Impaired c-Fos and polo-like kinase 2 induction in the limbic system of fear-conditioned ?-synuclein transgenic mice.

ABSTRACT: ?-Synuclein (?SYN) is genetically and neuropathologically linked to a spectrum of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, and related disorders. Cognitive impairment is recapitulated in several ?SYN transgenic mouse lines. However, the mechanisms of dysfunction in affected neurons are largely unknown. Here we measured neuronal activity induced gene products in the limbic system of ?SYN transgenic mice upon fear conditioning (FC). Induction of the synaptic plasticity marker c-Fos was significantly reduced in the amygdala and hippocampus of (Thy1)-h[A30P]?SYN transgenic mice in an age-dependent manner. Similarly, the neuronal activity inducible polo-like kinase 2 (Plk2) that can phosphorylate ?SYN at the pathological site serine-129 was up-regulated in both brain regions upon FC. Plk2 inductions were also significantly impaired in aged (Thy1)-h[A30P]?SYN transgenic mice, both in the amygdala and hippocampus. Plk2 inductions in the amygdala after FC were paralleled by a small but significant increase in the number of neuronal cell bodies immunopositive for serine-129 phosphorylated ?SYN in young but not aged (Thy1)-h[A30P]?SYN transgenic mice. In addition, we observed in the aged hippocampus a distinct type of apparently unmodified transgenic ?SYN profiles resembling synaptic accumulations of ?SYN. Thus, the cognitive decline observed in aged ?SYN transgenic mice might be due to impairment of neurotransmission and synaptic plasticity in the limbic system by distinct ?SYN species.

SUBMITTER: Schell H 

PROVIDER: S-EPMC3507699 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature