Limbic Encephalitis Brain Damage Induced by Cocal Virus in Adult Mice Is Reduced by Environmental Enrichment: Neuropathological and Behavioral Studies

Abstract

We previously demonstrated, using the Piry virus model, that environmental enrichment promotes higher T-cell infiltration, fewer microglial changes, and faster central nervous system (CNS) virus clearance in adult mice. However, little is known about disease progression, behavioral changes, CNS cytokine concentration, and neuropathology in limbic encephalitis in experimental models. Using Cocal virus, we infected C57Bl6 adult mice and studied the neuroanatomical distribution of viral antigens in correlation with the microglial morphological response, measured the CNS cytokine concentration, and assessed behavioral changes. C57Bl6 adult mice were maintained in an impoverished environment (IE) or enriched environment (EE) for four months and then subjected to the open field test. Afterwards, an equal volume of normal or virus-infected brain homogenate was nasally instilled. The brains were processed to detect viral antigens and microglial morphological changes using selective immunolabeling. We demonstrated earlier significant weight loss and higher mortality in IE mice. Additionally, behavioral analysis revealed a significant influence of the environment on locomotor and exploratory activity that was associated with less neuroinvasion and a reduced microglial response. Thus, environmental enrichment was associated with a more effective immune response in a mouse model of limbic encephalitis, allowing faster viral clearance/decreased viral dissemination, reduced disease progression, and less CNS damage.

Lifestyle-dependent microglial plasticity: training the brain guardians

“…In cocal virus infection, mice dwelling in standard environment demonstrated significant weight loss and higher mortality as compared with animals exposed to environmental stimulation. Additionally, enriched environment led to better locomotor and exploratory activity associated with less neuroinvasion and reduced microglial reactivity, revealing that enriched environment drives a more effective immune response in a mouse model of virus encephalitis [90].…”

Unwanted Exacerbation of the Immune Response in Neurodegenerative Disease: A Time to Review the Impact

“…SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection (Liu J. M. et al, 2021). Its neuroinvasion route through nasal epithelium (Yachou et al, 2020) is similar to that of many other RNA viruses (Freitas et al, 2020;Awogbindin et al, 2021), including the Piry arbovirus used to infect the mouse prion disease model (de Sousa et al, 2015). We found that the Piry virus interaction with ME7-associated chronic neurodegeneration induces progressive exacerbation of microglia and astrocyte morphological alterations.…”