Expression of Tgfβ1 and Inflammatory Markers in the 6-hydroxydopamine Mouse Model of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by loss of midbrain dopaminergic (mDA) neurons in the substantia nigra (SN). Microglia-mediated neuroinflammation has been described as a common hallmark of PD and is believed to further trigger the progression of neurodegenerative events. Injections of 6-hydroxydopamine (6-OHDA) are widely used to induce degeneration of mDA neurons in rodents as an attempt to mimic PD and to study neurodegeneration, neuroinflammation as well as potential therapeutic approaches. In the present study, we addressed microglia and astroglia reactivity in the SN and the caudatoputamen (CPu) after 6-OHDA injections into the medial forebrain bundle (MFB), and further analyzed the temporal and spatial expression patterns of pro-inflammatory and anti-inflammatory markers in this mouse model of PD. We provide evidence that activated microglia as well as neurons in the lesioned SN and CPu express Transforming growth factor β1 (Tgfβ1), which overlaps with the downregulation of pro-inflammatory markers Tnfα, and iNos, and upregulation of anti-inflammatory markers Ym1 and Arg1. Taken together, the data presented in this study suggest an important role for Tgfβ1 as a lesion-associated factor that might be involved in regulating microglia activation states in the 6-OHDA mouse model of PD in order to prevent degeneration of uninjured neurons by microglia-mediated release of neurotoxic factors such as Tnfα and nitric oxide (NO).

Physical exercise and human adipose‐derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson's disease

“…Tyrosine hydroxylase immunohistochemistry stains showed dopaminergic depletion in the impairment side compared to the contralateral non‐injected side (healthy side) (see Figure ). Results similar to ours in terms of cellular morphology and distribution have been demonstrated in previous publications (Haas et al, ).…”

Altered mGluR5 binding potential and glutamine concentration in the 6-OHDA rat model of acute Parkinson's disease and levodopa-induced dyskinesia

“…Despite we showed altered [ 18 F]FPEB binding potential, pointing to a role for mGluR5 in PD and LID, other contributing mechanisms such as alterations in receptor affinity, conformational state, and neuroinflammation cannot be fully excluded. Recently, Haas et al showed increased microglial and astrocyte infiltration into the CP of 6-OHDA-lesioned mice, targeted intranigrally, albeit limited at 14 days post-surgery (Haas, et al, 2016).…”

Vascular inflammation is a risk factor associated with brain atrophy and disease severity in Parkinson’s disease: a case-control study

“…MiRNA-22 regulates inflammation and angiogenesis by targeting VEcadherin [53] and miRNA-29a can modulate the angiogenic properties of human endothelial cells [19] and be upregulated by proinflammatory cytokine transforming growth factor β (TGF-β) [54].The miRNA is also involved in neuron growth [55] and atherosclerosis formation [56].An in vitro study found that miRNA-29a overexpression promoted the formation of new blood vessels, while miR-29a suppression completely blocked TGF-β1-stimulated angiogenesis [54]. TGF-β1 expression was increased in striatal neurons and in activated microglia on the lesion side of a 6-hydroxydopamineinduced PD mouse model in one in vivo study [57] and was elevated in the CSF fluid of PD patients in an in vitro study, indicating that it acts as a neuroprotective factor in injured brains. Another previous study revealed the down-regulation of miR29a in treatment-naïve PD patients [58], but up-regulation in L-dopa-treated PD patients has also been observed [20].…”