We suggest that SARS-CoV-2 might infect the ACE2-positive cells in human spinal dorsal horn; the decrease of functional ACE2 then results in the accumulation of Ang II and the decrease of Ang (1-7); consequently, SARS-CoV-2 infection in the spinal cord could induce pain.…”

mentioning

confidence: 99%

Pain: A potential new label of COVID-19

Cui

Wang

et al. 2020

Brain, Behavior, and Immunity

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Fig. 1. The potential mechanism of pain induced by SARS-CoV-2 in COVID-19.

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Downregulation of spinal angiotensin converting enzyme 2 is involved in neuropathic pain associated with type 2 diabetes mellitus in mice

Cited by 34 publications

References 53 publications

COVID-19, Angiotensin Receptor Blockers, and the Brain

COVID-19, Angiotensin Receptor Blockers, and the Brain

SARS-CoV-2 Infection Reaches the Human Nervous System: How?

Pain: A potential new label of COVID-19

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