Intraperitoneal injection of lithium chloride induces lateralized activation of the insular cortex in adult mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Qian K
PROVIDER: S-EPMC8056688 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Intraperitoneal (IP) injections are an effective and reproducible route of drug administration. However, current IP equipment can be either costly, inaccurate, or unsafe for zebrafish. We describe a simple, low-cost IP setup, which can be easily assembled from inexpensive and readily available parts, and which provides a safe, reproducible, and accurate IP-injection method for experimenters.
| S-EPMC5335727 | biostudies-literature
Project description:Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-?B)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250??g/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-?B and pro-inflammatory factors, such as interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-?B-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.
| S-EPMC7081606 | biostudies-literature
Project description:Lithium compounds, a classic class of metal complex medicine that target GSK 3β and are widely known as mood-stabilizer, have recently been reported as potential anti-tumor drugs. The objective of this investigation was to explore the anticancer potential of lithium chloride (LiCl) and elucidate its mode of action in pancreatic cancer cells. The MTT, colony formation, and Edu assay were used to evaluate the impact of LiCl on pancreatic cancer cell proliferation. Various methods were employed to investigate the anti-tumor activity of LiCl and its underlying mechanisms. Cell cycle analysis and apoptosis detection assays were utilized for in vitro experiments, while the orthotopic pancreatic cancer mouse model was employed to evaluate the effectiveness of LiCl treatment in vivo. Furthermore, the impact of LiCl on the proliferation of patient-derived organoids was also studied. The results demonstrated that LiCl inhibited the proliferation of pancreatic cancer (PC) cells, induced G2/M phase arrest, and activated apoptosis. Notably, the triggering of endoplasmic reticulum (ER) stress by LiCl was observed, leading to the activation of the PERK/CHOP/GADD34 pathway, which subsequently promoted apoptosis in PC cells. In the future, Lithium compounds could become an essential adjunct in the treatment of human pancreatic cancer.
| S-EPMC10579530 | biostudies-literature
Project description:Ortholithiations of a range of arenes mediated by lithium diisopropylamide (LDA) in THF at -78 degrees C reveal substantial accelerations by as little as 0.5 mol % of LiCl (relative to LDA). Substrate dependencies suggest a specific range of reactivity within which the LiCl catalysis is optimal. Standard protocols with unpurified commercial samples of n-butyllithium to prepare LDA or commercially available LDA show marked batch-dependent rates--up to 100-fold--that could prove significant to the unwary practitioner. Other lithium salts elicit more modest accelerations. The mechanism is not discussed.
| S-EPMC2765536 | biostudies-literature
Project description:Coordinated functioning of the two cortical hemispheres is crucial for perception. The human auditory cortex (ACx) shows functional lateralization with the left hemisphere specialized for processing speech, whereas the right analyzes spectral content. In mice, virgin females demonstrate a left-hemisphere response bias to pup vocalizations that strengthens with motherhood. However, how this lateralized function is established is unclear. We developed a widefield imaging microscope to simultaneously image both hemispheres of mice to bilaterally monitor functional responses. We found that global ACx topography is symmetrical and stereotyped. In both male and virgin female mice, the secondary auditory cortex (A2) in the left hemisphere shows larger responses than right to high-frequency tones and adult vocalizations; however, only virgin female mice show a left-hemisphere bias in A2 in response to adult pain calls. These results indicate hemispheric bias with both sex-independent and -dependent aspects. Analyzing cross-hemispheric functional correlations showed that asymmetries exist in the strength of correlations between DM-AAF and A2-AAF, while other ACx areas showed smaller differences. We found that A2 showed lower cross-hemisphere correlation than other cortical areas, consistent with the lateralized functional activation of A2. Cross-hemispheric activity correlations are lower in deaf, otoferlin knockout (OTOF-/-) mice, indicating that the development of functional cross-hemispheric connections is experience dependent. Together, our results reveal that ACx is topographically symmetric at the macroscopic scale but that higher-order A2 shows sex-dependent and independent lateralized responses due to asymmetric intercortical functional connections. Moreover, our results suggest that sensory experience is required to establish functional cross-hemispheric connectivity.
| S-EPMC10372568 | biostudies-literature
Project description:Not available
2007-07-20 | PRD000770 | Pride
Project description:An effective and pain-free killing method is required to achieve the goal of euthanasia, a "good death". Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique in laboratory rats, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control. Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 84) were block randomised by sex and strain to receive one of three treatments: 1) 800 mg/kg PB (pH 11), 2) saline or 3) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale (RGS), writhing, back arching) was evaluated at baseline, before loss of righting reflex (LORR, PB group), and at 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups). In the PB group, mean time to LORR was 78 ± 7.9 seconds. In the vehicle control groups, RGS scores were increased at 151s PI (SD: p = 0.0002, 95%CI 0.73 to 0.20) from baseline, as was relative frequency of writhing (SD: p < 0.0001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0005, 95%CI 0.71 to 0.18; Wistar: p = 0.0234, 95%CI 0.91 to 0.07) but the relative frequency of writhing did not (p > 0.999). The RGS scores and the relative frequency of writhing remained low in the PB and saline groups (p > 0.05). These results show that, vehicle controls for IP PB result in signs associated with pain, pain may not be experienced following IP PB when LORR occurs quickly, and that the effects of PB limit behavioral pain assessments.
| S-EPMC7470368 | biostudies-literature
Project description:Epithelial‑to‑mesenchymal transition (EMT) confers stem cell‑like phenotype and more motile properties to carcinoma cells. During EMT, the expression of E‑cadherin decreases, resulting in loss of cell‑cell adhesion and increased migration. Expression of Twist1 and other pleiotropic transcription factors, such as Snail, is known to activate EMT. We established primary colon cancer cell cultures from samples of operated patients and validated cultures by cytogenetic and molecular biology approaches. Western blot assay, quantitative real‑time PCR and immunofluorescence were performed to investigate the expression of E‑cadherin, vimentin, β‑catenin, cytokeratin‑20 and ‑18, Twist1, Snail, CD44, cyclooxygenase‑2 (COX2), Sox2, Oct4 and Nanog. Moreover, cell differentiation was induced by incubation with LiCl‑containing medium for 10 days. We observed that these primary colorectal cancer (CRC) cells lost expression of the E‑cadherin epithelial marker, which was instead expressed in cancer and normal colon mucosa of the same patient, while overexpressed vimentin (mesenchymal marker), Twist1, Snail (EMT markers) and COX2. Cytokeratin‑18 was expressed both in tissues and cell cultures. Expression of stem cell markers, such as CD44, Oct4 and Nanog, were also observed. Following differentiation with the glycogen synthase kinase 3β (GSK3β) inhibitor LiCl, the cells began to express E‑cadherin and, at once, Twist1 and Snail expression was strongly downregulated, suggesting a MET‑reverting process. In conclusion, we established primary colon mesenchymal cancer cell cultures expressing mesenchymal and epithelial biomarkers together with high level of EMT transcription factors. We propose that they could represent a good model for studying EMT and its reverting mechanism, the mesenchymal‑to‑epithelial transition (MET). Our observation indicates that LiCl, a GSK3β inhibitor, induces MET in vitro, suggesting that LiCl and GSK3β could represent, respectively, interesting drug, and target for CRC therapy.
| S-EPMC4383027 | biostudies-literature
Project description:To determine if methamphetamine-dependent (MD) individuals exhibit behavioral or neural processing differences in risk-taking relative to healthy comparison participants (CTL).This was a cross-sectional study comparing two groups' behavior on a risk-taking task and neural processing as assessed using functional magnetic resonance imaging (fMRI).The study was conducted in an in-patient treatment center and a research fMRI facility in the United States.Sixty-eight recently abstinent MD individuals recruited from a treatment program and 40 CTL recruited from the community completed the study.The study assessed risk-taking behavior (overall and post-loss) using the Risky Gains Task (RGT), sensation-seeking, impulsivity and blood-oxygenation-level-dependent activation in the brain during the decision phase of the RGT.Relative to CTL, MD displayed decreased activation in the bilateral rostral anterior cingulate cortex (ACC) and greater activation in the left insula across risky and safe decisions (P?<?0.05). Right mid-insula activation among CTL did not vary between risky and safe decisions, but among MD it was higher during risky relative to safe decisions (P?<?0.05). Among MD, lower activation in the right rostral ACC (r?=?-0.39, P?<?0.01) and higher activation in the right mid-insula (r?=?0.35, P?<?0.01) during risky decisions were linked to a higher likelihood of choosing a risky option following a loss.Methamphetamine-dependent individuals show disrupted risk-related processing in both anterior cingulate and insula, brain areas that have been implicated in cognitive control and interoceptive processing. Attenuated neural processing of risky options may lead to risk-taking despite experiencing negative consequences.
| S-EPMC3947108 | biostudies-literature
Project description:Touch is a fundamental, but complex, element of everyday interaction that impacts one's sensory and affective experience via interoceptive processing. The insular cortex is an integral component of the neural processes involved in interoception, i.e. the generation of an "emotional moment in time" through the sensing of the internal body state (Craig, A.D., 2002. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci 3, 655-666.). Here, we examine the contribution of different parts of the insular cortex in the representation of both affective and sensory aspects of touch. To that end, subjects were administered a cued application of touch during functional MRI. We find that stimulus-related activation occurs in the mid-to-posterior insula, whereas anticipatory related activation is seen mostly in anterior insula. Moreover, the degree of activation in anterior insula during anticipation is correlated with the degree of activation in the posterior insula and caudate during stimulus processing. Finally, the degree of activation in the anterior insula during anticipation is also correlated with experienced intensity of the touch. Taken together, these results are consistent with the hypothesis that the anterior insula is preparing for the sensory and affective impact of touch. This preparatory function has important implications for the understanding of both anxiety and addictive disorders because dysfunctions in anticipatory processing are a fundamental part of the psychopathology.
| S-EPMC3758834 | biostudies-literature