Commentary: Evaluation of Models of Parkinson's Disease

In the recently published review article by Jagmag et al. (2016), some currently available neurotoxin based and genetic models of Parkinson's disease (PD) were described, highlighting the advantages and disadvantages of preclinical models use to knowledge of PD. The aim of this commentary is to shed light and to make a reflection on some fundamental issues involving the pathophysiology of PD and additionally bring to the discussion the animal model of PD based on the administration of reserpine (RES). The pathological hallmark of PD involves the progressive loss of neurons in the substantia nigra pars compacta (SNpc) (Politis and Niccolini, 2015). However, a large body of evidences implies that the PD pathology is a multisystemic degenerative process that involves other neurotransmitters such as serotonin (5-HT) and norepinephrine (NE) (Deusser et al., 2015; Liu et al., 2015; Politis and Niccolini, 2015). It has been demonstrated that the serotonergic system may be the most critical neurochemical system involved in the pathology of PD, after the dopaminergic system (Huot and Fox, 2013; Liguori et al., 2015). Changes in serotonin levels may be a contributing factor to PD symptomatology, in particular, non-motor disturbances (Loane et al., 2013). Patients with PD show loss of serotonergic neurons in the brainstem raphe nuclei (Braak et al., 2003) and reduced expression of tryptophan hydroxylase type 2 (TPH2) in the median raphe nucleus (MnR) (Kovacs et al., 2003). According to Braak staging of PD pathology, serotonergic cell loss in the raphe nuclei is evident prior to nigrostriatal dopaminergic degeneration. Interestingly, the pattern of serotonergic loss also seems to be different from that observed in the dopaminergic system (Politis and Loane, 2011). Additionally, other neuronal systems, including noradrenergic locus coeruleus, are also affected in PD (see review in Jellinger, 1999) and they have been linked to non-motor symptoms of PD as well. Thereby, these evidences of alterations in the raphe nuclei and catecholaminergic nuclei highlight the importance of looking beyond the nigrostriatal system in the PD study, in order to elucidate the underlying mechanisms of deficits of other neurotransmitter systems in the physiopathology of PD and provide useful information for the development of therapeutic strategies for this disease. In the paper, Jagmag et al. (2016) highlight toxins widely used as animal models of PD. The toxin 1-methyl-4-phenylpyridinium (MPP+), active metabolite of MPTP, is taken up into dopaminergic terminals by the dopamine transporter (DAT) showing the high affinity for (6-OHDA) is …