Brain cells

[Creekside]

It makes me think of electronics and the role of resistors and capacitors in transmitting clear signals.
I have impress of a "gain" on the sensory pathway.

It might help to toss a couple of electronic engineers (signal processing, transmission, circuit layout, fault tracers) into those wine parties. Maybe with enough wine, a comment from a neuroanatomy expert might trigger a comment from a circuit layout expert about a similar effect he noticed in an electronic circuit, and what was eventually found to be responsible.

 

[ScoutB]

When reading this post, I had to think of the Fujimoto et al. 2025 paper that showed the *systematic* increase in AMPA receptors.

Yes that paper is interesting (thread here).

I happened to be reading this article: Progesterone Modulates Neuronal Excitability Bidirectionally the other day, where they argue that progesterone exposure increases AMPA receptors over time in the brain (increasing excitability). This is in contrast to progesterone's *acute* action as a sedative:

[...] progesterone metabolite [allopregnanolone] reduces excitability by enhancing inhibitory neurotransmission mediated by GABA-A receptors.

Progesterone goes up and down during the second half of the menstrual cycle (the luteal phase):


So the researchers speculate this fluctuation could lead to more AMPA receptors (and excitation) at the end of the cycle:

The GABAergic inhibition is strong during the [early] luteal phase when progesterone levels are high. However, the decline in progesterone levels later in the luteal phase diminishes GABAergic inhibition. On the other hand, high progesterone levels during the luteal phase would also activate [progesterone receptors] and enhance AMPA receptor-mediated glutamatergic transmission.

If extra AMPA receptors did contribute to feeling worse (which we don't know), and people have more of them at the end of the menstrual cycle, that could align with the findings of another study:

Examination of the number, presence and severity of long COVID symptoms across the menstrual cycle revealed symptom severity was increased after progesterone withdrawal during the peri-menstrual and proliferative phases.

(The potential bidirectional relationship between long COVID and menstruation)


Of course, even without LC or ME/CFS, the peri-menstrual phase makes a lot of people feel like crap. So symptoms being at their worst then is pretty unsurprising and may not relate to the actual disease mechanism.