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Angry Redhead @sidherian.bsky.social · 10h

This creates a plausible pathway for motor neuron degeneration, though causality is not yet proven.
We need long-term studies tracking SARS-CoV-2 survivors, neurodegeneration markers, and MND incidence.
The virus’s neurological reach may be wider than we realise.”

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Angry Redhead @sidherian.bsky.social · 10h

Bottom line:
SARS-CoV-2 delivers multiple hits to motor neurons: infection, inflammation, vascular compromise, protein aggregation.

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Angry Redhead @sidherian.bsky.social · 10h

Multiple hits = cumulative vulnerability. This shows how environmental exposures, lifestyle factors, & viral infections can converge on the same neurodegenerative pathways. SARS-CoV-2 may not create MND from scratch, but it could push already vulnerable neurons over the edge.

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Angry Redhead @sidherian.bsky.social · 10h

including motor neuron disease (MND).
Chronic neuronal stress and inflammation can prime cells for degeneration. Conceptually, prior neuronal injury (e.g. from TBI) could lower the threshold for SARS-CoV-2–induced neuronal damage increasing MND risk or hastening its onset.

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Angry Redhead @sidherian.bsky.social · 10h

Systemic immune activation can lead to autoimmune or bystander neuronal injury.
In genetically susceptible people, this could trigger or worsen MND.
Traumatic brain injury (TBI), including repeated concussions from sports like rugby, is a known risk factor for neurodegenerative diseases

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Angry Redhead @sidherian.bsky.social · 10h

Vascular and metabolic stress:
SARS-CoV-2 can cause microthrombi, hypoxia and endothelial dysfunction. Motor neurons are highly metabolically active, so even mild oxygen or nutrient deficits can accelerate degeneration.
Immune-mediated damage:

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Angry Redhead @sidherian.bsky.social · 10h

which can promote TDP-43 aggregation, a hallmark of ALS, leading to neuron dysfunction & death.

ER is responsible for folding & processing proteins properly.

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Angry Redhead @sidherian.bsky.social · 10h

Neuroinflammation:
Infected neurons trigger microglial activation & astrocyte dysfunction, creating chronic inflammation.
Neuroinflammation is a known driver of MND, especially ALS.
Protein misfolding:
Viral infection causes ER (Endoplasmic Reticulum) stress and oxidative stress,

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Angry Redhead @sidherian.bsky.social · 10h

Let’s break down the neuropathology.
Direct infection of motor neurons:
SARS-CoV-2 enters via ACE2, NRP1, CD147 receptors and can replicate inside neurons.
These long, metabolically demanding cells are highly vulnerable to injury.

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Angry Redhead @sidherian.bsky.social · 10h

Via @jamesthrot (pseudonym) Consultant Neuropathologist UK

“Since I’m a neuropathologist, I’ll put my two cents into this MND discussion.

SARS-CoV-2 isn’t just a respiratory virus. Emerging evidence shows it can infect human motor neurons. Could this link to motor neuron disease (MND)?

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Angry Redhead @sidherian.bsky.social · 2d

Source:
Yokohama City University
Journal reference:
Fujimoto, Y., et al. (2025). Systemic increase of AMPA receptors associated with cognitive impairment of long COVID. Brain Communications. doi.org/10.1093/braincomms/fcaf337

www.news-medical.net/news/2025093...

Systemic increase of AMPA receptors associated with cognitive impairment of long COVID

Fujimoto et al. report that the patients with cognitive impairments after SARS-CoV-2 infection showed significant AMPA receptors upregulation across their

doi.org

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Angry Redhead @sidherian.bsky.social · 2d

In summary, the team's findings resolve key uncertainties about the biological basis of Long COVID brain fog and may pave the way for novel diagnostic tools and effective therapies for patients suffering from this condition.”

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Angry Redhead @sidherian.bsky.social · 2d

This could encourage the healthcare industry to accelerate the development of diagnostic and therapeutic approaches for this disorder," concludes Prof. Takahashi.

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Angry Redhead @sidherian.bsky.social · 2d

While further efforts will be needed to find a definitive solution for Long COVID, this work is a promising step in the right direction. "Our findings clearly demonstrate that Long COVID brain fog should be recognized as a legitimate clinical condition.

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Angry Redhead @sidherian.bsky.social · 2d

"By applying our newly developed AMPA receptor PET imaging technology, we aim to provide a novel perspective and innovative solutions to the pressing medical challenge that is Long COVID," remarks Prof. Takahashi.

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Angry Redhead @sidherian.bsky.social · 2d

For example, drugs that suppress AMPAR activity could be a viable approach to mitigate brain fog. Interestingly, the team's analysis also demonstrated that imaging data can be used to distinguish patients from healthy controls with 100% sensitivity and 91% specificity.

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Angry Redhead @sidherian.bsky.social · 2d

Taken together, the study's findings represent a crucial step forward in addressing many unresolved issues regarding Long COVID. The systemic increase in AMPARs provides a direct biological explanation for the cognitive symptoms, highlighting a target for potential treatments.

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Angry Redhead @sidherian.bsky.social · 2d

By comparing imaging data from 30 patients with Long COVID to 80 healthy individuals, the researchers found a notable and widespread increase in the density of AMPARs across the brains of patients.

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Angry Redhead @sidherian.bsky.social · 2d

and learning-based on prior research into psychiatric and neurological disorders such as depression, bipolar disorder, schizophrenia, and dementia. Thus, they used a novel method called [11C]K-2 AMPAR PET imaging to directly visualize and quantify the density of AMPARs in the living human brain.

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Angry Redhead @sidherian.bsky.social · 2d

As explained in their paper, published in Brain Communications on October 01, 2025, the team hypothesized that patients with brain fog might exhibit disrupted expression of AMPA receptors (AMPARs)-key molecules for memory

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Angry Redhead @sidherian.bsky.social · 2d

To address this challenge, a research team led by Professor Takuya Takahashi from the Graduate School of Medicine at Yokohama City University, Japan, has made a significant breakthrough in understanding the cause of Long COVID brain fog.

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Angry Redhead @sidherian.bsky.social · 2d

Since it's difficult to observe the molecules that govern communication between brain cells directly, researchers are left without objective biomarkers to confirm a Long COVID diagnosis or develop therapies.

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Angry Redhead @sidherian.bsky.social · 2d

Unfortunately, despite its prevalence, the underlying causes of Long COVID and brain fog remain poorly understood. Previous imaging studies have shown some structural changes in the brain, but they could not pinpoint the molecular dysfunctions responsible for the cognitive symptoms.

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Angry Redhead @sidherian.bsky.social · 2d

Given the hundreds of millions of global cases, Long COVID represents a massive public health and socioeconomic challenge, as it severely impacts people's ability to work and perform daily activities.

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Angry Redhead @sidherian.bsky.social · 2d

Among the most common and debilitating of these is cognitive impairment, often referred to as "brain fog," which affects over 80% of people with Long COVID.

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