Cetaceans as Potentially Useful Animal Models for Human Central Nervous System Disorders

Stranded cetaceans provide a unique opportunity for gaining insight into their increasingly threatened health and conservation. Within this framework, cetaceans could also serve as potentially useful animal models for human central nervous system (CNS) diseases (Di Guardo, 2023).

 This holds especially true for Alzheimer’s disease (AD) and subacute sclerosing panencephalitis (SSPE), with the former representing the most frequently occurring form of dementia across the globe, although it cannot yet rely on animal models able to recapitulate the whole spectrum of AD neuropathological features, i.e. amyloid-β (Aβ) extra-neuronal plaques and hyperphosphorylated tau protein neurofibrillary tangles (Querfurth and LaFerla, 2010).

As far as SSPE is specifically concerned, this is a rare brain disorder observed in a small subset of Measles virus (MeV)-infected patients, for which striped dolphins (Stenella coeruleoalba) infected by Dolphin morbillivirus (DMV) - a Cetacean morbillivirus (CeMV) strain responsible for several cetacean mass mortality outbreaks throughout the last 35 years (Jo et al., 2018) - could candidate themselves as potentially useful  animal models, provided they may also develop a  peculiar, “brain-only” form of infection (Di Guardo and Mazzariol, 2016). Noteworthy, SSPE-like lesions were detected in 25% of striped dolphins found beached along the Mediterranean Spanish coast after the 2006–2007 DMV epidemic (Soto et al., 2011), while the neuronal and glial cell populations infected by DMV in striped dolphins with SSPE-like brain lesions has been additionally reported (Luca' et al., 2017). Notwithstanding this, the cell receptor(s) allowing viral persistence and spread across the brain from SSPE-affected people as well as from striped dolphins carrying SSPE-like alterations is/are still far from being elucidated (Watanabe et al., 2019; Di Guardo, 2023). Conversely, MeV phosphoprotein (P), matrix (M) and fusion (F) gene mutations may promote viral spread in infected human brains, with subsequent SSPE development (Watanabe et al., 2019; Busch et al., 2021; Shirogane et al., 2021; Zinzula et al., 2022).

Based upon the above and taking into special account that we are dealing with merely descriptive findings, a much deeper genetic, biomolecular and phenotypical characterization of SSPE-like brain lesions in striped dolphins is required before drawing the conclusion they mirror (or not) their human “counterparts.”

Cetacean CNS disorders and, more in general, all disease conditions spontaneously occurring in dolphins and whales may be also relevant from a “One Health” perspective, thus serving as potential “mirrors” for their human “analogues,” and marine mammal pathologists as well as the entire scientific biomedical community should be made properly aware of this. As a matter of fact, gaining additional insight into cetacean AD-like and SSPE-like brain alterations and, more in general, into cetacean CNS disorders may represent an intriguing opportunity from the comparative pathology standpoint. Within this framework, the potential impact of CNS diseases on cetacean health and conservation should be carefully assessed by means of in-depth post mortem and laboratory investigations on stranded individuals (Di Guardo, 2023). In this respect, cetacean CNS disorders could also benefit from ad hoc investigation protocols allowing to characterize the differential expression of relevant host genes driving disease susceptibility and/or resistance (Zinzula et al., 2022).



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