Related Experiment Video

Updated: Jul 16, 2026

Generation of Single-Cell Suspensions from Mouse Neural Tissue
11:17

Generation of Single-Cell Suspensions from Mouse Neural Tissue

Published on: July 7, 2009

Genes involved in the balance between neuronal survival and death during inflammation

Isaias Glezer1, Ariel Chernomoretz, Samuel David

  • 1Laboratory of Molecular Endocrinology, Centre Hospitalier de l'Université Laval (CHUL) Research Center and Department of Anatomy and Physiology, Laval University, Laurier, Québec, Canada.

Plos One
|March 22, 2007
PubMed

Insights

Glucocorticoid signaling loss impairs neuroprotective genes like ceruloplasmin (Cp) during brain inflammation. Cp deficiency exacerbates neurodegeneration, highlighting its role in CNS immune response and iron metabolism.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Neuroinflammation

Background:

  • Glucocorticoids regulate innate immunity, and their absence can harm neural tissue.
  • Understanding gene regulation during inflammatory responses in the central nervous system (CNS) is crucial.

Purpose of the Study:

  • To identify genes involved in the switch between cell survival and death during acute inflammation without glucocorticoid signaling.
  • To investigate the role of ceruloplasmin (Cp) in neuroprotection during inflammatory conditions.

Main Methods:

  • Oligonucleotide microarray analysis after intracerebral lipopolysaccharide (LPS) administration.
  • Gene expression profiling in the striatum following glucocorticoid receptor blockage.
  • Phenotypic analysis of Cp-deficient mice under inflammatory conditions.

Main Results:

  • More genes showed impaired transcription than exacerbation upon glucocorticoid receptor blockage after LPS administration.
  • Ceruloplasmin (Cp), involved in iron metabolism, was identified as an impaired gene.
  • Cp-deficient mice exhibited increased iron accumulation, demyelination, and neurovascular reactivity upon LPS exposure or pneumococcal meningitis.

Conclusions:

  • Cp induction by microglia and endothelial cells is a neuroprotective mechanism during inflammation.
  • The study identified key genes regulating the innate immune response in the CNS.
  • Findings clarify mechanisms of protection versus damage in CNS inflammatory conditions.

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...