Shedding Light on the Red Nucleus in Parkinsonisms: A Neuropathological Study

Restricted (Penn State Only)
- Author:
- Johnson, Melinda
- Graduate Program:
- Anatomy
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 26, 2024
- Committee Members:
- Patricia Mclaughlin, Program Head/Chair
Xuemei Huang, Chair & Dissertation Advisor
Sharon Huang, Outside Unit Member
Pat Mclaughlin, Outside Field Member
James Connor, Major Field Member
Loren Evey, Outside Field Member - Keywords:
- parkinsonisms
Parkinson's disease
progressive supranuclear palsy
multiple system atrophy
corticobasal degeneration
atypical parkinsonisms
substantia nigra
red nucleus
pathology
neuropathology
MRI
susceptibility MRI
iron
movement disorders
neurology
brain - Abstract:
- Parkinsonisms is a clinical term used to describe a group of neurodegenerative disorders that are characterized by motor symptoms including bradykinesia, rigidity, resting tremor, and postural and gait dysfunction. Among all parkinsonisms, idiopathic, or classic, Parkinson’s disease (PD) is the most common form. Other forms are grouped together as atypical parkinsonian syndromes. Dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) comprise the majority of atypical parkinsonian syndromes. Despite having mostly heterogeneous clinical and pathological features, PD and atypical parkinsonisms share many motor symptoms that are largely attributed to dysfunction of basal ganglia. The basal ganglia are a group of interconnected subcortical nuclei that play a role in motor control by influencing the quality and correctness of movement. Among basal ganglia structures, the substantia nigra pars compacta (SNc) are a key pathological locus of parkinsonisms, both classic PD and atypical parkinsonian syndromes. The SNc is located in the ventral midbrain and is rich in iron. While there are many hypotheses, it remains unclear what makes this region particularly susceptible to the neurodegeneration seen in these diseases. In addition to basal ganglia, the cerebellum is another key structure involved in motor output. In parkinsonisms, structures related to cerebellar motor pathways are known to be affected, albeit the nature of their involvement varies. In some cases, such as MSA, these structures undergo atrophic pathology; whereas in others (e.g., PD), they seem to be more resilient and even have been suggested to serve a compensatory role. The red nucleus (RN) is an integral part of cerebellar pathways. Similar to the SNc, it is situated in the ventral midbrain and is rich in iron. There is, however, a lack of existing evidence on if or how the RN may be involved in parkinsonisms. In this dissertation, I discuss in great depths the issues outlined above and present original research that advances our understanding of the RN in parkinsonisms. In the first chapter, I introduce classic PD, its history, epidemiology, and clinical features, as well as evolving concepts of atypical parkinsonisms, and the roles of the SNc and RN. In the second chapter, I discuss in detail my work examining in vivo susceptibility magnetic resonance imaging (MRI) correlates and postmortem neuropathological findings from the RN compared with the SNc in parkinsonism subjects. In the third chapter, I discuss in detail my work comparing postmortem SNc and RN histopathology patterns in parkinsonism patients, with an expanded cohort of healthy controls. In the last chapter, I summarize my findings and future directions for the study of the RN in parkinsonisms. As a whole, this dissertation addresses key gaps in our current knowledge and lays important groundwork for future investigations.