Entry points of SARS-CoV-2 to the brain may be Neurons in the nose & hypothalamus
Researchers have actually zeroed in on the path in which the SARS-CoV-2 virus enters the brain in humans. According to a new study, neurons found in the nose that help us sense smell as well as the hypothalamus – the small region located at the base of the brain, can be the virus’ entry point to the brain.
This research might offer new understandings to deal with COVID-19 patients and also manage the pandemic.
It was shown that specialized glial cell called tanycytes in the hypothalamus, as well as olfactory neurons, could provide an opening for SARS-CoV-2 into the brain, by Dr. Vincent Prevot, formerly a principal investigator supported by the Indo-French Centre for the Promotion of Advanced Research Study (CEFIPRA), supported by the Dept of Science & Technology, Govt. of India in addition to a team of Indian and French researchers. Additionally, they have revealed that, along with the physical effects of viral infection, hypothalamic circuits can function as a center for the countless risk factors. The outcomes of the study are published in the journal ‘bioRxiv’.
Many of the reported signs of COVID-19 could also have a neurological origin, even though it has been considered as a respiratory disease. But, the majority of examinations up until now have not found the virus in the brain, or have discovered it only in the blood vessels or cerebrospinal fluid.
Likewise, ACE2 or angiotensin-converting enzyme 2, a molecule that regulates blood pressure is the only molecule that is used by the coronavirus to bind onto the host cell. Apart from the capillary walls, high levels of ACE2 is not present in the brain.
A curious coincidence struck the scientists – the hypothalamus coordinated or transmitted a lot of the functions affected in severe COVID-19 patients like temperature control, cardiorespiratory function, the senses of odor and taste, and hydration. Additionally, hypothalamic cell networks are involved in most of the threat factors for severe COVID-19, including old age, male sex, metabolic diseases such as diabetes, high blood pressure, or obesity.
The team could discover numerous findings with the support from the European Research Council Synergy grant. It was discovered by Dr. Sreekala Nampoothiri, bioinformatician and postdoctoral fellow, that both the hypothalamus and related regions involved in cardiorespiratory function, smell, or taste expressed the most commonly used protease, transmembrane proteinase, serine 2 (TMPRSS2), and the viral receptor ACE2.
As ACE2- or TMPRSS2-correlated genes play essential functions in the perception of smell, taste, or the hypothalamic regulation of numerous bodily functions, the hypothalamus, and connected regions can thus certainly be infected by the SARS-CoV-2.
ACE2, albeit at reduced levels, and TMPRSS2 was present in tanycytes in a part of the hypothalamus bordered by fenestrated blood vessels, according to Florent Sauve, a French Ph.D. student and other members of the lab. Similarly, ACE2 and TMPRSS2 are expressed in other cells – sensory neurons of the nose, and their fibers entering in the olfactory bulbs of the brain. Therefore, could enter other brain regions – the hypothalamus with its other vital functions, bypassing from neuron to neuron along the olfactory paths as well as the virus could directly impact the sense of smell by infecting these neurons.
An association between the vulnerability of the hypothalamus to infection and the known risk factors for severe COVID-19, such as sex or metabolic diseases was also revealed by the team. The study group wishes that the outcomes of the study will certainly help future researches to expose precisely what cellular, as well as molecular pathways, are activated by a viral infection and whether they can be targeted to improve the result of severe COVID-19 infected individuals.
Entry points of SARS-CoV-2 to the brain may be Neurons in the nose & hypothalamus
Author: Sruthi S
