Here is a very interesting article in which the the authors posit that mental fatigue acts as a compensatory 'gating' mechanism, due to the perturbation of higher order CNS constructs there is reduced top-down mediation of sensor input and thus "sensory overload" results , this then leads to down regulating arousal to diminish this perceptive hyperactivity. The top-down modulation, or high order gating, uses excessive resources as it requires constant monitoring and weighting of all senses...This draws obvious parallels to various pathologies; MS, Autism, ADHD, Schizophrenia etc.
https://www.ncbi.nlm...cles/PMC533886/
"Based on this literature and observations from our
own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate
neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis
factor-α, IL-1β and IL-6 could be involved in the pathophysiology of mental fatigue through their
ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the
blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons,
thereby attenuating glutamate transmission..."
"It may be that mental fatigue is a stereotypical reaction to disturbance of "higher" brain functions. The brain, with its billions of specialized neurons and supporting glial cells, works as a "whole" organ. Every disturbance of brain homeostasis, no matter where the anatomical localization is, would therefore attenuate brain capacity for information processing and, as a consequence, information intake. One way to diminish information intake and processing at the cellular level would be to impair glutamate neurotransmission by attenuating the glial support and especially diminishing the astroglial capacity to clear [Glu]ec. The initial consequence would be slightly increased [Glu]ec, with less precision in glutamate transmission. This would disintegrate the "filter", which normally selects information and prevents it from reaching the cerebral cortex. We can take the sound from a low-frequency fan as an example. This sound is normally sorted out after hearing it for a while. If this sound is handled with less precision by auditory recognition systems, it will continually be recognized by brain centers as "new" information and be processed in the cerebral cortex as long as the sound is on. The "filter" that normally restrains already recognized information from reaching higher brain centers, has been "opened". From a physiological point of view, it seems appropriate that the individual, and not the brain at the synaptic level, should determine which information should reach, and be processed by, the cerebral cortex. The decreased attention, increased loudness and light sensitivity, and irritability could be physiological ways of avoiding overstimulation of higher cortical centers. In case the individuals cannot protect themselves from too much sensory stimulation, the filter's opening leads to overstimulation of the cerebral cortex. Here, the final shutdown of the glutamate transmission could be one mechanism underlying mental exhaustion (figure (figure11)."
From theory onto application.
I suspect that for those with systemic inflammation type of ailments upregulating GLT-1 might be a viable target for, at least some symptomatic remission of the otherwise crippling fatigue that accompany them. For me this may be an option to attenuate what I can only assume is hyper glutaminergic tone resulting from many years of Lyme's disease. Interestingly I became aware of the therapeutic potential after having read an article of Ceftriaxone effectively clearing b- Amyloid plaque in small animal models of Alz; this was of further interest given the Ceftriaxone could then offer a 2 birds with one stone type of scenario. No doubt chronic neuroinflammation induces plaque formation, while that in itself is not the end goal for me per se, more-so reducing glutaminergic tone, it certainly can't hurt. Unfortunately after some deep thinking my lifestyle and general life circumstances does provide an ideal base for moving forward with IV antibiotics, as there are a multitude of constraints and considerations nor of which are overly trivial.
Nevertheless, in a cursory review of some literature it seems that there may be alternatives to Ceftriaxone - such as supplemental NAC. NAC certainly has effects on the GLT-1 transporter, although most research has been within the addiction framework, whereby function has been "rescued" following chronic drug administration. Yet, also there seems within the literature and more of recent, disparate and even conflicting findings regarding the potential utility of this as raised in this post: http://www.longecity...oke-prone-rats/.
Of course there are alternatives for addressing this in a more transient fashion, NMDA antagonists could be employed such as DXM, or Metamine. While Metamine of course is purposely marketed for Alzheimer's, it from what I gather, does not actively clear b amyloid but rather reduces its accumulation and thus is more prophylactically administered.
Anyway, sorry for the lack of direction in this post. Honestly, I entertain discussion on both sides of this.
