Abstract
The aim of the study was to examine the Braak’s hypothesis to explain the spreading and distribution of the neuropathological changes observed in the course of Parkinson’s disease among ascending neuroanatomical regions. We investigated the neurotransmitter levels (monoamines and amino acid concentration) as well as tyrosine hydroxylase (TH) and transglutaminase-2 (TG2) mRNA expression in the mouse striata (ST) after intracerebral α-synuclein (ASN) administration into gigantocellular reticular nucleus (Gi). Male C57BL/10 Tar mice were used in this study. ASN was administrated by stereotactic injection into Gi area (4 μl; 1 μg/μl) and mice were decapitated after 1, 4 or 12 weeks post injection. The neurotransmitters concentration in ST were evaluated using HPLC detection. TH and TG2 mRNA expression were examined by Real-Time PCR method. At 4 and 12 weeks after ASN administration we observed decrease of DA concentration in ST relative to control groups and we found a significantly higher concentration one of the DA metabolites—DOPAC. At these time points, we also noticed the increase in DA turnover determined as DOPAC/DA ratio. Additionally, at 4 and 12 weeks after ASN injection we noted decreasing of TH mRNA expression. Our findings corresponds with the Braak’s theory about the presence of the first neuropathological changes within brainstem and then with time affecting higher neuroanatomical regions. These results obtained after administration of ASN monomers to the Gi area may be useful to explain the pathogenesis of Parkinson’s disease.
Highlights
Parkinson’s disease (PD) is a one of the most common neurodegenerative disease affecting the central nervous system (CNS) characterized by the multitude of motor and nonmotor clinical symptoms [1]
after intracerebral α-synuclein (ASN) administration caused an increase in dopamine turnover (DOPAC/DA) in 4 and 12 weeks (Fig. 2e) and both, 3-MT/DA and homovanillic acid (HVA)/ DA ratios in 4 weeks compared to NaCl groups (Fig. 2fg)
The initial neuropathological changes are observed in medulla oblongata, ventral tegmental area and olfactory bulbs [32]
Summary
Parkinson’s disease (PD) is a one of the most common neurodegenerative disease affecting the central nervous system (CNS) characterized by the multitude of motor and nonmotor clinical symptoms [1]. The hallmark of PD motor manifestation include progressive tremor, rigidity, bradykinesia and postural instability [4]. The non-motor symptoms include, but are not limited to cognitive impairment, sleep disturbances, autonomic dysfunction and depression [5]. The major pathophysiological process occurring in the course of PD is associated with the degeneration of dopaminergic neurons in the substantia nigra (SN) and in its pars compacta (SNpc) within brainstem [6]. In this case, progressive loss of dopaminergic neurons results in reduction of the dopamine (DA) and its metabolites
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