Biology subjects

Rezaei, S.

Publications and source records attributed to Rezaei, S..

9 recordsLinked to original sources

bioRxiv2026

Dual Roles of Interferon-γ Receptor in Somatostatin Interneurons at Baseline and During Inflammation

Background: Neuropsychiatric disorders such as major depressive disorder show converging evidence of gamma-aminobutyric acid (GABA) dysfunction, including consistent reductions in somatostatin (SST) interneuron markers. SST interneurons are selectively vulnerable to inflammation, yet the underlying mechanisms remain unclear. Interferon-gamma (IFN-{gamma}), a pro-inflammatory cytokine implicated in mood and anxiety disorders, signals through the IFN-{gamma} receptor (IFNGR), which is expressed in neurons. We tested whether IFNGR signaling in SST interneurons regulates anxiety-like and cognitive behavior and prevents inflammation-induced molecular deficits. Methods: We generated mice with conditional deletion of IFNGR from SST cells and assessed anxiety-like behavior using elevated plus maze and working memory using Y-maze at baseline and after lipopolysaccharide (LPS) induced inflammation. Expression of SST-related, neurotrophic, synaptic, and glial markers was quantified. Results: At baseline and after LPS-induced inflammation, IFNGR deletion in SST cells increased anxiety-like behavior without affecting working memory. In control mice, LPS reduced Sst (p=0.0006), neuropeptide Y (Npy) (p=0.0022), brain-derived neurotrophic factor (Bdnf) (p<0.0001), and synapsin 1 (Syn1) (p=0.0150); these reductions were not significant in mice lacking IFNGR in SST cells. Knockouts also showed lower baseline Bdnf, Syn1, Gephyrin (Gphn), and allograft inflammatory factor 1 (Aif1, encoding Iba1) than controls. Conclusions: IFNGR signaling in SST cells plays a dual role: supporting normal behavior and molecular homeostasis while mediating LPS-induced molecular deficits. These findings link immune signaling to the GABAergic dysfunction implicated in major depressive disorder and suggest IFNGR signaling in SST cells may regulate cortical microcircuit integrity at baseline and during inflammatory challenge.

neuroscience↗

bioRxiv2026

Natural microbial exposure imposes layered constraints on epithelial and type 2 immunity

The tuft cell-ILC2 amplification circuit has emerged as a central paradigm of anti-helminth immunity in laboratory animals, driving the so-called weep and sweep response, required for parasite expulsion. Yet soil-transmitted helminths (STHs) commonly establish chronic infections in humans. Whether tuft cell expansion is required for parasite clearance under naturalistic conditions remains unknown. Here, using wildlings, a naturalized mouse model exposed from birth to complex microbial communities and pathogens, we re-investigated anti-STH immunity in the context of ecological realism. Following infection with Nippostrongylus brasiliensis, specific pathogen-free (SPF) mice mounted markedly amplified type 2 responses in both lung and intestine compared to wildlings. In the intestine, SPF mice mounted robust tuft cell expansion, IL-25 production, ILC2 accumulation, and goblet cell hyperplasia. In contrast, infected wildlings exhibited delayed parasite expulsion, limited tuft cell expansion, reduced IL-25 and ILC2 responses, and attenuated goblet cell expansion. Wildling tuft cells, but not goblet cells, displayed markedly reduced expansion in response to succinate or exogenous IL-13, indicating selective hypo-responsiveness of the epithelial sensory compartment. Microbial transfer into adult SPF mice selectively conferred tuft cell hypo-responsiveness without impairing ILC2 accumulation or goblet cell expansion. Tuft cell hypo-responsiveness in wildlings and FMT recipients was associated with enrichment of fermentative bacteria and increased levels of the short chain fatty acids acetate and propionate. Together, these findings indicate that ecological microbial exposure imprints systemic type 2 immunity during early-life, whereas epithelial responsiveness remains plastic and microbiome-dependent, thereby revealing regulatory constraints not evident under SPF conditions. One Sentence SummaryOur findings reveal that in a naturalized immune-microbiome context, intestinal tuft cells are surprisingly hypo-responsive, highlighting how environmental microbial exposure can calibrate type 2 immunity and helminth resistance.

immunology↗

bioRxiv2025

Synthesizing unmodified, supercoiled circular DNA molecules in vitro

Supercoiled (Sc) circular DNA, such as plasmids, has shown therapeutic potential since the 1990s, but is limited by bacterial modifications, unnecessary DNA sequences, and contaminations that may trigger harmful responses. To overcome these challenges, we have developed two novel scalable biochemical methods to synthesize unmodified Sc circular DNA. Linear DNA with two loxP sites in the same orientation is generated via PCR or rolling circle amplification. Cre recombinase then converts this linear DNA into relaxed circular DNA. After T5 exonuclease removes unwanted linear DNA, topoisomerases are employed to generate Sc circular DNA. We have synthesized EGFP-FL, a 2,002 bp mini-circular DNA carrying essential EGFP expression elements. EGFP-FL transfected human HeLa and mouse C2C12 cells with much higher efficiency than E. coli-derived plasmids. These new biochemical methods can produce unmodified Sc circular DNA, in length from 196 base pairs to several kilobases and in quantities from micrograms to milligrams, providing a promising platform for diverse applications.

biochemistry↗

bioRxiv2025

Scaly-Tail Organ Enhances Static Stability during Pel's Scaly-tailed Flying Squirrels' Arboreal Locomotion

Scaly-tailed squirrels (Anomaluridae) are one of the least studied mammalian families. Their namesake is due to a peculiar and unique scaly-tail organ extruding from the caudal vertebrate that has been predicted to help reduce skidding. This study investigates the function of the scaly-tail organ found in Anomalurus pelii, investigating its potential role in enhancing arboreal locomotion. As these animals glide from tree to tree in a habitat abundant with smooth-bark trees, we hypothesize that the scaly-tail organ assists with friction enhancement in their native smooth-bark habitat. Through a combination of analyses using mathematical and physical models for experimental validation, we explore whether the scaly-tail organ could improve the sliding and overturning stability during perching. Our experimental results showed that the scaly-tail organ can act as a skid-reduction mechanism by enhancing substrate engagement on intermediate roughness substrates by 58%. Mathematical models showed the scaly-tail organ enhances overturning stability by acting as an additional support point. Our model showed that the scaly-tailed squirrel can reach up to 82.5{whitebullet} inclination without claw force; however, without scales, it reduces to 79.6{whitebullet}. Overall, this research highlights the functional significance of scaly-tail organs in adaptations in scaly-tailed flying squirrels and contributes to our understanding of their locomotion strategies and environmental stresses. Our study also provides insights into innovative perching mechanisms for robots operating in arboreal environments.

bioengineering↗

bioRxiv2024

Optimization of Seizure Prevention by Cannabidiol (CBD)

ObjectiveCannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived, pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study. MethodsWe evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral and injection routes. We used CBD broad spectrum (inhaled and injection) versus CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring Immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups. ResultsOur findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested. CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (p<0.05) compared to other forms of CBD treatments. ConclusionOur data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, warrants further research.

neuroscience↗

bioRxiv2024

Repetitive Learning Control for Body Caudal Undulation with Soft Sensory Feedback

Soft bio-inspired robotics is a growing field of research that seeks to close the gap with animal robustness and adaptability where conventional robots fall short. The embedding of sensors with the capability to discriminate between different body deformation modes is a key technological challenge in soft robotics to enhance robot control - a difficult task for such kinds of systems with high degrees of freedom. The recently conceived Linear Repetitive Learning Estimation Scheme (LRLES) - to be included in the traditional Proportional Integral Derivative (PID) control - is proposed here as a way to compensate for uncertain dynamics on a soft swimming robot, which is actuated with soft pneumatic actuators and equipped with soft sensors providing proprioceptive information pertaining to lateral body caudal bending akin to a goniometer. The proposed controller is derived in detail and experimentally validated, with the experiment consisting of tracking a desired trajectory for bending angle while continuously oscillating with a constant frequency. The results are compared vis a vis those achieved with the traditional PID controller, finding that the PID endowed with the LRLES outperforms the PID controller (though the latter has been separately tuned) and experimentally validating the novel controllers effectiveness, accuracy, and matching speed.

bioinformatics↗

bioRxiv2023

LPS-Induced Inflammation Reduces GABAergic Interneuron markers and Brain-derived Neurotrophic Factor in Mouse Prefrontal Cortex and Hippocampus

Inflammation, reduced gamma-aminobutyric acidergic (GABAergic) function and altered neuroplasticity are co-occurring pathophysiologies in major depressive disorder (MDD). However, the link between these biological changes remains unclear. We hypothesized that inflammation induces deficits in GABAergic interneuron markers and that this effect is mediated by brain-derived neurotrophic factor (BDNF). We report here that systemic inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) (0.125, 0.25, 0.5, 1, 2mg/kg) in the first cohort of C57BL/6 mice (n=72; 9-12 weeks; 50% female) resulted in increased interleukin 1-beta and interleukin-6 in prefrontal cortex (PFC) and hippocampus (HPC), as measured using enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase reaction (qPCR) was used to explore the effect of LPS on the expression of GABAergic interneuron markers. In the PFC of the second cohort (n=39; 9-12 weeks; 50% female), 2mg/kg of LPS decreased the expression of somatostatin (Sst) (p=0.0014), parvalbumin (Pv) (p=0.0257), cortistatin (Cort) (p=0.0003), neuropeptide Y (Npy) (p=0.0033) and cholecystokinin (Cck) (p=0.0041), and did not affect corticotropin-releasing hormone (Crh) and vasoactive intestinal peptide (Vip) expression. In the HPC, 2mg/kg of LPS decreased the expression of Sst (P=0.0543), Cort (p=0.0011), Npy (p=0.0001), and Cck (p<0.0001), and did not affect Crh, Pv, and Vip expression. LPS decreased the expression of Bdnf in the PFC (P<0.0001) and HPC (P=0.0003), which significantly correlated with affected markers (Sst, Pv, Cort, Cck, and Npy). Collectively, these results suggest that inflammation may causally contribute to cortical cell microcircuit GABAergic deficits observed in MDD.

neuroscience↗

bioRxiv2023

Machine Learning to Identify Molecular Markers for Metabolic Disease Development Using Mouse Models

BackgroundAging, Western diet (WD) intake, and bile acid (BA) receptor farnesoid X receptor (FXR) inactivation are risk factors for metabolic disease development including nonalcoholic fatty liver disease (NAFLD) and chronic inflammation-related health issues such as dementia. The progression of the metabolic disease can be escalated when those risks are combined. Inactivation of FXR is cancer prone in both humans and mice. The current study used omics data generated within the gut-liver axis to classify those risks using bioinformatics and machine learning approaches. MethodsDifferent ages (5, 10, and 15 months) of wild-type (WT) and FXR knockout (KO) male mice were fed with either a healthy control diet (CD) or a WD since weaning. Hepatic transcripts, liver, serum, and urine metabolites, hepatic bile acids (BAs), as well as gut microbiota were used for risk prediction. A linear support vector machine with K-fold cross-validation was used for classification and feature selection. ResultsIncreased urine sucrose alone achieved 91% accuracy in predicting WD intake. Hepatic lithocholic acid (LCA) and serum pyruvate had 100% and 95% accuracy, respectively to classify age. Association analyses showed hepatic LCA was positively associated with serum concentrations of acetone, a ketone body, and 1,3-dihydroxyacetone (DHA), but negatively correlated with serum pyruvate. Urine metabolites (decreased creatinine and taurine as well as increased succinate) or gut microbiota (increased Dorea, Dehalobacterium, and Oscillospira) could predict FXR functional status with greater than 90% accuracy. Integrated pathway analyses revealed that the predictors for diet and FXR expression were implicated in the central carbon metabolism in cancer. To assess the translational relevance, mouse hepatic transcripts were crosschecked with human NAFLD and hepatocellular carcinoma (HCC) datasets. WD-affected hepatic Cyp39a1 and Gramd1b expression were associated with human HCC and NAFLD, respectively. The metabolites and diseases interaction analyses uncovered that the identified features are implicated in human metabolic diseases, mental disorders, and cancer. ConclusionThe risk prediction using mouse models contributes to the identification of noninvasive biomarkers for early diagnosis of metabolic disease development.

bioinformatics↗

bioRxiv2020

Comparative Neuroanatomy of the Lumbosacral Spinal Cord of the Rat, Cat, Pig, Monkey, and Human

The overall goal of this work was to create a high-resolution MRI atlas of the lumbosacral enlargement of the spinal cord of the rat (Sprague-Dawley), cat, domestic pig, rhesus monkey, and human. These species were chosen because they are commonly used in basic and translational research in spinal cord injuries and diseases. Six spinal cord specimens from each of the studied species (total of 30 specimens) were fixed, extracted, and imaged. Sizes of the spinal cord segments, cross-sectional dimensions, and locations of the spinal cord gray and white matter were quantified and compared across species. The obtained atlas establishes a reference for the neuroanatomy of the intact lumbosacral spinal cord in these species. It can also be used to guide the planning of surgical procedures of the spinal cord, technology design and development of spinal cord neuroprostheses, and the precise delivery of cells/drugs into target regions within the spinal cord parenchyma.

neuroscience↗