The Role of Lactylation in Mental Illness: Emphasis on Microglia

Sfera, Adonis; Klein, Carolina A; Anton, Johnathan J.; Kozlakidis, Zisis; Andronescu, Christina V.

doi:10.3390/neuroglia4020009

Cited by 3 publications

(2 citation statements)

References 254 publications

(304 reference statements)

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“…Moreover, HIF-1α also protects enteric neurons as hypoxia caused by IEC oxygen consumption exhibits neuroprotective properties [122]. In another article, we have discussed HIF-1α lactylation and dysfunction in PTSD pathogenesis so we will not dwell on this topic here [123].…”

Section: Ahr and Cellular Senescencementioning

confidence: 99%

Of Soldiers and Their Ghosts: Are We Ready for a Review of PTSD Evidence?

Sfera,

Anton,

Imran

et al. 2023

BioMed

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Psychosocial trauma has accompanied mankind since time immemorial and has been sufficiently portrayed in art and literature to suggest that posttraumatic stress disorder may be as old as combat itself. Since war is more frequent in human history than peace, public health measures are confined to mitigating the detrimental impact of battlefield experiences on combat participants. At present, PTSD outcome studies show mixed results, marked by high nonresponse rates, therapy dropout, and completed suicide, suggesting that novel strategies are urgently needed. Those of us who work routinely with combat veterans have noted an increasing trend of patients preferring mindfulness-based therapies as opposed to trauma-centered treatments, such as prolonged exposure or trauma-focused cognitive behavioral therapy. Preference for mindfulness over trauma-based therapies appears to coincide with the shift in research focus from the amygdala and fear to the insular cortex and interoceptive awareness. Therefore, rethinking PTSD as insular pathology is driven by the recent findings that neurons in this cortical area not only regulate cardiac rhythm but also record past intestinal inflammations. These discoveries likely explain the high comorbidity of stress-related disorders with premature endothelial senescence and a dysfunctional intestinal barrier. Moreover, the identification of the cholinergic anti-inflammatory pathway and the revelation that endothelial cells express alpha-7 nicotinic receptors has brought PTSD prevention and early detection within reach. In this narrative review, we discuss the relationship between early vascular aging, gut barrier disruption, and PTSD. We also examine the link between this pathology and faulty interoceptive awareness, surmising that hypertension and decreased heart rate variability are PTSD risk factors, while lipopolysaccharide, lipopolysaccharide binding protein, soluble CD14, microbial cell-free DNA, acyloxyacyl hydrolase, and IL22 comprise early detection markers of this disorder.

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Section: Ahr and Cellular Senescencementioning

confidence: 99%

Of Soldiers and Their Ghosts: Are We Ready for a Review of PTSD Evidence?

Sfera,

Anton,

Imran

et al. 2023

BioMed

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“…Finally, we discuss new therapies, including transcutaneous vagal stimulation, aryl hydrocarbon receptor ligands, and recombinant IL22-mediated gut barrier rehabilitation. Less emphasis will be placed on the SCZ topics discussed in other articles, such as premature cellular senescence, ferroptosis, DNA methylation, innate lymphoid cells (ILCs), and lactylation [82,83].…”

mentioning

confidence: 99%

Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?

Sfera

2023

Reports

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In 1957, Arvid Carlsson discovered that dopamine, at the time believed to be nothing more than a norepinephrine precursor, was a brain neurotransmitter in and of itself. By 1963, postsynaptic dopamine blockade had become the cornerstone of psychiatric treatment as it appeared to have deciphered the “chlorpromazine enigma”, a 1950s term, denoting the action mechanism of antipsychotic drugs. The same year, Carlsson and Lindqvist launched the dopamine hypothesis of schizophrenia, ushering in the era of psychopharmacology. At present, six decades later, although watered down by three consecutive revisions, the dopamine model remains in vogue. The latest emendation of this paradigm proposes that “environmental and genetic factors” converge on the dopaminergic pathways, upregulating postsynaptic transmission. Aryl hydrocarbon receptors, expressed by the gut and blood–brain barrier, respond to a variety of endogenous and exogenous ligands, including dopamine, probably participating in interoceptive awareness, a feed-back loop, conveying intestinal barrier status to the insular cortex. The conceptualization of aryl hydrocarbon receptor as a bridge, connecting vagal terminals with the microbiome, may elucidate the aspects of schizophrenia seemingly incongruous with the dopamine hypothesis, such as increased prevalence in urban areas, distance from the equator, autoantibodies, or comorbidity with inflammatory bowel disease and human immunodeficiency 1 virus. In this review article, after a short discussion of schizophrenia outcome studies and insight, we take a closer look at the action mechanism of antipsychotic drugs, attempting to answer the question: do these agents exert their beneficial effects via both dopaminergic and nondopaminergic mechanisms? Finally, we discuss potential new therapies, including transcutaneous vagal stimulation, aryl hydrocarbon receptor ligands, and restoring the homeostasis of the gut barrier.

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Association of histone modification with the development of schizophrenia

Chen,

Zhu,

et al. 2024

Biomedicine & Pharmacotherapy

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The Role of Lactylation in Mental Illness: Emphasis on Microglia

Cited by 3 publications

References 254 publications

Of Soldiers and Their Ghosts: Are We Ready for a Review of PTSD Evidence?

Of Soldiers and Their Ghosts: Are We Ready for a Review of PTSD Evidence?

Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?

Association of histone modification with the development of schizophrenia

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