Viral infections, neurodegenerative & psychiatric diseases: an arduous search for clues …

Viruses & Parkinson’s disease

Parkinson’s Disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra, resulting in resting tremor, rigidity, and bradykinesia. PD is characterized by the accumulation of the a-synuclein protein in Lewy body structures. Of note, a-synuclein aggregates have also been described in the enteric nervous system while the vagus nerve has been described as a potential path of entrance (by retrograde transport) of pathogens to the brain. Yet, whereas a-synuclein is constitutively expressed in neurons, its lack in knock-out mice does not alter the phenotype of the animals which breed normally, have a normal lifespan, do not seize, and have normal neuronal content and function (Beatman, Massey et al. 2015). Interestingly, there is a long history of links between viral infections and PD. The influenza virus, for example, has been suggested to be involved in PD, on the basis of clinical observations and epidemiological studies. The association of Parkinsonism with influenza (and many other viruses) dates back from the outbreak of Encephalitis Lethargica (see § “History”) and the postencephalitic Parkinsonism that took place after 1918. Even though the hypothesis that E.L. was a complication of influenza remains a matter of debate, epidemiological observations demonstrate a strong tie between the 1918 H1N1 influenza A pandemic (Spanish flu) and an increased incidence of PD (De Chiara, Marcocci et al. 2012). Other viruses have been suggested to potentially induce Parkinson symptoms. Thus, in some patients, acute viral infection of the substantia nigra pars compacta with the West Nile virus triggers encephalitis, resulting in clinical Parkinsonian symptoms. Interestingly, some authors have demonstrated increased viral growth when a-synuclein decreases, suggesting that the latter might function to inhibit viral infections in neurons as a restriction factor (Beatman, Massey et al. 2015). Neuroanatomical studies suggest that the olfactory bulb and the gastrointestinal neurons might be paths of entrance of viral neuroinvasion into the CNS. Could a viral infection spread to the CNS from peripheral gastrointestinal neurons and/or the olfactory bulb, spreading a-synuclein aggregation? Indeed, PD patients present prodromal symptoms featured by changes in smell and/or gastrointestinal symptoms long (sometimes by decades) before the clinical onset of PD. These observations are very reminiscent of the anosmia and ageusia which have been repeatedly described in Covid 19 patients. They again raise concern on the potential medium to long term impact that SARS Cov2 infection might have in terms of neurodegenerative and neuropsychiatric diseases (Serrano-Castro, Estivill-Torrús et al. 2020).

PP

Viruses & schizophrenia

“Schizophrenia” is a name that defines an etiologically heterogeneous disorder with probable multiple and complex pathophysiological mechanisms which remain however poorly defined. As such, ... read more