Time course of dopamine neuron loss and glial response in the 6-OHDA striatal mouse model of Parkinson's disease

摘要: The 6-hydroxydopamine (6-OHDA) neurotoxic lesion of the midbrain dopamine (DA) system is one most widely used techniques for modelling Parkinson's disease in rodents. majority studies using this approach, however, largely limit their analysis to lesioning acutely, and looking at behavioural deficits number surviving tyrosine hydroxylase (TH)-stained cells midbrain. Here we have analysed additional characteristics that occur following intrastriatal delivery 6-OHDA, providing better understanding neurodegenerative process. Female C57/Black mice were given lesions 10 weeks old, killed several different time points postoperatively (3 6 h, 1, 3, 6, 9 12 days). While detrimental effect toxin on TH+ fibres striatum was immediate, found loss dendritic fibres, reduction cell size intensity TH expression, eventual neurons substantia nigra delayed days post-surgery. We also investigated expression various transcription factors proteins expressed by DA lesioning, observed changes Aldh1a1 (aldehyde dehydrogenase 1 family, member A1) as process evolved. Extracellularly, looked microglia astrocytes reaction 6-OHDA striatal lesion, a delay response proliferation nigra. In summary, work highlights aspects mouse model can be applied future therapeutic interventions.