title: Changes in total cell numbers of the basal ganglia in patients with multiple system atrophy - A stereological study.
abstract: Total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the basal ganglia and red nucleus were estimated in brains from 11 patients with multiple system atrophy (MSA) and 11 age- and gender-matched control subjects with unbiased stereological methods. Compared to the control subjects, the MSA patients had a substantially lower number of neurons in the substantia nigra (p=0.001), putamen (p=0.001), and globus pallidus (p<0.001), and, to a lesser extent in the caudate nucleus (p=0.03). A significantly lower number of oligodendrocytes were only observed in the putamen (p=0.04) and globus pallidus (p=0.01). In the MSA brains the total number of astrocytes was significantly higher in the putamen (p=0.04) and caudate nucleus (p=0.01). In all examined regions a higher number of microglia were found in the MSA brains with the greatest difference observed in the otherwise unaffected red nucleus (p=0.001). The results from the stereological study were supported by cell marker expression analyses showing increased markers for activated microglia. Our results suggest that microgliosis is a consistent and severe neuropathological feature of MSA, whereas no widespread and substantial loss of oligodendrocytes was observed. We have demonstrated significant neuronal loss in the substantia nigra, striatum, and globus pallidus of patients with MSA, while neurons in other basal ganglia nuclei were spared, supporting the region-specific patterns of neuropathological changes in MSA.
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital, Copenhagen, Denmark; Bispebjerg Movement Disorders Biobank, Bispebjerg University Hospital, Copenhagen, Denmark; Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark. Electronic address: forsklab@bbh.regionh.dk.
authors.forename: Lisette
authors.initials: L
authors.lastname: Salvesen
authors.affiliation: Bispebjerg Movement Disorders Biobank, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Birgitte H
authors.initials: BH
authors.lastname: Ullerup
authors.affiliation: Bispebjerg Movement Disorders Biobank, Bispebjerg University Hospital, Copenhagen, Denmark; Faculty of Medicine, Balikesir University, Balikesir, Turkey.
authors.forename: Fatma B
authors.initials: FB
authors.lastname: Sunay
authors.affiliation: Bispebjerg Movement Disorders Biobank, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brudek
authors.affiliation: Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Annemette
authors.initials: A
authors.lastname: Løkkegaard
authors.affiliation: Department of Pathology, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Tina K
authors.initials: TK
authors.lastname: Agander
authors.affiliation: Bispebjerg Movement Disorders Biobank, Bispebjerg University Hospital, Copenhagen, Denmark; Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Winge
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Pakkenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D060888:Real-Time Polymerase Chain Reaction; D012012:Red Nucleus / Q000378:metabolism / Q000473:pathology*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D020531:Subthalamic Nucleus / Q000378:metabolism / Q000473:pathology*
keywords: Basal ganglia; Glial cells; Multiple system atrophy; Neuronal loss; Red nucleus; Stereology