The expression of heme oxygenase 1 (HO-1) in the cortex and hippocampus is higher in Alzheimer's disease (AD) and mild cognitive impairment patients than healthy individuals, and epidemiological studies suggest that HO-1 is an important factor for AD. However, its influence on nerve function is poorly understood. Here, we studied the effect of the overexpression of HO-1 on the cognitive and synaptic plasticity in 3-month-old mice. We found that the overexpression of HO-1 induced spatial learning and memory deficits with an apparent decrease of AMPKR, NMDAR, postsynaptic density protein 95, synapsin I, synaptophysin, and microtubule-associated protein 2, all of which are memory-related synaptic proteins. Concurrently, HO-1 could co-express and induce the aggregation of A beta(42) and A beta oligomer in the hippocampus area. Additionally, our research is the first to demonstrate that HO-1 changes the morphology of the synapse to impair the neural circuit. These results indicate that the overexpression of HO-1 can damage synaptic plasticity in early stages to induce AD-like pathology and cognitive abnormality in mice.
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