The COVID-19 pandemic has been going on for nearly 3 years, but there are many problems still in the clouds.
For example, in addition to attacking the lungs and respiratory tracts, the new coronavirus can also infect many tissues and organs other than the respiratory system, including , the central nervous system, and show corresponding symptoms.
Studies have shown that more than 30% of hospitalized new coronary patients exhibit neurological or neuropsychiatric symptoms, and some patients also have varying degrees of encephalitis .
In addition, the increasingly popular sequelae of infection with the new coronavirus, the so-called long-term coronavirus syndrome, also includes a series of neuropsychiatric symptoms that last for 4 weeks and longer.
However, how does the new coronavirus attack central nervous system ? What is the specific target of the attack? How does infection cause a series of neuropsychiatric symptoms? The answers to these questions are basically guesses and lack of key evidence.
Now, a recent study published by the Brazilian team of scientists in the Proceedings of the American Academy of Sciences (PNAS) has revealed the specific targets of the new coronavirus attacking the human brain with credible evidence, and explained the impact of new coronavirus infection on brain structure, metabolism and function, giving a good answer to the above puzzle.
The new coronavirus mainly attacks the "logistics" cells of the brain
The brain tissue is mainly composed of functional neurons and non-neuronal cells that provide logistical support for neurons.
The latter, the most abundant and mainly astrocytes, not only provides biochemical and nutritional support to brain neurons, regulates the levels of neurotransmitters and other substances that may interfere with neuronal function (such as potassium), but also maintains the integrity of the blood-brain barrier that protects the brain from pathogens and toxins, and helps maintain brain homeostasis. This study by
Brazilian shows that the new coronavirus causes brain infection and triggers neuropsychiatric symptoms through attacks on astrocytes.
researchers used brain tissue collected from 26 patients who died of COVID-19 infection to provide evidence for the infection of astrocytes by immune tissue chemical staining technology.
The so-called immunohistochemical staining technology is to allow specific chemical components in the tissue to display a specific color through the reaction of labeled antigen antibodies.
Brazilian researchers used three immunohistochemical staining techniques. One is to identify the glial fibrous acidic protein (GFAP) characteristic of astrocytes. GFAP+ cells show red fluorescence; the other is to identify the replication of the new coronavirus (dsRNA, which only appears briefly when the virus replicates, indicating that there is viral infection and replication, rather than just the "dead" genetic material) present (magenta; the other is to identify the spike protein of the new coronavirus, which appears green (dsRNA). Color.
When three immunohistochemistry staining images were superimposed, only astrocytes showed all three colors at the same time, indicating that the new coronavirus infected the astrocytes and copied them.
The new coronavirus attack on astrocytes requires NRP1
is known, and the new coronavirus attack infected the lungs and most other tissues. The cells are achieved by binding to the ACE2 receptor on the cell membrane by the viral spike protein; in addition, the two receptors of NRP1 and BSG are also potential infection binding targets for the spike protein .
Researchers have detected brain tissue samples of patients infected with the new coronavirus and showed that astrocytes do not express ACE2 receptors, and can detect a certain level of NRP1 and BSG mRNA, indicating that astrocytes can To express these two receptors. How to determine whether the virus infection depends on the NRP1 (neurocilin-1) receptor?
researchers used neutralizing anti-NRP1 antibodies to pre-cultivate the cells. The neutralization of NRP1 inhibited the infection of the cultured astrocytes by the new coronavirus, confirming that the new coronavirus infected human astrocytes through the NRP1 receptor.
Effect of COVID-19 infection on metabolism and function
Researchers tested the proteomics and metabolomics changes in astrocytes infected with COVID-19.
Results: Compared with the control group, 170 protein expressions in the astrocytes infected with the new coronavirus were changed, of which 68 were up-regulated and 102 were down-regulated. Analysis shows that changes in expression of these proteins have a wide impact on metabolism and function. Among them, the effect on glucose metabolism is the most significant.
Specifically, the changes in protein expression of astrocytes infected by the new coronavirus mainly affect glycolysis / gluconeogenesis , carbon metabolism and pentose phosphate pathway .
Overall, the results showed that oxidative metabolism increased in the astrocytes infected by the novel coronavirus, and the levels of neurons supported by these cells showed a decrease.
In addition, the changes in mitochondria function in infected astrocytes also affect the neurotransmitter levels in the brain.
We know that brain neurotransmitters include glutamate and glutamine excitotransmitters, and inhibitory neurotransmitters mainly composed of γ-aminobutyric acid (GABA).
study shows that while the new coronavirus infection accelerates the metabolism of glucose in astrocytes, it also consumes the excitatory neurotransmitter glutamine. This makes infected people more likely to experience neuroinhibiting symptoms such as fatigue and depression.
Coronavirus infection of astrocytes reduces neuronal vitality
As mentioned above, astrocytes are logistical cells that support brain neurons and are crucial for brain homeostasis. The infection of the new coronavirus on astrocytes may have an indirect effect on neurons.
This study in Brazil shows that, as expected, the novel coronavirus-infected astrocytes can release a soluble factor, which reduces the vitality of the supported neurons.
It can be seen from the above that although the new coronavirus cannot directly infect brain neurons, it can have a significant impact on brain metabolism and function by astrocytes.
cognitive impairment and neuropsychiatric symptoms related to changes in cerebral cortex thickness
In a high-resolution brain magnetic resonance imaging (MRI) scan study, including 81 recovered from mild COVID-19 infection, one-third of the participants complained about the persistence of neuropsychiatric symptoms for 60 days. These symptoms mainly include headache (40%), fatigue (40%), memory changes (30%), anxiety (28%), loss of smell (28%), depression (20%), daytime lethargy (25%), loss of taste (16%) and low sexual desire (14%), etc.
Compared with 81 healthy controls, the COVID-19 infection group experienced higher levels of anxiety and depression, fatigue and excessive daytime sleepiness. Analysis of cerebral cortex thickness by
showed that the orbitofrontal area of the left hemisphere of the brain showed a decrease in cortical thickness, and no increase in cortical thickness was observed in any area.
neuropsychology evaluations of people infected with COVID-19, including episodic verbal memory, continuous attention and alternating attention, and cognitive flexibility, showed that cortical thickness atrophy was associated with neuropsychiatric symptoms and cognitive impairment.
In short, studies from Brazil show that:
- new coronavirus can directly attack brain tissue, and the specific target of attack is astrocytes responsible for maintaining the structure and function of brain neurons;
- infection has a significant impact on the expression and metabolism of astrocyte functional proteins, thus affecting the structure and function of the brain;
- high-resolution magnetic resonance scans show that infection causes a reduction in the cortical thickness of the orbitofrontal area of the brain related to cognitive function, thus providing a good explanation for the long-term existence of neural and neuropsychiatric symptoms of long-term COVID-19 syndrome.
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