The anti-inflammatory effects of photobiomodulation are mediated by cytokines: Evidence from a mouse model of inflammation

There is an urgent need for therapeutic approaches that can prevent or limit neuroinflammatory processes and prevent neuronal degeneration. Photobiomodulation (PBM), the therapeutic use of specific wavelengths of light, is a safe approach shown to have anti-inflammatory effects. The current study was aimed at evaluating the effects of PBM on LPS-induced peripheral and central inflammation in mice to assess its potential as an anti-inflammatory treatment. Daily, 30-min treatment of mice with red/NIR light (RL) or RL with a 40 Hz gamma frequency flicker for 10 days prior to LPS challenge showed anti-inflammatory effects in the brain and systemically. PBM downregulated LPS induction of key proinflammatory cytokines associated with inflammasome activation, IL-1β and IL-18, and upregulated the anti-inflammatory cytokine, IL-10. RL provided robust anti-inflammatory effects, and the addition of gamma flicker potentiated these effects. Overall, these results demonstrate the potential of PBM as an anti-inflammatory treatment that acts through cytokine expression modulation

Social behavior and influence of the immune system in a mouse model of autism

Ph.D. University of Hawaii at Manoa 2013.Includes bibliographical references.Autism is a common neurodevelopmental disorder with an unknown cause or cure. Impairments in social behavior constitute a diagnostic symptom of autism along with communication deficits and repetitive behaviors. There are no biomarkers for autism, meaning that there are no indicators in blood tests, lumbar punctures or body scans that can assist in diagnosis of the disorder. Factors contributing to the emergence of autistic behaviors have been identified; however, effective treatment strategies remain elusive. Therefore, diverse research approaches are necessary to reveal mechanisms underlying this highly prevalent disorder. Mouse models, while unable to replicate human conditions, provide distinct advantages in testing causal hypotheses of disorders. Ideal mouse models for autism display social impairments, communication deficits and repetitive behaviors; however, designing tasks to measure such behaviors presents a unique challenge. A major strength of this laboratory has been in identifying and characterizing behavioral phenomena in rodents. Using knowledge of the natural environment and behavior of the mouse, this laboratory established and adapted several tests to measure behaviors relevant to autism. From these tests, this laboratory and others have found that the BTBR T+tf/J (BTBR) mouse strain displays behaviors that are consistent with those observed in autism. This dissertation demonstrates that BTBR mice show social avoidance, as well as a pattern of behavior analogous to gaze aversion observed in autism, when in closely confined conditions. BTBR mice also display a normal-to-low anxiety profile, suggesting that anxiety is not a primary contributing factor in the social deficits of this strain. In addition, this dissertation shows that immune activation in pregnant mousedams from a high sociability strain produces autism-relevant behavioral deficits in offspring. Finally, the dissertation shows that the placental gene expression of an immune pathway is altered in BTBR mice, which is suggestive of impaired prenatal regulation of immune signaling in this mouse model of autism

Upregulating Human Cathelicidin Antimicrobial Peptide LL-37 Expression May Prevent Severe COVID-19 Inflammatory Responses and Reduce Microthrombosis

COVID-19 is characterized by hyperactivation by inflammatory cytokines and recruitment of macrophages, neutrophils, and other immune cells, all hallmarks of a strong inflammatory response that can lead to severe complications and multi-organ damage. Mortality in COVID-19 patients is associated with a high prevalence of neutrophil extracellular trap (NET) formation and microthrombosis that are exacerbated by hyperglycemia, diabetes, and old age. SARS-CoV-2 infection in humans and non-human primates have revealed long-term neurological consequences of COVID-19, possibly concomitant with the formation of Lewy bodies in the brain and invasion of the nervous system via the olfactory bulb. In this paper, we review the relevance of the human cathelicidin LL-37 in SARS-CoV-2 infections. LL-37 is an immunomodulatory, host defense peptide with direct anti-SARS-CoV-2 activity, and pleiotropic effects on the inflammatory response, neovascularization, Lewy body formation, and pancreatic islet cell function. The bioactive form of vitamin D and a number of other compounds induce LL-37 expression and one might predict its upregulation, could reduce the prevalence of severe COVID-19. We hypothesize upregulation of LL-37 will act therapeutically, facilitating efficient NET clearance by macrophages, speeding endothelial repair after inflammatory tissue damage, preventing α-synuclein aggregation, and supporting blood-glucose level stabilization by facilitating insulin release and islet β-cell neogenesis. In addition, it has been postulated that LL-37 can directly bind the S1 domain of SARS-CoV-2, mask angiotensin converting enzyme 2 (ACE2) receptors, and limit SARS-CoV-2 infection. Purposeful upregulation of LL-37 could also serve as a preventative and therapeutic strategy for SARS-CoV-2 infections

LRRK2 modifies α-syn pathology and spread in mouse models and human neurons

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