engleski

Extracellular signal-regulated kinase signalling in the hippocampus of a rat model of sporadic Alzheimer's disease

Introduction: The pathogenesis of sporadic Alzheimer’s disease (sAD) has been associated with altered signalling in the mitogen-activated protein kinase (MAPK) pathways. The extracellular signal-regulated kinase (ERK), a MAPK subfamily member, was found activated in vulnerable cerebral neurons of sAD patients. We aimed to explore ERK signalling in the brain of streptozotocin (STZ)-intracerebroventricularly (icv) treated rats, a new experimental sAD model. Materials and methods: Three month-old male Wistar rats were injected intracerebroventricularly with STZ (3 mg/kg) or vehicle (controls). Cognitive functions were tested by Morris Water Maze Swimming Test before sacrifice, one and nine months following the STZ-icv treatment. Protein expression of phosphorylated and total tau protein (p-tau and t-tau) and pERK and tERK was measured in the hippocampus by SDS-PAGE electrophoresis, followed by immunoblotting. Data were analysed by Mann-Whitney U test (p<0.05). Results: One month after the STZ-icv treatment only protein expression of pERK was found significantly increased (+23%). Signalling dysfunction progressed up to 9 months after the STZ-icv treatment when further significant increment in pERK expression (+38%) accompanied by decreased t-ERK expression (-20%) was found followed by increased p/t-tau ratio (+39% ; p=0.08). Cognitive deficits of STZ-icv treated rats were present at both time-points (-30% and -39%). Conclusion: STZ-induced activation of hippocampal ERK pathway, known to be involved in cellular responses to pro-inflammatory signals, supports the similarity of inflammatory processes found in the brain of STZ-icv model and sAD patients. Presented results provide further evidence of STZ-icv rat model being a representative sAD model. Acknowledgment: Supported by MZOŠ and DAAD.

extracellular signal-regulated kinase; streptozotocin; Alzheimer's disease

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