Developmental, pharmacological, and experience-dependent regulation of nicotinic receptor-interacting Ly6 proteins

Betül Cinar

Studenteropgave: Speciale

Abstrakt

Proteins belonging to the Ly6 superfamily are believed to be allosteric modulators of nicotinic acetylcholine receptors (nAChRs) affecting synaptic plasticity, learning, and memory serving to prevent the effects of excitatory receptor signaling which causes neurodegeneration. The objective of this thesis was to study the expression, regulation, and localization of the Ly6 superfamily under various conditions in rats by means of RT-qPCR and/or western blotting. A postnatal developmental study was conducted to examine the expression profiles of the Ly6 superfamily. The expression of Ly6 proteins in different neuronal and non-neuronal tissues was studied to evaluate the tissue type-dependent distribution of Ly6 proteins. Furthermore, a BS3 cross-linkage assay was carried out where proteins located at cellular surfaces were cross-linked with BS3 with the purpose of investigating cell surface levels of Ly6 proteins. Experiments in which male rat pups were exposed to nicotine and/or the partial α7 agonist, SSR-180711, pre- and postnatally were conducted to study putative alterations in the expression of Ly6 proteins. Finally, acute and chronic forced exercise studies were conducted to investigate the expression of Ly6 proteins. Postnatal expression profiles of the Ly6 superfamily revealed upregulation of the Ly6 superfamily associated with aging. The majority of the Ly6 proteins exhibited tissue-restrictive expression profiles being predominantly located in neuronal tissues, namely cortex and cerebellum. Furthermore, cell surface cross-linkage studies revealed both intracellular and cell surface expression of Ly6 proteins exhibiting brain region-specificity. Neither pre- nor postnatal nicotine and/or SSr-180711 exposure affected Ly6 protein levels. Finally, acute and chronic exercise studies did not indicate any impact of exercise on the expression of Ly6 proteins. Altogether, these results suggest that expression of the Ly6 superfamily is robust to perturbations which allows minimal interference by other factors like nAChR agonists and synaptic plasticity-increasing interferences such as exercise.

UddannelserMolekylærbiologi, (Bachelor/kandidatuddannelse) KandidatMedicinalbiologi, (Bachelor/kandidatuddannelse) Kandidat
SprogEngelsk
Udgivelsesdato10 okt. 2012
VejledereMorten S Thomsen & Anders B Klein

Emneord

  • memory
  • PSCA
  • Ly6
  • learning
  • western blot
  • neuromodulator
  • Lypd6
  • RIC-3
  • neurobiology
  • synaptic plasticity
  • Ly6H
  • nicotinic acetylcholine receptors
  • Lynx2
  • RT-qPCR
  • Lynx1