Biology subjects

West, C. L.

Publications and source records attributed to West, C. L..

3 recordsLinked to original sources

bioRxiv2024

A lasting impact of serotonergic psychedelics on visual processing and behavior

Serotonergic psychedelics (e.g., psilocybin, LSD) have potential to treat psychiatric disorders, with therapeutic effects lasting days to weeks after a single dose. Prominent theories suggest that psychedelics have a lasting effect on hierarchical brain circuits, reducing top-down influence on information processing to facilitate an unbiased, bottom-up reassessment of the world, but direct and concrete evidence for such an effect is lacking. Here we directly tested this hypothesis in both humans and mice, assessing predictive processing in the fronto-visual system in the days after a single psychedelic exposure. Individuals who recently (<3 weeks) used 5-HT2AReceptor agonist psychedelics (psilocybin, LSD) were assessed via electroencephalography (EEG) and electrooculography recordings during a saccadic prediction task and compared to age- and sex-matched non-users. Compared to non-users, recent psychedelic users produced fewer fast saccades and less suppression of EEG delta/theta power to predictively presented stimuli, pointing to a disruption of predictive processing. These changes correlated with time since psychedelic use and were replicated in a second cohort taking a different serotonergic psychedelic (5-MeO-DMT). Direct recordings of primary visual cortex (V1) in mice administered psilocybin (1 mg/kg) evinced a similar loss of predictive suppression 24-hrs after the dose. This coincided with weakened top-down modulation of V1 from anterior cingulate area (ACa), a subregion of medial prefrontal cortex, along with clear spine growth in ACa neurons that project to V1. These results suggest that psychedelic-induced neural plasticity serves to reorganize feedback circuits in the cortex and relax top-down influence on bottom-up sensory processing - an effect that persists beyond the acute exposure period and may underlie a therapeutic window.

neuroscience↗

bioRxiv2022

A novel biopolymer for mucosal adjuvant against respiratory pathogens

Mucosal vaccinations for respiratory pathogens provide effective protection as they stimulate localized cellular and humoral immunities at the site of infection. Currently, the major limitation of intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a novel biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, using COVID as an example, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC-vaccinated animals were largely resistant to the lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with animal weights and behavior returning to normal 22 days post-infection. In contrast, animals intranasally vaccinated with AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post-infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses.

bioengineering↗

bioRxiv2020

ScRNA-seq reveals tumor microenvironment remodeling induced by local intervention-based immunotherapy

Laser immunotherapy (LIT) combines local photothermal therapy (PTT), to disrupt tumor homeostasis and release tumor antigens, and an intratumorally administered immunostimulant, N-dihydrogalactochitosan (GC), to induce antitumor immune responses. We performed single-cell RNA sequencing on tumor-infiltrating leukocytes of MMTV-PyMT mouse mammary tumors to characterize LIT-induced myeloid and lymphoid compartment remodeling. Analysis of 49,380 single cell transcriptomes from different treatment groups revealed that proinflammatory IFN, IFN{gamma}, and TNF cytokine signaling pathways were enriched in both lymphoid and myeloid cells isolated from LIT-treated tumors. The CD4+ and CD8+ T cells in LIT treated tumors resided in an activated state while immune cells in untreated and PTT-treated tumors remained in a neutral/resting state. Additionally, monocytes recruited into the LIT-treated tumors were driven towards proinflammatory M1-like macrophage phenotypes or monocyte-derived dendritic cells. Our results reveal that LIT prompts immunological remodeling of the tumor microenvironment by initiating broad proinflammatory responses to drive antitumor immunity. STATEMENT OF SIGNIFICANCETranscriptome profiling of tumor infiltrating leukocytes revealed that localized laser immunotherapy (LIT) greatly enhanced antitumor T cell activity by promoting proinflammatory myeloid cell responses within the tumor microenvironment. This manuscript demonstrates that LIT broadly stimulates antitumor immunity and has great potential to synergize with current immunotherapies to increase their efficacy.

cell biology↗