Expression of NgR1-antagonizing proteins decreases with aging and cognitive decline in rat hippocampus

Cell Mol Neurobiol. 2013 May;33(4):483-8. doi: 10.1007/s10571-013-9929-4. Epub 2013 Mar 24.

Abstract

The myelin-associated inhibitor/Nogo-66 receptor 1 (NgR1) pathway directly functions in negative modulation of structural and electrophysiological synaptic plasticity. A previous study has established an important role of NgR1 pathway signaling in cognitive function, and we have demonstrated that multiple components of this pathway, including ligands, NgR1 co-receptors, and RhoA, are upregulated at the protein level specifically in cognitively impaired, but not age-matched cognitively intact aged rats. Recent studies have identified two novel endogenous NgR1 antagonists, LOTUS and LGI1, and an alternative co-receptor, ADAM22, which act to suppress NgR1 pathway signaling. To determine whether these endogenous NgR1-inhibiting proteins may play a compensatory role in age-related cognitive impairment by counteracting overexpression of NgR1 agonists and co-receptors, we quantified the expression of LOTUS, LGI1, and ADAM22 in hippocampal CA1, CA3 and DG subregions dissected from mature adult and aged rats cognitively phenotyped for spatial learning and memory by Morris water maze testing. We have found that endogenous inhibitors of NgR1 pathway action decrease significantly with aging and cognitive decline and that lower expression levels correlate with declining cognitive ability, particularly in CA1 and CA3. These data suggest that decreased expression of NgR1-antagonizing proteins may exert a combinatorial effect with increased NgR1 signaling pathway components to result in abnormally strong suppression of synaptic plasticity in age-related cognitive impairment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism*
  • Aging / metabolism*
  • Animals
  • Cognition Disorders / metabolism*
  • Cognition Disorders / physiopathology
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Memory
  • Models, Biological
  • Myelin Proteins / antagonists & inhibitors*
  • Myelin Proteins / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity
  • Nogo Receptor 1
  • Proteins / metabolism*
  • Rats
  • Rats, Inbred F344
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / metabolism

Substances

  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • LOTUS protein, rat
  • Lgi1 protein, rat
  • Myelin Proteins
  • Nerve Tissue Proteins
  • Nogo Receptor 1
  • Proteins
  • Receptors, Cell Surface
  • Rtn4r protein, rat
  • Adam22 protein, rat
  • ADAM Proteins