Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2021)

Astrocytes are a type of glial cell found in the CNS and play important physiological roles in maintaining homeostasis of the extracellular space. They are implicated in maintaining extracellular concentrations of certain ions and molecules, including the excitatory neurotransmitter glutamate. Astrocyte volume is strongly effected by changes in the extracellular environment, a phenomenon that is widely recognized and undisputed. Under both physiological and pathological circumstances, astrocyte volume changes can occur and have noticeable effects on the activity of adjacent neurons. This dissertation aimed to (1) characterize astrocyte volume increases that occur in the presence of elevated extracellular potassium, (2) isolate astrocyte-swelling-specific effects on neuronal excitability in a model of elevated extracellular potassium, and (3) ascertain the role of volume-regulated anion channel function in astrocyte volume change and alterations in neuronal excitability.

    Cover page: Astrocyte Mediation of Neuronal Activity Through Cellular Volume Change
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2017)
    BACKGROUND AND AIMS: M cells associated with organised lymphoid tissues such as intestinal Peyers patches provide surveillance of the intestinal lumen. Inflammation or infection in the colon can induce an M cell population associated with lymphoid infiltrates; paradoxically, induction is dependent on the inflammatory cytokine tumour necrosis factor [TNF]-α. Anti-TNFα blockade is an important therapeutic in inflammatory bowel disease, so understanding the effects of TNFα signalling is important in refining therapeutics. METHODS: To dissect pro-inflammatory signals from M cell inductive signals, we used confocal microscopy image analysis to assess requirements for specific cytokine receptor signals using TNF receptor 1 [TNFR1] and 2 [TNFR2] knockouts [ko] back-crossed to the PGRP-S-dsRed transgene; separate groups were treated with soluble lymphotoxin β receptor [sLTβR] to block LTβR signalling. All groups were treated with dextran sodium sulphate [DSS] to induce colitis. RESULTS: Deficiency of TNFR1 or TNFR2 did not prevent DSS-induced inflammation nor induction of stromal cell expression of receptor activator of nuclear factor kappa-B ligand [RANKL], but absence of TNFR2 prevented M cell induction. LTβR blockade had no effect on M cell induction, but it appeared to reduce RANKL induction below adjacent M cells. CONCLUSIONS: TNFR2 is required for inflammation-inducible M cells, indicating that constitutive versus inflammation-inducible M cells depend on different triggers. The inducible M cell dependence on TNFR2 suggests that this specific subset is dependent on TNFα in addition to a presumed requirement for RANKL. Since inducible M cell function will influence immune responses, selective blockade of TNFα may affect colonic inflammation.
      Top