Structural brain changes in Ser129-phosphorylated alpha-synuclein rats based on voxel-based morphometry

Parkinson's disease has become one of the most common neurodegenerative diseases. Pathological changes typically manifest following dopaminergic neuron loss in the substantia nigra and abnormal alpha-synuclein (α-syn) aggregation in the neurons. α-Syn is the major component of Lewy bodies. However, research pertaining to the spread of abnormal α-syn aggregations, which results in specific damage to the brain structure and function, is lacking. In the present study, full-length human α-syn fibrils were injected into the medial forebrain bundle of rats, with an experimental endpoint of 6 months. Histological analysis was conducted to observe the pathological progress of abnormal endogenous α-syn aggregation and nerve fiber quality. Changes in gray and white matter integrity were quantitatively analyzed using voxel-based morphometry (VBM). Behavioral changes were observed over the 6-month period. Histological analysis showed reduced dopamine transporter levels in the striatum of the experimental rats; widespread abnormal endogenous α-syn accumulation; and damaged, sparse, and disordered nerve fibers in the experimental group. VBM showed that at 6 months after surgery, bilateral anterior limbic, bilateral inferior limbic, right hippocampal, and right cortical volumes had reduced, whereas thalamic volume had increased in the experimental group compared with that in the control group. Damage to the limbic and thalamic fiber structure may occur in the earlier stages of Parkinson's disease.