Number Of Neuronal Cells Research Articles

Loss of function in Drosophila transcription factor Dif delays brain development in larvae resulting in aging adult brain

Drosophila NF-κB transcription factor Dif has been well known for its function in innate immunity, and recent study also reveals its role in neuronal cells. However, the underlying mechanisms of Dif in the brain remain elusive. In this study, we aim to investigate the function of Dif in Drosophila brain development and how Dif regulates structure and plasticity of the brain to affect aging and behaviors. Based on the analysis of differentially expressed genes, we identified key genes associated with cell division, development and aging in the brain of Dif1 loss of function mutant. In Dif1 larvae, we found that the metamorphosis and brain development were delayed, and cell division was decreased. In Dif1 adults, the number of neuron cells was reduced in the brain, the lifespan and locomotor activity were decreased, protein markers associated with aging-related neurodegenerative diseases in the brain were altered in abundance or activity. Our results indicated that Dif plays a crucial role in brain plasticity and neurogenesis, dysfunction of Dif delays larval brain development and impacts proliferation of neuronal cells, resulting in aging adult brain by regulating expression of key genes in multiple signaling pathways involved in cell division, neurogenesis and aging.

Heat-Processed Soybean Germ Extract and Lactobacillus gasseri NK109 Supplementation Reduce LPS-Induced Cognitive Impairment and Colitis in Mice.

Soybean alleviates cognitive impairment. In our preparatory experiment, we found that dry-heat (90 °C for 30 min)-processed soybean embryo ethanol extract (hSE) most potently suppressed lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in BV2 cells among dry-heat-, steaming-, and oil exclusion-processed soybean embryo ethanol extracts (SEs). Heat processing increased the absorbable soyasaponin Bb content of SE. Therefore, we investigated whether hSE and its supplement could mitigate LPS-impaired cognitive function in mice. Among dry-heat-, steaming-, and oil exclusion-processed SEs, hSE mitigated LPS-impaired cognitive function more than parental SE. hSE potently upregulated LPS-suppressed brain-derived neurotropic factor (BDNF) expression in the hippocampus, while LPS-induced TNF-α and IL-1β expression in the hippocampus and colon were downregulated. Lactobacillus gasseri NK109 additively increased the cognitive function-enhancing activity of hSE in mice with LPS-induced cognitive impairment as follows: the hSE and NK109 mix potently increased cognitive function and hippocampal BDNF expression and BDNF-positive neuron cell numbers and decreased TNF-α expression and NF-κB-positive cell numbers in the hippocampus and colon. These findings suggest that hSE and its supplement may decrease colitis and neuroinflammation by suppressing NF-κB activation and inducing BDNF expression, resulting in the attenuation of cognitive impairment.

Lutein Extended Astrocyte Networks and Increased the Number of Retinal Neuronal Cells in Neonatal Rats With Retinopathy of Prematurity

Lutein Extended Astrocyte Networks and Increased the Number of Retinal Neuronal Cells in Neonatal Rats With Retinopathy of Prematurity

Effects of Evodiamine on Behavior and Hippocampal Neurons through Inhibition of Angiotensin-Converting Enzyme and Modulation of the Renin Angiotensin Pathway in a Mouse Model of Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or other catastrophic incidents, typically characterized by heightened anxiety, depressive symptoms, and cognitive dysfunction. In this study, animals subjected to single prolonged stress (SPS) were administered evodiamine (EVO) and compared to a positive control group receiving sertraline. The animals were then assessed for alterations in anxiety, depression, and cognitive function. Histological analysis was conducted to examine neuronal changes in the hippocampus. In order to predict the core targets and related mechanisms of evodiamine intervention in PTSD, network pharmacology was used. The metabolic markers pre- and post-drug administration were identified using nontargeted serum metabolomics techniques, and the intersecting Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened. Finally, the core targets were validated through molecular docking, enzyme-linked immunosorbent assays, and immunofluorescence staining to confirm the anti-PTSD effects and mechanisms of these targets. As well as improving cognitive impairment, evodiamine reversed anxiety- and depression-like behaviors. It also inhibited the reduction in the number of hippocampal neuronal cells and Nissl bodies in SPS mice inhibited angiotensin converting enzyme (ACE) levels in the hippocampus of SPS mice, and modulated the renin angiotensin pathway and its associated serum metabolites in brain tissue. Evodiamine shows promise as a potential candidate for alleviating the symptoms of post-traumatic stress disorder.

Evaluation of beneficial effects of dexpanthenol on hypoxic-ischemic encephalopathy

ABSTRACT Hypoxic-ischemic encephalopathy (HIE) is a cause of serious morbidity and mortality in newborns. Dexpanthenol, which is metabolized into D-pantothenic acid, has antioxidant and other potentially therapeutic properties. We examined some effects of dexpanthenol on the brains of week-old rat pups with HIE induced by obstruction of the right carotid artery followed by keeping in 8% O2 for 2 hours. Dexpanthenol (500 mg/kg) was administered intraperitoneally to 16 of 32 pups with HIE. Protein, DNA, and lipid oxidation degradation products were assayed and hippocampal and cortical cell apoptosis and neuronal cell numbers were evaluated in stained sections. Dexpanthenol application reduced oxidative stress and inflammation. TNF-α and IL-6 cytokine levels in HIE also decreased with dexpanthenol treatment. The numbers of caspase-3 positive cells in the dentate gyrus and CA1/CA2/CA3 regions of the hippocampus was lower, and apoptosis was decreased in the dexpanthenol-treated animals. These findings suggest possible clinical applications of dexpanthenol in human HIE.

Electroacupuncture Ameliorates Cerebral Ischemia-reperfusion Injury by Inhibiting Pyroptosis through the Sirtuin-1 Pathway

Abstract Objective: NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis is pivotal in the pathological development of cerebral ischemia/reperfusion injury (CIRI). Although previous research has shown that electroacupuncture (EA) can alleviate CIRI through sirtuin-1 (SIRT1), the mechanism has not been well elucidated. Our study aimed to clarify whether the neuroprotective functions of EA are related to the reduction in NLRP3-mediated pyroptosis through the SIRT1 pathway. Materials and Methods: Rats received daily pretreatment with EA for 5 consecutive days before undergoing middle cerebral artery occlusion surgery. The Longa score was used to assess neurologic function. Infarct volume and morphological alterations were analyzed using 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. In addition, neuronal pyroptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling/caspase-1 and neuronal nuclear antigen/caspase-1 immunofluorescence double staining. Levels of expression of pyroptosis markers were assessed by Western blotting and enzyme-linked immunosorbent assay. Results: EA improved deficits in neurologic function and minimized cerebral infarct volume. Mechanistically, a number of neuronal pyroptotic cells and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, and gasdermin D in the cerebral cortex were markedly reduced by EA treatment, and conversely, SIRT1 levels were increased. Notably, the specific SIRT1 inhibitor, EX527, reversed the effects of EA. Conclusions: EA potentially exerts a neuroprotective effect against CIRI through the SIRT1 pathway in NLRP3-mediated pyroptosis.

Morphological heterogeneity of neurons in the human central amygdaloid nucleus.

The central amygdaloid nucleus (CeA) has an ancient phylogenetic development and functions relevant for animal survival. Local cells receive intrinsic amygdaloidal information that codes emotional stimuli of fear, integrate them, and send cortical and subcortical output projections that prompt rapid visceral and social behavior responses. We aimed to describe the morphology of the neurons that compose the human CeA (N = 8 adult men). Cells within CeA coronal borders were identified using the thionine staining and were further analyzed using the "single-section" Golgi method followed by open-source software procedures for two-dimensional and three-dimensional image reconstructions. Our results evidenced varied neuronal cell body features, number and thickness of primary shafts, dendritic branching patterns, and density and shape of dendritic spines. Based on these criteria, we propose the existence of 12 morphologically different spiny neurons in the human CeA and discuss the variability in the dendritic architecture within cellular types, including likely interneurons. Some dendritic shafts were long and straight, displayed few collaterals, and had planar radiation within the coronal neuropil volume. Most of the sampled neurons showed a few to moderate density of small stubby/wide spines. Long spines(thin and mushroom) were observed occasionally. These novel data address the synaptic processing and plasticity in the human CeA. Our morphological description can be combined with further transcriptomic, immunohistochemical, and electrophysiological/connectional approaches.It serves also to investigate how neurons are altered in neurological and psychiatric disorders with hindered emotional perception, in anxiety, following atrophy in schizophrenia, and along different stages of Alzheimer's disease.

AIF translocation into nucleus caused by Aifm1 R450Q mutation: generation and characterization of a mouse model for AUNX1.

Mutations in AIFM1, encoding for apoptosis-inducing factor (AIF), cause AUNX1, an X-linked neurologic disorder with late-onset auditory neuropathy (AN) and peripheral neuropathy. Despite significant research on AIF, there are limited animal models with the disrupted AIFM1 representing the corresponding phenotype of human AUNX1, characterized by late-onset hearing loss and impaired auditory pathways. Here, we generated an Aifm1 p.R450Q knock-in mouse model (KI) based on the human AIFM1 p.R451Q mutation. Hemizygote KI male mice exhibited progressive hearing loss from P30 onward, with greater severity at P60 and stabilization until P210. Additionally, muscle atrophy was observed at P210. These phenotypic changes were accompanied by a gradual reduction in the number of spiral ganglion neuron cells (SGNs) at P30 and ribbons at P60, which coincided with the translocation of AIF into the nucleus starting from P21 and P30, respectively. The SGNs of KI mice at P210 displayed loss of cytomembrane integrity, abnormal nuclear morphology, and dendritic and axonal demyelination. Furthermore, the inner hair cells and myelin sheath displayed abnormal mitochondrial morphology, while fibroblasts from KI mice showed impaired mitochondrial function. In conclusion, we successfully generated a mouse model recapitulating AUNX1. Our findings indicate that disruption of Aifm1 induced the nuclear translocation of AIF, resulting in the impairment in the auditory pathway.

(275) IGFBP5 Short Hairpin RNA (shRNA) Constructs Improve Erectile Function in a Mouse Model of Cavernous Nerve Injury

Abstract Introduction Radical prostatectomy for prostate cancer not only induces cavernous nerve injury but also causes cavernous angiopathy, which is responsible for poor responsiveness to phosphodiesterase-5 inhibitors. Insulin-like growth factor-binding protein 5 (IGFBP5) promotes cell death and induces apoptosis in various cell types. Objective To investigate the effectiveness of IGFBP5 knockdown at improving erectile function in a mouse model of cavernous nerve injury. Methods Eight-week-old C57BL/6 mice were used to prepare cavernous nerve injury model. Mice were divided into 4 groups: a sham operation group and three cavernous nerve injury (CNI) groups, which were administered intracavernous injections of phosphate buffered saline, scrambled control shRNA, or shRNA targeting mouse IGFBP5 (shIGFBP5) lentivirus particles. One week later, we measured erectile function by electrically stimulating the bilateral cavernous nerve. Results IGFBP5 expression in cavernous tissues were significantly increased in CNI mice compare to sham mice. CNI mice had reduced erectile function, but shIGFBP5 treatment resulted in significant improvements. Furthermore, in CNI mice, numbers of cavernous endothelial cells, pericytes, and neuronal cells were increased by shIGFBP5 treatment. Conclusions Knockdown of IGFBP5 improved erectile function in CNI mice by enhancing neurovascular regeneration. Local inhibition of IGFBP5 expression may provide a new treatment strategy for the treatment of neurovascular diseases. Disclosure No.

Attenuation of propofol-induced hippocampal neuron damage in developing rats by dexmedetomidine

This study explored the mechanism of dexmedetomidine attenuating propofol damage to hippocampal neurons in rats. By constructing rat hippocampal neuron model and carrying out targeted intervention; enzyme linked immunosorbent assay (ELISA) detected IL-1β and IL-18 levels; while Nissl staining observed hippocampus Histopathology; flow cytometry quantitatively analyzed the number of hippocampal neuron cells and apoptosis rate. Moreover, levels of PKA, Caspase-1 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) and corresponding proteins were measured. Results showed that, there were more Nissl bodies in cytoplasm of hippocampal neurons in control group, and distribution in the cytoplasm was relatively uniform. Moreover, IL-1β and IL-18 in model group continued to increase; while dexmedetomidine effectively inhibited apoptosis of hippocampal neurons, which may be related to decreased expression of protein kinase A (PKA). After using PKA inhibitors, apoptosis was significantly inhibited, and when the expression of PKA was reduced, Caspase-1 was down-regulated along with reduced NLRP3 level, which improved the injury of hippocampal neurons. Dexmedetomidine can therefore down-regulate the level of Caspase-1 in hippocampal neurons by inhibiting the PKA signaling pathway, improving apoptosis, reducing the genetic and protein expressions of NLRP3, and slowing down the damage of hippocampal neurons.

Sepsis-associated encephalopathy: Autophagy and miRNAs regulate microglial activation.

Sepsis-associated encephalopathy (SAE) describes diffuse or multifocal cerebral dysfunction caused by the systemic inflammatory response to sepsis. SAE is a common neurological complication in patients in the middle and late stages of sepsis in the intensive care unit. Microglia, resident macrophages of the central nervous system, phagocytose small numbers of neuronal cells and apoptotic cells, among other cells, to maintain the dynamic balance of the brain's internal environment. The neuroinflammatory response induced by activated microglia plays a central role in the pathogenesis of various central nervous system diseases. In this paper, we systematically describe the functions and phenotypes of microglia, summarize how microglia mediate neuroinflammation and contribute to the occurrence and development of SAE, and discuss recent progress in autophagy- and microRNA-mediated regulation of microglial activation to provide a theoretical basis for the prevention and treatment of SAE and identify related therapeutic targets.

Abstract TP300: Apolipoprotein-E Deficiency and High Fat Diet Alter Immunomodulatory Cellular and Molecular Determinants Promoting Atherosclerosis, a Stroke Risk Factor

Background: Most ischemic strokes are caused by atherosclerosis. Atherosclerotic plaque formation is modulated by genetic and environmental interactions. Apolipoprotein E (ApoE) regulates lipid metabolism, and its deficiency is associated with dyslipidemia and atherosclerosis. ApoE is abundantly expressed in glial cells and neurons of the brain, affecting the blood brain barrier and cognitive function. Poor dietary habits promote the onset of atherosclerosis. In this study, we examined the effects of ApoE deficiency and high fat diet (HFD) on plaque formation and immunomodulatory cellular and molecular mechanisms in mice models. Methods: Wild type and ApoE knockout (KO) mice were fed with normal or HFD. Carotid plaques were examined using hematoxylin and eosin staining. Targeted proteomic profiling identified the circulating inflammatory proteins. Pathway specific transcriptomic profiles were identified using PCR arrays and real-time PCR. Immunohistochemistry assays were done in brain sections using a neuronal marker (NeuN), an astrocyte marker (GFAP) and a microglia marker (Iba1). The expression of Pentraxin-3 (PTX3), lipocalin2, and PAI-1 were examined using immunohistochemistry. Images were acquired and analyzed using a Keyence fluorescence microscope and NIH ImageJ. Results: ApoE deficiency and HFD enhanced atherosclerotic plaque formation as a function of age in association with a significant increase in circulating pro-inflammatory cytokines in blood/plasma, including M-CSF, C-reactive protein, and PTX3. The number of microglial cells and astrocytes was increased with altered morphology in ApoE KO and aged animals’ brain cortex and dentate gyrus. Whereas neuronal cell number was decreased in the brains of ApoE deficient and aged mice. The mRNA levels of SELE, PAI-1, lipocalin2, and PTX3 were upregulated in ApoE deficient and WT animals fed with HFD. Higher levels of PTX3 were also observed in atherosclerotic plaques. Conclusion: ApoE deficiency and HFD may play a key role in altering immunomodulatory cellular responses and initiating pro-inflammatory molecular signaling. These events may promote atherosclerotic plaque formation, a risk factor for ischemic stroke and worsen brain damage.

Microglial Phagocytosis During Embryonic and Postnatal Development.

Microglia play decisive roles during the development of the central nervous system (CNS). Phagocytosis is one of the classical functions attributed to microglia, being involved in nearly all phases of the embryonic and postnatal development of the brain, such as rapid clearance of cell debris to avoid an inflammatory response, controlling the number of neuronal and glial cells or their precursors, contribution to axon guidance and to refinement of synaptic connections. To carry out all these tasks, microglial cells are equipped with a panoply of receptors, that convert microglia to the "professional phagocytes" of the nervous parenchyma. These receptors are modulated by spatiotemporal cues that adapt the properties of microglia to the needs of the developing CNS. Thus, in this chapter, we will discuss the role of microglial phagocytosis in all the aforementioned processes. First, we will explain the general phagocytic process, to describe afterward the performance of microglial cells in detail.

Neuropathological insights from SHANK3 mutant animal models

SHANK3 is a protein primarily found in the postsynaptic density (PSD) of excitatory synapses in the brain. Heterozygous mutations in the shank3 gene have been linked to autism spectrum disorder (ASD) and intellectual disability. There are various animal models carrying mutant SHANK3 that have provided valuable insights into the pathogenesis of ASD. In this review, we will discuss these animal models, with a specific focus on the neuropathology observed in shank3 mouse and monkey models. These models are particularly important as they share closer similarities to humans and are capable of more accurately recapitulating the neuropathological features observed in individuals with ASD. Mice with mutations in the shank3 gene exhibit deficits in social behavior, communication, and repetitive behaviors, which are core features of ASD and support the link between SHANK3 and ASD. However, studies of monkey models with SHANK3 targeting by CRISPR/Cas9 have demonstrated that, unlike mice with completely knocked-out shank3 genes, the monkey model with complete deletion of SHANK3 displays a reduction in the number of neuronal cells. This review discusses the species-specific neuropathology in SHANK3/shank3 knockout mice and monkeys. The differences in neuropathology in SHANK3/shank3 mutant mouse and monkey models suggest that non-human primate models are highly valuable for investigating the mechanism of neurodegeneration that may selectively occur in primate brains.

LPS-Induced Neuron Cell Apoptosis through TNF-α and Cytochrome c Expression in Dental Pulp.

Inflammation of the dental pulp tissue caused by bacteria, creating an immunology response of death of the dental pulp, is called apoptosis. The Porphyromonas gingivalis that cause apoptosis is lipopolysaccharide (LPS) through toll-like receptor (TLR) via two different mechanisms, intracellular and extracellular pathways. This study analyzed the role of LPS exposure of neuron cells, tumor necrosis factor-α (TNF-α), and cytochrome c (cyt-c) expression in the dental pulp to predict the possible mechanism of apoptosis. The lower tooth of Sprague Dawley rats was opened and exposed to LPS for 48 hours. Then the neuron cell analyzed histopathology using hematoxylin-eosin, whereas the TNF-α and cyt-c expression with indirect immunohistochemistry using a light microscope. The relationship between neuron cells with TNF-α and cyt-c was analyzed using stepwise regression linear analysis. The LPS exposure showed a lower number of neuron cells and had a relationship with TNF-α expression but not with cyt-c, while compared with control, both TNF-α and cyt-c expression were higher in neuron cells. LPS exposure in dental pulp is possible to stimulate the apoptosis process through extracellular pathways marked by higher TNF-α expression.

Arsenic induced neurotoxicity in the brain of ducks: The potential involvement of the gut-brain axis

BackgroundArsenic is a widely distributed ecotoxic pollutant that has been found to cause neurotoxicity in a variety of species. Gut-brain axis is a two-way information network between the gut microbiome and the brain, which is closely related to organismal health. However, the role of the gut-brain axis in arsenic-induced neurotoxicity remains largely unknown. MethodsIn order to explore whether there is a relationship between brain and gut microbiota of meat ducks, we performed molecular biological detection including RT-qPCR and Western blot, as well as morphological detection including, HE staining and immunohistochemistry. Meanwhile, intestinal contents were analyzed using 16 S ribosomal RNA gene sequencing and analysis ResultsIn this study, we investigated whether arsenic trioxide (ATO) can activate the gut microbiome-brain axis to induce intestinal and brain injury. The results showed that ATO-exposure disrupted the diversity balance of intestinal microbiota and integrity and injured the intestinal structure. ATO-exposure also reduced the number of glycogen and goblet cells in the duodenum. In addition, exposure to ATO caused intestinal inflammatory injury by activating NF-κB signaling pathway and promoting the expression of its target genes. Meanwhile, the tight junction-related proteins (ZO-1, occludin) of gut and brain were reduced by ATO exposure. Furthermore, results also revealed that ATO-exposure induced brain injury, including neuronal cell vacuolization and reduced numbers of neuronal cells in the cortex and hippocampus. Remarkably, ATO-exposure also disrupted neurotransmitter levels. Additionally, our further molecular mechanism study revealed that ATO-exposure increased the expression of autophagy and apoptosis related mRNA and proteins levels in the brain tissues. ConclusionAltogether, these findings provide a new insight into that ATO-exposure induced intestinal injury and aggravated neurotoxicity via the gut-brain axis.

ANDA: an open-source tool for automated image analysis of in vitro neuronal cells

BackgroundImaging of in vitro neuronal differentiation and measurements of cell morphologies have led to novel insights into neuronal development. Live-cell imaging techniques and large datasets of images have increased the demand for automated pipelines for quantitative analysis of neuronal morphological metrics.ResultsANDA is an analysis workflow that quantifies various aspects of neuronal morphology from high-throughput live-cell imaging screens of in vitro neuronal cell types. This tool automates the analysis of neuronal cell numbers, neurite lengths and neurite attachment points. We used chicken, rat, mouse, and human in vitro models for neuronal differentiation and have demonstrated the accuracy, versatility, and efficiency of the tool.ConclusionsANDA is an open-source tool that is easy to use and capable of automated processing from time-course measurements of neuronal cells. The strength of this pipeline is the capability to analyse high-throughput imaging screens.

In vivo study of the utility of selective intra-arterial injection of thiopental for neuroprotection in reversible cerebral ischemia.

Neuroprotective agents are needed to reduce cerebral damage during surgical or neurointerventional procedures including stroke patients. To evaluate if thiopental can be used as a neuroprotective agent when injected intra-arterially in a transient ischemia model. In total, 24 rabbits were studied as four groups of six animals. Group 1 served as the control group. In group 2, transient ischemia was obtained by intracarotid administration of degradable starch microspheres (DSM). Group 3 was administered thiopental intra-arterially via the carotid artery. Group 4 (experimental group) received both thiopental and DSM intra-arterially. DSM and thiopental were administered through a microcatheter placed into the common carotid artery via the central ear artery access. After sacrifice, apoptotic cells in the cerebral tissues of the animals were evaluated in H&E and TUNEL stained slides. There was a significant increase in the number of apoptotic glial or neuronal cells in group 2 compared to the control group and group 3. The mean number of both the apoptotic neuronal cells (6.8 ± 2.1 vs. 2.5 ± 1.3, P < 0.001) and the apoptotic glial cells (9.4 ± 3.1 vs. 4.6 ± 1.6, P < 0.001) were higher in group 2 compared to group 4. In addition, a higher level of neurological improvement was observed in group 4 compared to group 2 based on neurological assessment score. The intra-arterial administration of thiopental has a protective effect on both glial and neuronal cells during temporary cerebral ischemia in low doses.

Long Noncoding RNA MIAT Modulates Chronic Retinal Ischemia-Reperfusion Injury in Mice via the microRNA-203-3p/SNAI2 Axis.

Retinal ischemia-reperfusion injury (RIRI) is a vital pathological process of multiple ocular diseases. This study aimed at investigating the effects of the MIAT/miR-203-3p/SNAI2 axis on RIRI. RIRI was produced by inducing an exceedingly high intraocular pressure (IOP) in mice. Mouse retinal ganglion cells (RGCs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic in vitro models. Relevant oligonucleotides or plasmids were transfected into OGD/R-induced RGCs in vitro or injected into RIRI mice models in vivo via a vitreous cavity. The findings of our paper indicated that MIAT and SNAI2 were highly expressed and miR-203-3p was lowly expressed in mouse RIRI tissues and OGD/R-induced RGCs. Interfering MIAT promoted the viability of OGD/R-induced RGCs, decreased apoptosis, and reduced oxidative stress in vitro. Silencing MIAT increased retinal neuronal cell numbers and decreased retinal neuronal cell apoptosis in mouse RIRI tissues in vivo. MIAT sponged miR-203-3p, and miR-203-3p targeted and inhibited SNAI2 expression. SNAI2 up-regulation or miR-203-3p down-regulation reversed the protective effects of MIAT down-regulation on RIRI in mice and OGD/R-induced RGCs. MIAT sponges miR-203-3p upregulated the expression of SNAI2, thereby promoting RIRI in mice. In summary, MIAT may be a therapeutic target for the treatment of chronic RIRI.

Hallucinogenic activity, neurotransmitters release, anxiolytic and neurotoxic effects in Rat's brain following repeated administration of novel psychoactive compound 25B-NBOMe

2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)etanoamine (25B-NBOMe) is a highly selective 5-HT2A receptor agonist, exhibiting a potent hallucinogenic activity. In the present study, we investigated the effect of a 7-day treatment with 25B-NBOMe in a dose of 0.3 mg/kg on the following: the neurotransmitter release in vivo using microdialysis in freely moving animals, hallucinogenic activity measured in the Wet Dog Shake (WDS) test, anxiety level as measured in the light/dark box (LDB) and locomotor activity in the open field (OF) test, DNA damage with the comet assay, and on a number of neuronal and glial cells with immunohistochemistry. Repeated administration of 25B-NBOMe decreased the response to a challenge dose (0.3 mg/kg) on DA, 5-HT and glutamatergic neurons in the rats’ frontal cortex, striatum, and nucleus accumbens. The WDS response dropped drastically after the second day of treatment, suggesting a rapid development of tolerance. LDB and OF tests showed that the effect of 25B-NBOMe on anxiety depends on the treatment and environmental settings. Results obtained with the comet assay indicate a genotoxic properties in the frontal cortex and hippocampus. An increase in immunopositive glial but not neuronal cells was observed in the cortical regions but not in the hippocampus. In conclusion, our study showed that a chronic administration of 25B-NBOMe produces the development of tolerance observed in the neurotransmitters release and hallucinogenic activity. The oxidative damage of cortical and hippocampal DNA implies the generation of free radicals by the drug, resulting in genotoxicity but rather not in neurotoxic tissue damage. Behavioral tests show that 25B-NBOMe exerts anxiogenic effect after single and repeated treatment.