Occurrence of neuronal dysfunction in mice with virus- or toxic-induced lesions in the central nervous system

Diseases of the central nervous system (CNS) often include neuronal damage. This study examined proteins crucial to apoptosis and neuronal signalling for identifying causes of neuronal dysfunction in two animal models: Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) and ethidium bromide (EtBr)-induced focal spinal cord injury. Transcriptomic analysis revealed increased levels of pro-apoptotic molecules including Caspase 8 (Casp8) and Cathepsin B (CTSB), but no significant changes in synaptic proteins including synaptophysin, synaptosomal-associated protein of 25 kDa (SNAP25) and postsynaptic density protein of 95 kDa (PSD95). Immunohistochemistry showed increased levels of pro-apoptotic proteins Casp8 and CTSB in the grey matter of TMEV-IDD but reduced levels of these proteins following EtBr injection. Synaptophysin, a marker for neuronal signalling, was reduced in the grey matter in both models. Drebrin, a protein related to neuronal plasticity, was significantly reduced in the grey matter of EtBr-injected mice, but increased in the white matter of TMEV-infected mice. Summarized, the upregulation of pro-apoptotic molecules in TMEV-IDD without apoptotic neurons suggests an incomplete apoptosis, while their reduction in EtBr-injected mice may indicate a reversible neuronal damage. The reduction of synaptophysin in both models indicates a possible impairment of synaptic transmission while the reduction of Drebrin in EtBr-injected mice may be associated with a reduced synaptic plasticity.