Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor system affecting balance and muscle movement. The cause of MSA is unknown, no definitive risk factors have been identified, and there is no cure or effective treatment. The definitive pathology of MSA is the presence of alpha-synuclein aggregates in the brain and therefore MSA is classified as an alpha-synucleinopathy, together with Parkinson's disease and dementia with Lewy bodies. Although the molecular mechanisms of misfolding, fibrillation and aggregation of alpha-synuclein partly overlap with other alpha-synucleinopathies, the pathological pathway of MSA is unique in that the principal site for alpha-synuclein deposition is in the oligodendrocytes rather than the neurons. The sequence of pathological events of MSA is now recognized as abnormal protein redistributions in oligodendrocytes first, followed by myelin dysfunction and then neurodegeneration. Oligodendrocytes are responsible for the production and maintenance of myelin, the specialized lipid membrane that encases the axons of all neurons in the brain. Myelin is composed of lipids and two prominent proteins, myelin basic protein and proteolipid protein. In vitro studies suggest that aberration in protein distribution and lipid transport may lead to myelin dysfunction in MSA. The purpose of this perspective is to bring together available evidence to explore the potential role of alpha-synuclein, myelin protein dysfunction, lipid dyshomeostasis and ABCA8 in MSA pathogenesis.
alpha-Synuclein ; Autonomic Nervous System ; Axons ; Blood Pressure ; Brain ; Cerebellar Ataxia ; Dementia ; Heart Rate ; Lewy Bodies ; Membranes ; Multiple System Atrophy* ; Myelin Proteins ; Myelin Sheath* ; Neurodegenerative Diseases ; Neurons ; Oligodendroglia ; Parkinson Disease ; Parkinsonian Disorders ; Pathology ; Risk Factors ; Urinary Bladder

The hippocampus and olfactory bulb incorporate new neurons migrating from neurogenic regions in the brain. Hippocampal atrophy is evident in numerous neurodegenerative disorders, and altered hippocampal neurogenesis is an early pathological event in Alzheimer's disease. We hypothesized that hippocampal neurogenesis is affected by olfactory stimuli through the neural pathway of olfaction-related memory. In this study, we exposed mice to novel pleasant odors for three weeks and then assessed the number of neurons, non-neuronal cells (mainly glia) and proliferating cells in the hippocampus and olfactory bulb, using the isotropic fractionator method. We found that the odor enrichment significantly increased the neuronal cell numbers in the hippocampus, and promoted cell proliferation and neurogenesis in the olfactory bulb. In contrast, the glial cell numbers remained unchanged in both of the regions. Our results suggest that exposure to novel odor stimuli promotes hippocampal neurogenesis and support the idea that enriched environments may delay the onset or slow down the progression of neurodegenerative disorders.
Alzheimer Disease ; Animals ; Atrophy ; Brain ; Cell Count ; Cell Proliferation ; Hippocampus ; Memory ; Methods ; Mice* ; Neural Pathways ; Neurodegenerative Diseases ; Neurogenesis ; Neuroglia ; Neurons* ; Odors* ; Olfactory Bulb