Search bioRxiv⌕ Search

bioRxiv · 10.1101/2022.07.22.501134

Morphological evaluation of rat cerebellum following administration of nitrogen monoxide precursor and inhibitor

Abstract

In this study, the quantitative and qualitative effects of nitrogen monoxide on cerebellar histopathology, by increasing or decreasing in vivo production of this substance, were investigated. In this study, forty Wistar female rats (RAT) with a weight of about 200 to 250 grams and an average age of eight weeks were used. Rats were divided into five groups of eight, including control groups, normal saline, L-NAME, L-Arginine, L-NAME + L-Arginine. On the third, fourth and fifth days, the injection was performed intraperitoneally and on the eighteenth day, after anesthesia with ether and then craniotomy, the brain and cerebellum of the animals were removed and After quantitative measurements including weight and volume, organs were fixed in 10% formalin and after tissue preparation steps, to prepare the slide, sections with a thickness of 5 to 6 microns were prepared from the samples and by general method such as Hematoxylin-eosin and special techniques like Mason trichrome and toluidine blue were stained and evaluated. The results of this study show that in the case of cerebellum, there is no significant difference in the quantitative weight parameter between the control groups, normal saline, L-Arg, L-NAME and L-NAME + L-Arg groups. Regarding the volume parameter, a significant increase (P <0.01) was observed in L-Arg group compared to L-NAME, L-Arg + L-NAME and normal saline groups. In microscopic qualitative parameters, the most changes in the L-Arg group were seen as follows: The granular and molecular layers of the cerebellum became slightly thickened, some of the nuclei in the granular and molecular layers became severely hyperchromatized, and Purkinje cell accumulation was seen with lymphocytic invasion. In the other groups, there were no significant changes. It is inferred from this study that L-Arginine can cause histopathological changes in cerebellar tissue by increasing NO levels in cerebellum. However, in this study, unlike other similar studies, L-NAME injection did not cause significant histopathological change.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Chegini, H., Chegini, A., Gholamzad, A., Sadeghi, H., Noori Mougahi, S. M. H.. 2022-07-23. Morphological evaluation of rat cerebellum following administration of nitrogen monoxide precursor and inhibitor. https://doi.org/10.1101/2022.07.22.501134

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗