Unilateral Intrastriatal 6-Hydroxydopamine Lesion in Mice: A Closer Look into Non-Motor Phenotype and Glial Response

Abstract

Parkinson’s disease (PD) is a prevalent movement disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). The 6-hydroxydopamine (6-OHDA) lesion is still one of the most widely used techniques for modeling Parkinson’s disease (PD) in rodents. Despite commonly used in rats, it can be challenging to reproduce a similar lesion in mice. Moreover, there is a lack of characterization of the extent of behavioral deficits and of the neuronal loss/neurotransmitter system in unilateral lesion mouse models. In this study, we present an extensive behavioral and histological characterization of a unilateral intrastriatal 6-OHDA mouse model. Our results indicate significant alterations in balance and fine motor coordination, voluntary locomotion, and in the asymmetry’s degree of forelimb use in 6-OHDA lesioned animals, accompanied by a decrease in self-care and motivational behavior, common features of depressive-like symptomatology. These results were accompanied by a decrease in tyrosine hydroxylase (TH)-labelling and dopamine levels within the nigrostriatal pathway. Additionally, we also identify a marked astrocytic reaction, as well as proliferative and reactive microglia in lesioned areas. These results confirm the use of unilateral intrastriatal 6-OHDA mice for the generation of a mild model of nigrostriatal degeneration and further evidences the recapitulation of key aspects of PD, thereby being suitable for future studies beholding new therapeutical interventions for this disease.

Africanized Bee Venom (Apis mellifera Linnaeus): Neuroprotective Effects in a Parkinson’s Disease Mouse Model Induced by 6-hydroxydopamine

“…Studies using genetic models have gained strength in recent years, but it should be noted that the experimental model chosen must be focused on the mechanism that is intended to be addressed, the purpose of the study—in this case, neuroinflammation that results from oxidative stress—and not on mutations that are causally linked to familial cases of PD in humans. Therefore, the 6-OHDA model can mimic not only the behavioral deficits associated with PD but also other histological changes other than nigrostriatal degeneration, such as the glial response [ 30 , 31 ].…”

Non-motor manifestation of Parkinson's disease: a cross-sectional study in a teaching hospital in Jordan

“…There has been significant progress in understanding the relationship of gut microbiota regulation and neurodegenerative disease [21], their role in misfolding proteins like alpha synuclein in PD [22]. The finding of peripheral biomarkers for neurodegenerative disorders [23] and the relevant experimental models like the unilateral intralesional 6 hydroxydopamine lesions in mice [24] that showed evidence for non-motor manifestations in this PD model will advance our knowledge in this field. In addition to this, the ongoing efforts to reach personalized medical care based on certain markers in Alzheimer disease and PD [25] will lead to better understanding of the pathophysiology of degenerative neurological disorder and better avenues for new prophylactic and therapeutic options.…”

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase 1 Influenced the Age Onset of Parkinson's Disease

“…In addition to the age, which is the most important risk factor for neurodegenerative disease, genetic, epigenetic, environmental and lifestyle are initiation factors which play a role in the pathogenesis of PD [16,90,[103][104][105][106][107][108][109][110][111][112][113]. The preclinical studies, and diagnostic precision of PD are under extensive research, applying in vitro, in vivo, and in silico methodologies [114][115][116][117][118][119]. Until now, 21 PARK genes have been described in human genome as causative factors of the disease, furthermore, genetic variants of 26 loci have been shown to be important risk modifiers for PD.…”