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Transcriptome analysis of the hippocampus in late postnatal mice after repeated ketamine anesthesia

ABSTRACT: Numerous recent studies showed that early anesthesia during neurodevelopment may induce changes in specific behaviors. We further studied the effects of early anesthetic exposures regarding addiction behavior later in life. Postnatal day (PND) 16 C57BL/6 mice received ketamine anesthesia for 5 consecutive days. Addiction behavior was evaluated 1 week after anesthesia treatment. Neurological changes after repeated anesthesia were evaluated using high-performance liquid chromatography, RNA sequencing, electrophysiology studies. Repeated ketamine anesthesia during the critical neurodevelopment period increased the expression of genes involved with action potential, and induced excitatory/inhibitory (E/I) imbalance in hippocampal CA1 pyramidal neurons of male mice. Such neurological changes were associated with increases in drug-induced contextual addiction memory.

ORGANISM(S): Mus musculus

PROVIDER: GSE175894 | GEO | 2022/07/14

REPOSITORIES: GEO

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Transcriptomic Response of Brain Tissue to Focused Ultrasound-Mediated Blood-Brain Barrier Disruption Depends Strongly on Anesthesia - Bulk RNA-seq

Project description:Focused ultrasound (FUS) mediated blood brain barrier disruption (BBBD) is a promising strategy for the targeted delivery of systemically-administered therapeutics to the central nervous system (CNS). Pre-clinical investigations of BBBD have been performed on different anesthetic backgrounds; however, the potential influence of the choice of anesthetic on the molecular response to BBBD is unknown, despite its potential to critically affect interpretation of experimental therapeutic outcomes. Here, using bulk RNA sequencing approaches, we comprehensively examined the transcriptomic response of both normal brain tissue and brain tissue exposed to FUS-induced BBBD in mice anesthetized with either Isoflurane with medical air (Iso) or Ketamine/Dexmedetomidine (KD). In normal murine brain tissue, Iso alone elicited minimal differential gene expression (DGE) and repressed pathways associated with neuronal signaling. KD alone, however, led to massive DGE and enrichment of pathways associated with protein synthesis. In brain tissue exposed to BBBD (1 MHz, 0.5 Hz pulse repetition frequency, 0.4 MPa peak-negative pressure), we systematically evaluated the relative effects of anesthesia, microbubbles, and FUS on the transcriptome. Of particular interest, we observed that gene sets associated with sterile inflammatory responses and cell-cell junctional activity were induced by BBBD, regardless of the choice of anesthesia. Meanwhile, gene sets associated with metabolism, platelet activity, tissue repair, and signaling pathways, were differentially affected by BBBD, with a strong dependence on the anesthetic. We conclude that the underlying transcriptomic response to FUS-mediated BBBD may be powerfully influenced by anesthesia. These findings raise considerations for the translation of FUS-BBBD delivery approaches that impact, in particular, metabolism, tissue repair, and intracellular signaling.

2020-06-11 | GSE152171 | GEO

Project description:Although sevoflurane is one of the most commonly used inhalational anesthetic agent, the popularity of desflurane is increasing to a similar level. The main beneficial property of desflurane is the relatively fast emergence of the patient from the anesthetic state after halting its supply compared with anesthesia using other anesthetic agents. However, there has been no comprehensive comparison of the effects of these two anesthetic agents on alterations in liver gene expression profiles in animals, including humans, to assess the kinds of biological abnormalities/changes and their levels in the host. Thus, we compared alterations in the global gene expression profiles in the livers of rats subjected to inhalational anesthesia by sevoflurane or desflurane by a next-generation sequencing method.

2024-02-21 | GSE244436 | GEO

Transcriptome analysis of the hippocampus in late postnatal mice after repeated ketamine anesthesia

Project description:Transcriptome analysis of the hippocampus in late postnatal mice after repeated ketamine anesthesia

| PRJNA734265 | ENA

Astrocytes modulate a specific paraventricular thalamus-prefrontal cortex projection to enhance consciousness recovery from sevoflurane anesthesia in mice

Project description:Previous studies have proved that astrocytes may be a key neural substrate that regulates wakefulness and consciousness recovery from general anesthesia, while the exact molecular target in astrocytes is still unclear. Using virus injection and in vivo fiber photometry in mice, we found both activating astrocytes and knocking down astrocytic Kir4.1 in paraventricular thalamus (PVT) promotes the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVTGRM and PVTChAT neurons. Patch-clamp recording results proved that Astrocytic Kir4.1-mediated modulation of sevoflurane on PVT mainly works on PVTChAT neurons. Moreover, we found that PVTChAT neurons project mainly to the mPFC. This specific paraventricular thalamus to prefrontal cortex projection is involved in recovery of consciousness from sevoflurane anesthesia indirectly through modulation of astrocytes. In summary, our findings support the novel conception that the volatile anesthetic sevoflurane can inhibit PVT astrocytic Kir 4.1 to maintain and/or increase neuronal firing of PVTChAT neurons, which mainly projects to mPFC and promotes consciousness recovery from anesthesia.

2024-07-20 | GSE240388 | GEO

Transcription profiling of rat amygdala following anesthesia with isoflurane, pain or following fear conditioning in the presence and absence of isofluran

Project description:Fear conditioning in rats leads to long term memory (LTM) formation. A central neural substrate for LTM is the basolateral amygdala. We sought the expression changes specific to LTM at 6h following anesthesia with isoflurane (a general anesthetic and an effective amnestic agent), following pain (a component of conditioning), and following conditioning in presence and absence of isoflurane.

2007-06-29 | E-GEOD-1779 | biostudies-arrayexpress

RNA-seq of mouse cortical tissue and astrocytes after anesthesia and induction of neuronal activity

Project description:General anesthesia is a common clinical procedure yet can result in long term CNS-adverse effects, particularly in the elderly, or dementia patients. Suppression of cortical activity is a key feature of the anesthetic-induced unconscious state, with activity being a well-described regulator of pathways important for brain health. However the extent to which the effects of anesthesia go beyond simple suppression of neuronal activity is incompletely understood, as are its effects on non-neuronal cell types such as astrocytes, which are important integrators of both neuronal activity and inflammatory signalling. In order to address these questions, we performed a combination of RNA-seq and TRAP-seq (Translating Ribosome Affinity Purification, where astrocyte-specific translating mRNAs are sequenced) on mouse cortical tissue and primary cortical neurons.

2023-08-01 | E-MTAB-13054 | biostudies-arrayexpress

sevoflurane exposures on neonatal and adult mice,LC-MSMS

Project description:Sevoflurane is the most commonly used general anesthetic in pediatric surgery, but it has the potential to be neurotoxic. Previous research found that long-term or multiple sevoflurane exposures could cause cognitive deficits in newborn mice but not adult mice, whereas short-term or single inhalations had little effect on cognitive function at both ages. The mechanisms behind these effects, however, are unclear. In the current study, 6- and 60-day-old C57bl mice in the sevoflurane groups were given 3% sevoflurane plus 60% oxygen for three consecutive days, each lasting 2 hours, while those in the control group only got 60% oxygen. The cortex tissues were harvested on the 8th or 62nd day. The tandem mass tags (TMT)pro-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysi were applied to analyze the influences of multiple sevoflurane anesthesia on the cerebral cortex in mice with various ages. A total of 6247 proteins were measured using the combined quantitative proteomics methods of TMTpro-labeled and LC-MS/MS, 443 of which were associated to the age-dependent neurotoxic mechanism of repeated sevoflurane anesthesia. Our findings would help to further the mechanistic study of age-dependent anesthetic neurotoxicity and contribute to seek for effective protection in the developing brain under general anesthesia.

2022-12-08 | PXD037294 | Pride

Anesthesia, TIVA, Balanced Anesthesia, NK Cell

Project description:Anesthetic method was reported to have an impact on postoperative long-term outcome in cancer patients. In this study, we will investigate the effect of different anesthetic methods on NK cell activity, cytokine response and postoperative outcome in colorectal cancer patients undergoing CRS and HIPEC. We will compare propofol-based total intravenous anesthesia (TIVA) with balanced anesthesia to determine the effect of propofol, inhalation agent, and opioid on tumor genesis, recurrence, NK cell activity, cytokine response, and postoperative outcome.

| 66979 | ecrin-mdr-crc

Gene expression profiles in liver of Sprague-Dawley rat using two types of anesthesia.

Project description:To reveal influence of anesthesia in toxicogenomics study, gene expression analysis of liver of Sprague-Dawley rat after isoflurane anesthesia or CO2/O2 anesthesia was performed. The liver samples were excised from each rat after isoflurane anesthesia or CO2/O2 anesthesia. The gene expression profiles in liver were measureed by Agilent microarray.

2015-07-24 | GSE71277 | GEO

Expression data from sevoflurane anesthesia treated rat

Project description:Long noncoding RNAs (lncRNAs) play important roles in brain function modulation and neurodegenerative diseases. However, whether lncRNA regulations are involved in the mechanisms of perioperative neurocognitive disorders (PNCD), especially in anesthesia related brain dysfunction, remains unknown. We explored the expression and regulation pattern profiles of lncRNAs in the hippocampus of aged rats after sevoflurane anesthesia with microarrays.

2020-12-29 | GSE139220 | GEO

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