Biology subjects

Gorantla, N.

Publications and source records attributed to Gorantla, N..

5 recordsLinked to original sources

bioRxiv2025

Non-linear Age-related Change in Human Interleukin-11 and the receptor subunit alpha DNA Methylation

IntroductionInterleukin-11 (IL-11) is a cytokine involved in inflammatory processes and a previous study showed that blocking or knocking down IL11 in mice prolongs a healthy lifespan. This study investigates DNA methylation (DNAm) changes in the IL11 and IL-11 receptor subunit alpha (IL-11RA) gene across ages to reveal how aging might influence IL-11 production and sensitivity. MethodsA genome-wide DNAm database focusing on Cytosine-phosphate-Guanine (CpG) sites within the IL11 and IL11RA was analyzed. Hierarchical regression analyses examined the relationship between DNAm, age, and the squared age term for quadratic associations. ResultsThe database comprised 10,297 samples (5,156 males and 5,141 females) with a mean age of 53.9 years (SD = 14.1 years). The majority of IL11 and IL11RA CpG sites in the TSS1500 and 3UTR regions exhibited significant inverse U-shaped associations with age. DNAm levels were low during youth, increased in middle age (40s-50s), and decreased again in older age. ConclusionThe observed inverse U-shaped DNAm patterns in the IL11 and IL11RA suggest n non-linear, age-related regulation of IL-11 expression and sensitivity. These findings indicate that IL-11 may have different roles across life stages and suggest that therapeutic interventions targeting IL-11 should consider age-specific effects.

genetics↗

bioRxiv2025

Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients

Post-operative delirium (POD) is a common complication after surgery especially in elderly patients, characterized by acute disturbances in consciousness and cognition, which negatively impacts long-term outcomes. Effective treatments remain elusive due to the unclear pathophysiology of POD. To address the knowledge gap, we investigated DNA methylation profiles and gene expression changes in brain cells from POD and non-POD patients who underwent brain resection surgery for medication refractory epilepsy. DNA methylation analysis revealed alteration in epigenetic status of immune and inflammation-related genes. Single-nucleus RNA sequencing (snRNAseq) identified POD-specific glial cell alterations, particularly in microglia, where neuroinflammation was strongly enhanced, consistent with epigenetic findings. Astrocytes exhibited changes in synapse-related functions and migration. Furthermore, downstream analysis indicated similarities between POD-associated glial cell states and pathologies such as encephalitis and dementia. Overall, this study--the first multi-omics analysis of brain tissue from POD patients--provides direct evidence of glial cell contributions to POD pathogenesis, and highlights potential therapeutic targets.

neuroscience↗

bioRxiv2025

The age-related susceptibility to postoperative delirium quantified by bispectral electroencephalography (BSEEG) correlates with postoperative delirium-like behavior in mice

Postoperative delirium (POD) is a severe neuropsychiatric state characterized by acute fluctuating various mental symptoms. Despite its prevalence, the underlying mechanisms of POD remain largely unknown, and effective biomarkers for its detection are lacking. We have successfully developed a novel delirium detection method, the bispectral electroencephalography (BSEEG) method, which has shown excellent performance in delirium detection and outcome prediction. From there, similar to the clinical situation, we hypothesize that BSEEG scores can serve as indicators of POD-like states in mice. This study investigated the correlation between POD-like behavior and BSEEG score in a mouse model following EEG head mount implantation surgery. 2-3 and 22-23 month-old male C57BL/6J mice underwent EEG head-mount implantation surgery, followed by EEG monitoring and a battery of behavioral tests, including Buried Food Test, Open Field Test, and Y-maze, to assess POD-like behavior. We measured BSEEG scores and analyzed the correlation between these scores and the behavior measurements. The results showed that BSEEG scores correlated with attention deficit and decreases in locomotor activity in young mice, whilst BSEEG scores only correlated with a decrease in locomotor activity in aged mice. Notably, composite Z scores representing delirium severity also showed a correlation with BSEEG scores in young mice. Our findings indicate that the BSEEG method can be an indicator of POD-like states consistent with those measured by behavior tests. This study provides a novel preclinical framework for understanding the pathophysiology of POD and underscores the potential of BSEEG as a valuable tool for delirium detection and severity assessment.

animal behavior and cognition↗

bioRxiv2024

LPS-induced delirium-like behavior and microglial activation in mice correlate with bispectral electroencephalography (BSEEG)

Delirium is a multifactorial medical condition characterized by impairment across various mental functions and is one of the greatest risk factors for prolonged hospitalization, morbidity, and mortality. Research focused on delirium has proven to be challenging due to a lack of objective measures for diagnosing patients, and few laboratory models have been validated. Our recent studies report the efficacy of bispectral electroencephalography (BSEEG) in diagnosing delirium in patients and predicting patient outcomes. We applied BSEEG to validate a lipopolysaccharide (LPS)-induced mouse model of delirium. Moreover, we investigated the relationship between BSEEG score, delirium-like behaviors, and microglia activation in hippocampal dentate gyrus and cortex regions in young and aged mice. There was a significant correlation between BSEEG score and impairment of attention in young mice. Additionally, there was a significant correlation between BSEEG score and microglial activation in hippocampal dentate gyrus and cortex regions in young and aged mice. We have successfully validated the BSEEG method by showing its associations with a level of behavioral change and microglial activation in an LPS-induced mouse model of delirium. In addition, the BSEEG method was able to sensitively capture an LPS-induced delirium-like condition that behavioral tests could not capture because of a hypoactive state.

neuroscience↗

bioRxiv2023

Engineering luminopsins with improved coupling efficiencies

SignificanceLuminopsins (LMOs) are bioluminescent-optogenetic tools with a luciferase fused to an opsin that allow bimodal control of neurons by providing both optogenetic and chemogenetic access. Determining which design features contribute to the efficacy of LMOs will be beneficial for further improving LMOs for use in research. AimWe investigated the relative impact of luciferase brightness, opsin sensitivity, pairing of emission and absorption wavelength, and arrangement of moieties on the function of LMOs. ApproachWe quantified efficacy of LMOs through whole cell patch clamp recordings in HEK293 cells by determining coupling efficiency, the percentage of maximum LED induced photocurrent achieved with bioluminescent activation of an opsin. We confirmed key results by multielectrode array (MEAs) recordings in primary neurons. ResultsLuciferase brightness and opsin sensitivity had the most impact on the efficacy of LMOs, and N-terminal fusions of luciferases to opsins performed better than C-terminal and multi-terminal fusions. Precise paring of luciferase emission and opsin absorption spectra appeared to be less critical. ConclusionsWhole cell patch clamp recordings allowed us to quantify the impact of different characteristics of LMOs on their function. Our results suggest that coupling brighter bioluminescent sources to more sensitive opsins will improve LMO function. As bioluminescent activation of opsins is most likely based on Forster resonance energy transfer (FRET), the most effective strategy for improving LMOs further will be molecular evolution of luciferase-fluorescent protein-opsin fusions.

molecular biology↗