Cortical Cells Research Articles

RhoA regulates oligodendrocyte differentiation and myelination by orchestrating cortical and membrane tension.

Timely differentiation and myelin formation by oligodendrocytes are essential for the physiological functioning of the central nervous system (CNS). While the Rho GTPase RhoA has been hinted as a negative regulator of myelin sheath formation, the precise in vivo mechanisms have remained elusive. Here we show that RhoA controls the timing and progression of myelination by oligodendrocytes through a fine-tuned balance between cortical tension, membrane tension and cell shape. Using a conditional mouse model, we observe that Rhoa ablation results in the acceleration of myelination driven by hastened differentiation and facilitated through membrane expansion induced by changes in MLCII activity and in F-actin redistribution and turnover within the cell. These findings reveal RhoA as a central molecular integrator of alterations in actin cytoskeleton, actomyosin contractility and membrane tension underlying precise morphogenesis of oligodendrocytes and normal myelination of the CNS.

New magnetic iron nanoparticle doped with selenium nanoparticles and the mechanisms of their cytoprotective effect on cortical cells under ischemia-like conditions

Ischemic stroke is the cause of high mortality and disability Worldwide. The material costs of stroke treatment and recovery are constantly increasing, making the search for effective and more cost-effective treatment approaches an urgent task for modern biomedicine. In this study, iron nanoparticles doped with selenium nanoparticles, FeNP@SeNPs, which are three-layered structures, were created and characterized using physical methods. Fluorescence microscopy, inhibitor and PCR analyzes were used to determine the signaling pathways involved in the activation of the Ca2+ signaling system of cortical astrocytes and the protection of cells from ischemia-like conditions (oxygen-glucose deprivation and reoxygenation). In particular, when using magnetic selenium nanoparticles together with electromagnetic stimulation, an additional pathway for nanoparticle penetration into the cell is activated through the activation of TRPV4 channels and the mechanism of their endocytosis is facilitated. It has been shown that the use of magnetic selenium nanoparticles together with magnetic stimulation represents an advantage over the use of classical selenium nanoparticles, as the effective concentration of nanoparticles can be reduced many times over.

Astrocyte-derived factors regulate CNS myelination.

The role that astrocytes play in central nervous system (CNS) myelination is poorly understood. We investigated the contribution of astrocyte-derived factors to myelination and revealed a substantial overlap in the secretomes of human and rat astrocytes. Using in vitro myelinating co-cultures of primary retinal ganglion cells and cortical oligodendrocyte precursor cells, we discovered that factors secreted by resting astrocytes, but not reactive astrocytes, facilitated myelination. Soluble brevican emerged as a new enhancer of developmental myelination in vivo, CNS and its absence was linked to remyelination deficits following an immune-mediated damage in an EAE mouse model. The observed reduction of brevican expression in reactive astrocytes and human MS lesions suggested a potential link to the compromised remyelination characteristic of neurodegenerative diseases. Our findings suggested brevican's role in myelination may be mediated through interactions with binding partners such as contactin-1 and tenascin-R. Proteomic analysis of resting versus reactive astrocytes highlighted a shift in protein expression profiles, pinpointing candidates that either facilitate or impede CNS repair, suggesting that depending on their reactivity state, astrocytes play a dual role during myelination.

Functional diversities within neurons and astrocytes in the adult rat auditory cortex revealed by single-nucleus RNA sequencing

The mammalian cerebral cortex is composed of a rich diversity of cell types. Sensory cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions for perception, learning, and memory. The auditory cortex (AC) has been most extensively studied for its experience-dependent effects, including for perceptual learning and associative memory. Here, we used single-nucleus RNA sequencing (snRNA-seq) in the AC of the adult rat to investigate the breadth of transcriptionally diverse cell types that likely support the role of AC in experience-dependent functions. A variety of unique excitatory and inhibitory neuron subtypes were identified that harbor unique transcriptional profiles of genes with putative relevance for the adaptive neuroplasticity of cortical microcircuits. In addition, we report for the first time a diversity of astrocytes in AC that may represent functionally unique subtypes, including those that could integrate experience-dependent adult neuroplasticity at cortical synapses. Together, these results pave the way for building models of how cortical neurons work in concert with astrocytes to fulfill dynamic and experience-dependent cognitive functions.

Identification of the proliferative activity of germline progenitor cells in the adult ovary of the bat Artibeus jamaicensis.

Until a few years ago, it was assumed that oocyte renewal did not take place in the ovary of adult organisms; however, the existence of germline progenitor cells (GPCs), which renew the ovarian follicular reserve, has now been documented in mammals. Specifically, in the adult ovary of bats, the presence of cells located in the cortical region with characteristics similar to GPCs, called adult cortical germ cells (ACGC), has been observed. One of the requirements that a GPC must fulfil is to be able to proliferate mitotically, so the evaluation of cell proliferation in ACGC is of utmost importance in order to be able to relate them to a parental lineage. Currently, there are several methods to determine cell proliferation, including BrdU labelling or the use of endogenous proliferation markers. Thus, the aim of this work was to evaluate the proliferative activity of ACGC in the adult ovary of the bat Artibeus jamaicensis, using different proliferation markers and correlating these with the protein expression of the transcription factor Oct4 and the germ line marker Ddx4. We found that the expression pattern of the proliferation markers BrdU, PCNA, Ki-67 and pH3 occurs at different times of the cell cycle, so co-localization of two or more of these markers allows us to identify proliferating cells. This allowed us to identify ACGC with proliferative capacity in the adult ovary of A. jamaicensis, suggesting that GPCs renew the follicle reserve during the adult life of the organism.

Intravenous chaperone treatment of late-stage Alzheimer´s disease (AD) mouse model affects amyloid plaque load, reactive gliosis and AD-related genes

Treatment strategies that are efficient against established Alzheimer’s disease (AD) are needed. BRICHOS is a molecular chaperone domain that prevents amyloid fibril formation and associated cellular toxicity. In this study, we treated an AD mouse model seven months after pathology onset, using intravenous administration of recombinant human (rh) Bri2 BRICHOS R221E. Two injections of rh Bri2 BRICHOS R221E per week for three months in AD mice reduced amyloid β (Aβ) burden, and mitigated astro- and microgliosis, as determined by glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba1) immunohistochemistry. Sequencing of RNA from cortical microglia cells showed that BRICHOS treatment normalized the expression of identified plaque-induced genes in mice and humans, including clusterin and GFAP. Rh Bri2 BRICHOS R221E passed the blood–brain barrier (BBB) in age-matched wild-type mice as efficiently as in the AD mice, but then had no effect on measures of AD-like pathology, and mainly affected the expression of genes that affect cellular shape and movement. These results indicate a potential of rh Bri2 BRICHOS against advanced AD and underscore the ability of BRICHOS to target amyloid-induced pathology.

Complex Brain Morphology Discovered in the Shark Parasite Nybelinia surmenicola (Cestoda: Trypanorhyncha).

The ultrastructure of the nervous system has been studied in sexually mature Nybelinia surmenicola (Cestoda: Trypanorhyncha) from the intestine of a shark Lamna ditropis. The central nervous system (CNS) reveals a complex organization within cestodes and corresponds to the trypanorhynch pattern of brain architecture. The brain of N. surmenicola is differentiated into nine clearly defined lobes and semicircular, median, and X-shaped cruciate commissures. A specific feature is the presence of a powerful extracellular capsule that surrounds the brain lobes with the cortical glial cells. Moreover, the architecture of the anterior lobes clearly distinguishes the species of Tentacularioidea. The neurons of the anterior lobes form compact groups looking like frontal horns. There are approximately 120 neurons in the anterior lobes and a preliminary estimate of more than 300 perikarya in the brain. Several ultrastructural types of neurons have been identified, differing in the size and shape of the soma, the density of the cytoplasm, and the ultrastructure of synaptic vesicles. Numerous synapses involving clear and electron-dense vesicles have been observed in neuropils. Two types of glial cells have been found in the brain that participate in neuronal metabolism and wrap around the giant axons, brain lobes, neuropil compartments, and the main nerve cords. Such a powerful extracellular fibrillar brain capsule has not been observed in the brain of other studied cestodes and has been demonstrated in this study for the first time. The differentiation of the brain lobes reveals the important role of the rhyncheal system in the evolution of cestodes and correlates with their behavior. The anterior nerves arising from the anterior lobes innervate the radial muscles stabilizing the position of the tentacle sheaths and movements of the attachment organs. The nervous system anatomy and the brain architecture may reflect the morphofunctional aspects of the tapeworm evolution.

The poplar SWEET1c glucose transporter plays a key role in the ectomycorrhizal symbiosis.

The mutualistic interaction between ectomycorrhizal fungi and trees is characterized by the coordinated exchange of soil nutrients with soluble sugars. Despite the importance of this process, the precise mechanism by which sugars are transported from host roots to colonizing hyphae remains unclear. This study aimed to identify the specific membrane transporters responsible for the unloading of sugars at the symbiotic interface, with a focus on the role of the root Sugars Will Eventually Be Exported Transporter (SWEET) uniporters. Our study used RNA sequencing and quantitative PCR to identify PtaSWEET gene expression in Populus tremula × alba-Laccaria bicolor ectomycorrhizal root tips. Our results suggest that symbiosis-induced PtaSWEET1c is primarily responsible for transporting glucose and sucrose, as demonstrated by the yeast assays. Moreover, we used a promoter-YFP reporter to confirm the localization of the PtaSWEET1c expression in cortical cells of ectomycorrhizal rootlets, supporting its major role in supplying glucose at the symbiotic interface. Furthermore, our observations confirmed the localization of PtaSWEET1c-GFP in the plasma membrane. The inactivation of PtaSWEET1c reduced ectomycorrhizal root formation and 13C translocation to ectomycorrhizal roots. Our findings highlight the crucial role of PtaSWEET1c in facilitating glucose and sucrose transport at the symbiotic interface of Populus-L. bicolor symbiosis.

Serotonin-2B receptor (5-HT2BR) expression and binding in the brain of APPswe/PS1dE9 transgenic mice and in Alzheimer’s disease brain tissue

Despite well-documented dysregulation in central serotonergic signaling in Alzheimer’s disease (AD), knowledge about the potential involvement of the serotonin-2B receptor (5-HT2BR) subtype remains sparse. Here, we assessed the levels of 5-HT2BRs in brain tissue from APPswe/PS1dE9 transgenic (TG) mice, AD patients, and adult microglial cells. 5-HT2BR mRNA was measured by RT-qPCR in ageing TG and wild-type (WT) mice, in samples from the middle frontal gyrus of female, AD and control subjects, and in microglia from the cerebral cortex of WT mice. The density of 5-HT2BRs was measured by autoradiography using [3H]RS 127445. Both mouse and human brains had low levels of 5-HT2BR mRNA. In whole-brain mouse samples, mRNA expression was significantly lower in TG mice compared to WT at > 18 months of age. In the Aβ-plaque-burdened neocortex and hippocampus of old TG mice, however, levels of 5-HT2BR mRNA were two-fold higher over control, with similar elevations observed in the Aβ-plaque-burdened frontal cortex of human AD patients. 5-HT2BR mRNA expression varied widely in adult microglia and was higher compared to other cortical cell subtypes. In mice, specific [3H]RS-127445 binding in the cortex was first detected after 3 months of age. The density of 5-HT2BRs was low and overall reduced in TG, compared to WT mice. Binding was detectable but too low to be reliably quantified in the human cortex. Our results document Aβ-associated increases in 5-HT2BR mRNA expression and suggest reduced receptor binding in the context of AD. Studies investigating the functional involvement of microglial 5-HT2BRs in AD are considered relevant.

Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues.

Current methods for analyzing chromatin architecture are not readily scalable to heterogeneous tissues. Here we introduce Droplet Hi-C, which uses a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture of the mouse cortex and analyzed gene regulatory programs in major cortical cell types. In addition, we used this technique to detect copy number variations, structural variations and extrachromosomal DNA in human glioblastoma, colorectal and blood cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We refined the technique to allow joint profiling of chromatin architecture and transcriptome in single cells, facilitating exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C both addresses critical gaps in chromatin analysis of heterogeneous tissues and enhances understanding of gene regulation.

Associations of Arbuscular Mycorrhizal Fungi (AMF) for Enhancements in Soil Fertility and Promotion of Plant Growth: A Review

Arbuscular Mycorrhizal Fungi are used for soil fertility enhancements and stimulating plant growth in which they association with other organisms like terrestrial plants. Mycorrhizas create an association between fungi and the roots of plants. Therefore, the review was made to point out important fungal species involved in fungal plant interaction and their major roles in agriculture as well as ecosystem. 80% of plants form associations with mycorrhizal fungi. The fungal are used to use their different organs like chain, arbuscular, vesicle, supportive cells and spore to interact with the other plant/ plat’s organ. The mycorrhizal fungi can be categorized into two principal classifications based on their anatomical interactions with the roots of host plants. Arbuscular Mycorrhizal and Ectomycorrhizal fungi utilize two distinct strategies for nutrient acquisition. The main categories of vesicular arbuscular mycorrhizal associations are linear or coiling and of ectomycorrhizal associations are epidermal or cortical. The rhizospheric and endophytic microbes promote plant growth as inoculated with crop. AM fungi as an obligate symbiont share a distinct feature called arbuscules as a site of nutrient exchanges between host and fungi. Arbuscules developed between cell wall and plasma membrane of root cortical cells and differentiated from plant plasma membrane by periarbuscular membrane. Arbuscular mycorrhizal fungi (AMF) play an indispensable role in augmenting plant nutrient acquisition, enhancing plant resilience and tolerance to various environmental stresses, improving soil fertility and structure, and providing numerous beneficial effects. AMF engage in interactions with other soil microorganisms, such as plant growth-promoting rhizobacteria, resulting in a synergistic effect that promotes plant growth and offers protection against pathogens associated with Rhizobia. Both AMF and Rhizobia utilize the same signaling pathways, which facilitate their association with host plants and enable nitrogen fixation within the soil ecosystem. A positive relationship has been established between AMF colonization and the diversity of soil microbial communities. Nitrogen-fixing rhizobia, mycorrhizal fungi, and root nodule symbioses typically exhibit synergistic interactions concerning infection rates and their effects on mineral nutrition and plant growth, thereby significantly enhancing the status of soil fertility, particularly with respect to soil quality characteristics.

P18.42.B TAU AND AMYLOID BETA PATHOLOGY IN IDH-MUTANT GLIOMA

Abstract BACKGROUND With an aging population the incidence of brain tumors and neurodegenerative diseases is increasing. Although biological associations between glioma and Alzheimer’s disease (AD) have been suggested, the frequency of comorbidity is insufficiently defined. We here screen tumor-adjacent cortex of a representative cohort of patients with low grade glioma for AD neuropathological changes (ADNC) specifically for phosphorylated tau (pTau) and amyloid beta (Abeta) deposition, microglial activation, amyloid precursor protein (APP) expression, diffuse axonal injury, and cortical tumor cell infiltration. MATERIAL AND METHODS A total of 85 patients with astrocytoma, IDH mutant, CNS-WHO grade 2-3, (N=37, median age: 39) and oligodendroglioma, IDH mutant and 1p-19q co-deleted, CNS-WHO grades 2-3 (N=48 median age: 50) were included. 2µm sections were immunohistochemically stained for the markers b-A4, t-AT8, NeuN, APP and Iba1. Whole slide quantification was performed using Matlab and QuPath codes. For a subset of 15 patients, longitudinal samples were available for analysis of post-treatment effects. RESULTS The median cell density in the tumor-adjacent cortex was 1355/mm2 for astrocytoma and 1392/mm2 for oligodendroglioma, which was significantly higher than in non-tumor infiltrated cortex (median: 1030 cells/mm², p-value<0.0001). A total of 32 patients (38%) showed Abeta (14%, n=12/85) and/or pTau pathology (36%, n=31/85) in the tumor-adjacent cortex. No difference between astrocytoma and oligodendroglioma was reported. ADNC was mostly frequently observed in older patients but was also present in young individuals (median: 34 years, range: 17 to 77 years). pTau was significantly positively correlated with tumor cell infiltration (Kendall´s tau=0.13, p=0.002). Both Abeta and pTau deposits were frequently observed in the frontal cortex (30%, N=18/60). The tumor infiltration into the cortical regions was associated with neuronal loss (Kendall´s tau=-0.29, p<0.0001). Microglial activation depended on the degree of tumor infiltration (R=0.29), followed by increasing patient age (R=0.12). Diffuse axonal injury was associated with ADNC (Chi²=19.6, p<0.05). APP expression of tumor cells was highest in patients of old age (R=0.35). Longitudinal samples showed stable ANDC pathology in 15/15 subjects. CONCLUSION Our preliminary findings suggest presence of ADNC in roughly a third of patients with low-grade glioma, which increases with tumor cell infiltration into the cortex, microglial activation and patient age. Notably, isolated pTau pathology was more pronounced than Abeta pathology suggesting the acquisition of a secondary tauopathy.

Evidence for the proposal that Palisada corallopsis and P. furcata (Ceramiales, Rhodophyta) are conspecific

Abstract Palisada corallopsis has a widely reported distribution in the western and eastern Atlantic and some areas of the Indo-Pacific Ocean, whereas P. furcata has a more restricted distribution, reported only from Brazil and Cuba. Palisada corallopsis and P. furcata were collected from their type localities, Havana, Cuba and Ceará, Brazil, respectively, and compared by morphological and molecular analyses using rbcL and COI-5P genes. The molecular results placed the sequences from the type locality of both species in the same clade, showing low genetic divergence, 0.95 % for rbcL and 1.6 % for COI-5P. Morphologically, the species share similar habits, with branchlets bi-to trifurcated, cortical cells that may be arranged as a palisade and connected by secondary pit-connections. Our detailed morphological observations, including examination of the type specimens, and molecular analyses demonstrate that P. corallopsis and P. furcata are conspecific, P. furcata being a later taxonomic synonym of P. corallopsis.

ZMYND11 Functions in Bimodal Regulation of Latent Genes and Brain-like Splicing to Safeguard Corticogenesis.

Despite the litany of pathogenic variants linked to neurodevelopmental disorders (NDD) including autism (ASD) and intellectual disability 1,2 , our understanding of the underlying mechanisms caused by risk genes remain unclear. Here, we leveraged a human pluripotent stem cell model to uncover the neurodevelopmental consequences of mutations in ZMYND11 , a newly implicated risk gene 3,4 . ZMYND11, known for its tumor suppressor function, encodes a histone-reader that recognizes sites of transcriptional elongation and acts as a co-repressor 5,6 . Our findings reveal that ZMYND11-deficient cortical neural stem cells showed upregulation of latent developmental pathways, impairing progenitor and neuron production. In addition to its role on histones, ZMYND11 controls a brain-specific isoform switch involving the splicing regulator RBFOX2. Extending our findings to other chromatin-related ASD risk factors revealed similar developmental pathway activation and splicing dysregulation, partially rescuable through ZMYND11's regulatory functions.

Brain-derived neurotrophic factor modulation in response to oxidative stress and corticosterone: role of scopolamine and mirtazapine

Major Depressive Disorder (MDD) is a very complex disease, challenging to study and manage. The complexities of MDD require extensive research of its mechanisms to develop more effective therapeutic approaches. Crucial in the context of this disease is the role of brain-derived neurotrophic factor (BDNF) signaling pathway. AimThis manuscript aims to explore the complex relationship between MDD and BDNF signaling pathway, focusing on how BDNF is modulated in response to oxidative stress and corticosterone, known to be altered in MDD and contributing to the pathology of the disorder, when treated with scopolamine and mirtazapine. MethodsTo assess BDNF levels after the different treatment conditions, rat hippocampal slices and mice primary hippocampus and cortical cell culture were analyzed by immunofluorescence and Western blot. Key findingsBoth mirtazapine and scopolamine under stress conditions induced by hydrogen peroxide (H2O2) and corticosterone, had a significant impact on BDNF levels, and this was distinct in different neuronal models. Mirtazapine, especially when combined with H2O2, altered BDNF expression. Scopolamine when combined with both stressors also altered BDNF levels. However, its effects varied depending on the specific neuronal model and stress condition. In accordance with BDNF results, phosphorylated tropomyosin receptor kinase B (pTrkB) presented increased activation when neuronal cells subjected to stress were treated with mirtazapine or scopolamine. SignificanceCollectively, this study highlights the complex connection between these compounds, stress conditions, and BDNF/TrkB modulation, supporting the potential therapeutic effects of scopolamine and mirtazapine in modulating BDNF levels, even in stressful conditions.

α-Synuclein aggregation decreases cortico-amygdala connectivity and impairs social behavior in mice

Abnormal accumulation of insoluble α-synuclein (α-Syn) inclusions in neurons, neurites, and glial cells is the defining neuropathology of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Accumulation of α-Syn inclusions in the amygdala has been well-documented in post-mortem studies of PD and DLB brains, as well as preclinical animal models of these conditions. Though α-Syn pathology is closely associated with neurodegeneration, there is a poor correlation between neuronal loss in the amygdala and the clinical features of PD and DLB. Moreover, functional interaction between the cerebral cortex and the amygdala is critical to regulating emotion, motivation, and social behaviors. The cortico-amygdala functional interaction is likely to be disrupted by the development of α-Syn pathology in the brain. Thus, we hypothesize that neuronal α-Syn inclusions disrupt cortical modulation of the amygdala circuits and are sufficient to drive social behavioral deficits. In the present work, we designed a series of longitudinal studies to rigorously measure the time courses of neurodegeneration, functional impairment of cortico-amygdala connectivity, and development of amygdala-dependent social behavioral deficits to test this hypothesis. We injected α-Syn preformed fibrils (PFFs) into the dorsal striatum to induce α-Syn aggregation in the amygdala and the medial prefrontal cortex (mPFC) of C57BL6 mice of both sexes, followed by a detailed analysis of temporal development of α-Syn pathology, synaptic deficits, and neuronal loss in the amygdala, as well as behavioral deficits at 3–12 months post injections. Development of α-Syn inclusions caused losses of cortical axon terminals and cell death in the basolateral amygdala (BLA) at 6- and 12-months post injections, respectively. At a relatively early stage of 3 months post injections, the connection strength of the mPFC-BLA synapse was decreased in PFFs-injection mice compared to controls. Meanwhile, the PFFs-injected mice showed impaired social interaction behavior, which was rescued by chemogenetic stimulation of mPFC-BLA connections. Altogether, we presented a series of evidence to delineate circuit events in the amygdala associated with the accumulation of α-Syn inclusions in the mouse brain, highlighting that functional impairment of the amygdala is sufficient to cause social behavior deficits. The present work further suggests that early circuit modulation could be an effective approach to alleviate symptoms associated with α-Syn pathology, necessitating studies of functional consequences of α-Syn aggregation.

Sex-specific single cell-level transcriptomic signatures of Rett syndrome disease progression

Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment.

A Comparative Study of Fungal Endophytes - Endomycorrhizal Organs in Ocimum Sanctum and Santalum Album

The study of Endophytic fungi in the medicinal plants showed quite a variation. The plant Ocimum sanctum showed six types of fungi Trichoderma viridae, Fusarium solani, Gliocladium roseum, Cladosporium sp., Cladorrhinium sp. and Nigrospora sp. that were isolated from rhizosphere and found to be 42.8 % of the population of total fungi isolated, while only one type of endophyte, Mycelia sterilia was 14.2% of the total population of the isolates. The four fungi Fusarium solani, Gliocladium roseum, Mycelia sterilia and Nigrospora sp. were isolated as endophytes. with 42.8% of the total population of the isolates. In the plant Santalum album five fungi Trichoderma viridae, Stachylidium extorre, Pseudobotrytis sp., Fusarium oxysporum, Mycelia sterilia, were isolated from rhizosphere and found to be 55.55% of the population of total fungi isolated. While four fungi Chalaropsis sp., Phoma glomerata, Collectotrichum sp. and Fusarium solani were isolated as endophytes which accounted for 33.33%. The fungi common both as rhizospheric and endophytic include one isolate Collectotrichum sp. with 11.11% of the total population of the isolates. The presence of vesicles was observed within the cortical cells of both the plants Ocimum sanctum and Santalum album.

7815 Pembrolizumab-Induced Autoimmune Hypophysitis with “Isolated” ACTH Deficiency: Need for Heightened Awareness and Action Among Medical Fraternity

Abstract Disclosure: S. Shankar: None. S.S. Sundar: None. M.S. Vaishnav: None. L. Lekkala: None. K. Thummala: None. S. Srikanta: None. T. Deepak: None. R.B. Vijay: None. K. Muniraj: None. V. Nath: None. C. Siddlingappa: None. P. Ravikumar: None. M.D. Chitra: None. Introduction: Autoimmune hypophysitis caused by immune checkpoint inhibitors [ICIs; anti-CTLA-4 (Ipilimumab alone 7.9%), anti-PD-1 (Pembrolizumab alone 1.7%; nivolumab alone 0%)] are being increasingly documented, with anterior hypopituitarism affecting corticotrophs more commonly than thyrotrophs and gonadotrophs (large time span of onset; different recovery patterns). Clinical Case 2021 Sep Age 65 years (type 2 diabetes, hypertension). Renal Cell Carcinoma S/P radical nephrectomy. 2023 Jul PET-CT= Metastatic pleuropulmonary nodules. Four admissions to Specialist Oncology Hospital [Four 2 weekly cycles of Inj Pembrolizumab 200 mg (with Tab Axitinib 10 mg/day)]. After first cycle: progressive fatigue, body aches, drowsiness. S Sodium= Pre-pembrolizumab= 137 mEq/L (135-145); Post-pembrolizumab= 124, 134, 132, 124; T3= 1.63 to 0.60 to 1.24 to 1.35 ng/mL (0.97-1.69); T4= 6.83 to 4.93 to 10.44 to 11.44 mcg/dL (5.53-11); TSH= 10.46 to 6.28 to 5.39 to 9.48 mIU/mL (0.46-4.68); S Cortisol 8 am= 1.54 mcg/dL (5-25); S Potassium= 4.59 mEq/dL (3.5-5.1)]. One episode of loss of consciousness; EEG= abnormal; MRI Brain= normal. During every hospital admission, oncology, medical, endocrinology and nephrology teams attributed the same to “illness” (no specific diagnosis) and provided symptomatic treatment (IV 3% saline, tolvaptan and sodium bicarbonate tablets).2023 Nov Medicine: Very severe nausea, anorexia, generalised weakness, myalgia, hiccoughs, and inability to walk. Frustrated family members sought admission in “new” General Hospital. S Sodium= 119, 120; S Potassium= 4.8; S Creatinine= 1.67 mg/dL (0.7-1.3); S Uric acid= 4.5 mg/dL (4.40-7.60); Urine spot Sodium= 84 mmol/L; ESR= 144 mm. Endocrinology: S Cortisol 8 am= 0.09 mcg/dL;S Cortisol post 250 mcg Inj Synacthen= 3.76 (>20);Plasma ACTH= 5.4 pg/ml (9-52). S T3= 1.35; S T4= 11.44; S TSH= 9.48; LH= 3.61mIU/mL (1.5-9.3); FSH= 1.4mIU/mL (1.4-18.1); PRL= 30.1 (2.6-13.3); Testosterone total= 314 ng/dL (241-827); TPO antibodies negative. MRI-Pituitary: Partial empty sella; infundibulum neurohypophysis normal; mild asymmetric enhancement (5.5 mm) left cavernous sinus. Treatment: Tab Hydrocortisone 25 mg/day, with complete clinical and biochemical response [Suggestion of gonadotroph dysfunction and partial recovery of thyrotrope dysfunction/ injury. Hence, not on thyroxine replacement]. Clinical Lessons: Mechanisms for differential cellular vulnerability for ICI induced autoimmune pathologies [thyroid (destructive versus stimulatory), islet beta cells, adrenal cortical cells, various anterior pituitary cells (corticotrophs vs thyrotrophs and gonadotrophs] need elucidation. Specific molecular and cellular immunopathogenic pathways in different autoimmune endocrinopathies appear distinct and disparate. Presentation: 6/2/2024

6436 Adrenal Venous Congestion Clinically Mimicking Carcinoma In A Large Degenerated Adrenocortical Adenoma

Abstract Disclosure: K. Ishiwata: None. S. Suzuki: None. S. Watanabe: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None. Introduction: A large heterogenous adrenal tumor is often malignant. Only eight reported cases of adrenal adenoma harboring hemorrhage or venous thrombosis have been reported but their details not. We encountered a case of large degenerated adrenocortical adenoma harboring adrenal venous congestion mimicking adrenocortical carcinoma. Case: Adrenal tumor was incidentally detected in a 71-year-old woman with a history of hypertension, dyslipidemia, and osteoporosis in her regular health check-up. Abdominal CT and MRI demonstrated a heterogenous mass measuring 7.6 cm with peripheral enhancement in the left adrenal gland. [1]3[1]I-adosterol scintigraphy revealed accumulation only in the left tumor margins with no accumulation in [1]8F-FDG-PET scan. Results of endocrinologic evaluation were consistent with subclinical Cushing syndrome. The large size and heterogeneous nature of the mass clinically suggested adrenocortical malignancy, and left laparoscopic adrenalectomy was subsequently performed. The resected left adrenal lesion was encapsulated and measured 6.5 x 6.3 x 5.8 cm appearing almost black and partially yellow on the cut surface. Microscopically, the nodule was composed of SF-1 positive, clear cortical cells with abundant hyaline stroma containing numerous dilated veins with CD31/34-positive endothelial cells, and no foci of necrosis or hemorrhage were detected. The tumor cells above were positive for steroidogenic enzymes including CTP17, HSD3β and CYP11B1 but negative for CYP11B2. Ki-67 labeling index was <2% in the tumor. The criteria of Weiss (0 out of 9) revealed that the tumor was cortisol-producing adrenocortical adenoma. Discussion: In this case, clusters of SF1-positive cortisol producing adrenocortical adenoma cells were present in the hyalinized stroma containing many dilated blood vessels. These findings indicated that those histological features were caused by ischemic degeneration due to intratumoral circulatory disturbance, which clinically simulated adrenocortical carcinoma. Conclusion: We have experienced a very rare case of cortisol-producing adrenocortical adenoma with adrenal venous congestion, resulting in marked enlargement of the lesion. Presentation: 6/3/2024