Tag: neurogenesis

Role of neuroinflammation mediated potential alterations in adult neurogenesis as a factor for neuropsychiatric symptoms in Post-Acute COVID-19 syndrome-A narrative review

Abstract:

Persistence of symptoms beyond the initial 3 to 4 weeks after infection is defined as post-acute COVID-19 syndrome (PACS). A wide range of neuropsychiatric symptoms like anxiety, depression, post-traumatic stress disorder, sleep disorders and cognitive disturbances have been observed in PACS. The review was conducted based on PRISMA-S guidelines for literature search strategy for systematic reviews.

A cytokine storm in COVID-19 may cause a breach in the blood brain barrier leading to cytokine and SARS-CoV-2 entry into the brain. This triggers an immune response in the brain by activating microglia, astrocytes, and other immune cells leading to neuroinflammation. Various inflammatory biomarkers like inflammatory cytokines, chemokines, acute phase proteins and adhesion molecules have been implicated in psychiatric disorders and play a major role in the precipitation of neuropsychiatric symptoms. Impaired adult neurogenesis has been linked with a variety of disorders like depression, anxiety, cognitive decline, and dementia.

Persistence of neuroinflammation was observed in COVID-19 survivors 3 months after recovery. Chronic neuroinflammation alters adult neurogenesis with pro-inflammatory cytokines supressing anti-inflammatory cytokines and chemokines favouring adult neurogenesis. Based on the prevalence of neuropsychiatric symptoms/disorders in PACS, there is more possibility for a potential impairment in adult neurogenesis in COVID-19 survivors. This narrative review aims to discuss the various neuroinflammatory processes during PACS and its effect on adult neurogenesis.

Source: Saikarthik J, Saraswathi I, Alarifi A, Al-Atram AA, Mickeymaray S, Paramasivam A, Shaikh S, Jeraud M, Alothaim AS. Role of neuroinflammation mediated potential alterations in adult neurogenesis as a factor for neuropsychiatric symptoms in Post-Acute COVID-19 syndrome-A narrative review. PeerJ. 2022 Nov 4;10:e14227. doi: 10.7717/peerj.14227. PMID: 36353605; PMCID: PMC9639419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639419/ (Full text)

Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms

Abstract:

Coronavirus disease 2019 (COVID-19), represents an enormous new threat to our healthcare system and particularly to the health of older adults. Although the respiratory symptoms of COVID-19 are well recognized, the neurological manifestations, and their underlying cellular and molecular mechanisms, have not been extensively studied yet. Our study is the first one to test the direct effect of serum from hospitalised COVID-19 patients on human hippocampal neurogenesis using a unique in vitro experimental assay with human hippocampal progenitor cells (HPC0A07/03 C). We identify the different molecular pathways activated by serum from COVID-19 patients with and without neurological symptoms (i.e., delirium), and their effects on neuronal proliferation, neurogenesis, and apoptosis.

We collected serum sample twice, at time of hospital admission and approximately 5 days after hospitalization. We found that treatment with serum samples from COVID-19 patients with delirium (n = 18) decreased cell proliferation and neurogenesis, and increases apoptosis, when compared with serum samples of sex- and age-matched COVID-19 patients without delirium (n = 18). This effect was due to a higher concentration of interleukin 6 (IL6) in serum samples of patients with delirium (mean ± SD: 229.9 ± 79.1 pg/ml, vs. 32.5 ± 9.5 pg/ml in patients without delirium).

Indeed, treatment of cells with an antibody against IL6 prevented the decreased cell proliferation and neurogenesis and the increased apoptosis. Moreover, increased concentration of IL6 in serum samples from delirium patients stimulated the hippocampal cells to produce IL12 and IL13, and treatment with an antibody against IL12 or IL13 also prevented the decreased cell proliferation and neurogenesis, and the increased apoptosis. Interestingly, treatment with the compounds commonly administered to acute COVID-19 patients (the Janus kinase inhibitors, baricitinib, ruxolitinib and tofacitinib) were able to restore normal cell viability, proliferation and neurogenesis by targeting the effects of IL12 and IL13.

Overall, our results show that serum from COVID-19 patients with delirium can negatively affect hippocampal-dependent neurogenic processes, and that this effect is mediated by IL6-induced production of the downstream inflammatory cytokines IL12 and IL13, which are ultimately responsible for the detrimental cellular outcomes.

Source: Borsini, A., Merrick, B., Edgeworth, J. et al. Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01741-1  (Full text)

Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells

Abstract:

Neuroimaging evidence showed structural and/or functional abnormalities existing in the central nervous system, especially the hippocampus, in chronic fatigue syndrome (CFS) patients. However, its pathophysiologic mechanisms are unclear in part due to the lack of an applicable animal model. We established a chronic fatigue murine model by six repeated injections of Brucella abortus antigen to mice, which was manifested as reduced daily running activity and hippocampal atrophy. Thereafter, resveratrol, a polyphenolic activator of sirtuin 1, was used for treatment in this model. Daily running activity was increased by more than 20%, and the hippocampus was enlarged after 4-week resveratrol therapy.

Furthermore, resveratrol inhibited neuronal apoptosis and expression of hippocampal acetylated p53 in the fatigue mice. Resveratrol also improved neurogenesis and expression of brain-derived neurotrophic factor mRNA in the hippocampus. We concluded that repeated injection of B. abortus antigen could induce hypoactivity and hippocampal atrophy in mice. Resveratrol may be effective for improving fatigue symptoms and enlarging the atrophic hippocampus by repressing apoptosis and promoting neurogenesis.

 

Source: Moriya J, Chen R, Yamakawa J, Sasaki K, Ishigaki Y, Takahashi T. Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells. Biol Pharm Bull. 2011;34(3):354-9. https://www.jstage.jst.go.jp/article/bpb/34/3/34_3_354/_article (Full article)