Biology subjects

Ferris, C.

Publications and source records attributed to Ferris, C..

5 recordsLinked to original sources

bioRxiv2025

Dynamic interaction between stress hormones and neutrophils promotes neutrophil extracellular trap formation with behavioral consequences

Recent studies have highlighted the crosstalk between neuroendocrine responses and the immune system but the mechanisms underlying this cooperation are still not well understood. The stress response is associated with peripheral inflammation suggesting that stress hormones including glucocorticoids and catecholamines could modulate the function of innate immune cells like neutrophils. Likewise, inflammatory mediators produced by immune cells are known to contribute to psychiatric diseases like major depressive disorder. Here we investigated the dynamic relationship between stress hormones and neutrophils and their contribution to mood disorders. We found that chronic restraint stress leads to plasma elevation of neutrophil extracellular traps (NETs) and increased NET formation in mice. Interestingly, the stress hormones, cortisol and epinephrine induce NET formation in human neutrophils ex vivo. Activation of neutrophils to form NETs leads to their increased expression of adrenergic and glucocorticoid receptors and neutrophil production of both cortisol and epinephrine indicating an autocrine/paracrine mechanism for the regulation of neutrophil inflammatory response by stress hormones. Strikingly, administration of NET components to mice induces depressive-like behavior. Moreover, activation of the glucocorticoid receptor in human volunteers leads to increase in gene expression of NET proteins. Furthermore, patients with major depressive disorder show gene upregulation of NET proteins. Our data highlights the bi-directional relationship between neuroendocrine processes and neutrophils that contribute to stress-induced increase in inflammation and the role of neutrophil inflammatory responses in propagation of behavioral changes following stress.

immunology↗

bioRxiv2025

Sex Differences in Plasma Levels of Endocannabinoids and Related Lipids Before and After acute and repeated mTBI: an exploratory study for plasma biomarkers for mTBI

Mild traumatic brain injury (mTBI) is common diagnosis across all age groups and while most symptoms resolve within a few weeks; between 10 and 25 percent of mTBI patients suffer long-term problems. Known as post-concussion syndrome (PCS), symptoms include headache, a range of cognitive deficits, and depression. Currently, there are no established treatments for PCS and no clear predictive biometrics to determine which patients are at increased risk. Previous studies have identified some protein-derived plasma biomarkers for mTBI, however, the effects of mTBI on lipid signaling molecules and metabolites in blood is largely unknown. Endogenous lipids (endolipids) such as the endocannabinoids (eCBs) and their congeners are lipid signaling molecules that are associated with promoting neuroprotective responses after head trauma in animal models. Here, we examine the plasma lipidome using a rat model of acute and repeated mTBI that we previously demonstrated had a sex dependent change in neuroinflammation wherein females showed a higher degree of neurodegeneration after repeated head-injury than males. Key results of this exploratory lipidomics screen here demonstrates that acute head injury drives significantly more changes in plasma endolipids in males (32%) than females (8%), whereas, on the second day of head injury, only 11% change in males but 15% in females. Some key endolipids were modified in both males are precursors for resolving molecules and this was lacking in females. Given that females with repeated mTBI in this model demonstrated aspects of PCS, this could be an important component in evaluating clinical cases. Endolipids in the screen were measurable in plasma using only 100{micro}L, a volume necessary to be able to perform multiple blood draws on these rodent subjects. This threshold provides evidence that the levels of these endolipids could be readily measured throughout a patients recovery. Therefore, this family of endolipids has the potential to provide data on the progression of the injury and could be another crucial aspect in predicting mTBI outcomes.

neuroscience↗

bioRxiv2025

The MicroMap is a network visualisation resource for microbiome metabolism

The human microbiome plays a crucial role in metabolism and thereby influences health and disease. Constraint-based reconstruction and analysis (COBRA) has proven an attractive framework to generate mechanism-derived hypotheses along the nutrition-host-microbiome-disease axis within the computational systems biology community. Unlike for human, no large-scale visualisation resource for microbiome metabolism has been available to date. To address this gap, we created the MicroMap, a manually curated microbiome metabolic network visualisation, which captures the metabolic content of over a quarter million microbial genome-scale metabolic reconstructions. The MicroMap contains 5,064 unique reactions and 3,499 unique metabolites, including for 98 drugs. The MicroMap allows users to intuitively explore microbiome metabolism, inspect microbial metabolic capabilities, and visualise computational modelling results. Further, the MicroMap shall serve as an educational tool to make microbiome metabolism accessible to broader audiences beyond computational modellers. For example, we utilised the MicroMap to generate a comprehensive collection of 257,429 visualisations, corresponding to the entire scope of our current microbiome reconstruction resources, to enable users to visually compare and contrast the metabolic capabilities for diaerent microbes. The MicroMap seamlessly integrates with the Virtual Metabolic Human (VMH, www.vmh.life) and the COBRA Toolbox (opencobra.github.io), and is freely accessible at the MicroMap dataverse (https://dataverse.harvard.edu/dataverse/micromap), in addition to all the generated reconstruction visualisations.

systems biology↗

bioRxiv2025

Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats.

Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Females were significantly more sensitive to the 0.3 mg/kg dose of psilocybin than males. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli such as the claustrum and the cortico-basal ganglia-thalamic-cortical loop were all affected by psilocybin in a dose-dependent manner. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.

neuroscience↗

bioRxiv2017

Novel Magnetic Resonance Imaging strategy targeting Neurotensin Receptors in detection of Prostate Cancer

Prostate cancer is the second leading cause of all male cancer deaths. One of the factors present in malignant prostate cells and shown to support its metastatic growth is the neuropeptide neurotensin (NT). The primary goal of the present study was to establish the feasibility of using a newly developed paramagnetic receptor ligand for NT and non-invasive ultrahigh-field magnetic resonance (MR) imaging to visualize prostate cancer in rodents. Orthotropic xenografts were initiated in six-week old male BALB/c nu/nu athymic mice (n = 28) by intra-prostatic (ventral lobe) inoculation of human prostate cancer cells (10L of PC3 cells (106 /100l)). Palpable tumors developed within 30-60 days. A micro-imager utilized in these studies was an actively shielded 9.4T, 89 mm bore, Oxford superconducting magnet with a 100 gauss/cm gradient system. Prior to contrast injection, T2 weighted anatomy scans were done to localize the tumor with a spin-echo multi-slice sequence with TR: 2000 TE: 40 and NEX: 1 in both coronal and axial planes. The paramagnetic ligand data sets were collected with a spin-echo, T1 weighted pulse sequence (MSME): TR 300 msec; TE 5 msec; NEX 4 in both axial and coronal planes. The data sets were taken initially at 5-min intervals post contrast injection for the first half hour and then at 15 min intervals for the next 1.5-2 hours for a time series analyses. The temporal distribution of MR signal intensity in various regions were determined in the absence and presence of NT. Our results confirm that the novel NT molecule was protected from enzymatic degradation and capable of forming a high affinity paramagnetic NT ligand with an extended half-life. During the imaging studies, the signal intensity increased by 200 % in the region of the tumor. This increase in signal intensity approached maximum binding within 30 minutes and remained visible for 1 hour post-injection of the contrast agent. Taken together, these findings suggest that it is feasible to detect and image prostate cancer using a paramagnetic NT ligand and the emergence of the NT receptor ligand that may be used as a diagnostic marker for prostate cancer in humans.

cancer biology↗