Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson’s disease

Abstract

Hyposmia is prodromal, and male sex is a risk marker for an enhanced likelihood ratio of Parkinson’s disease. The literature regarding olfactory bulb volume reduction is controversial, although the olfactory bulb has been largely reported as an early and preferential site for α-synucleinopathy. These pathological deposits have been correlated with neural loss in Nissl-stained material. However, microgliosis has rarely been studied, and astrogliosis has been virtually neglected. In the present report, α-synucleinopathy (α-synuclein), neurodegeneration (Neu-N), astrogliosis (GFAP), and microgliosis (Iba-1) were quantified, using specific markers and stereological methods. Disease, sex, age, disease duration, and post-mortem interval were considered variables for statistical analysis. No volumetric changes have been identified regarding disease or sex. α-Synucleinopathy was present throughout the OB, mainly concentrated on anterior olfactory nucleus. Neurodegeneration (reduction in Neu-N-positive cells) was statistically significant in the diseased group. Astrogliosis (increased GFAP labeling) and microgliosis (increased Iba-1 labeling) were significantly enhanced in the Parkinson’s disease group. When analyzed per sex, neurodegeneration and microgliosis differences are only present in men. These data constitute the demonstration of sex differences in neurodegeneration using specific neural markers, enhanced astrogliosis and increased microgliosis, also linked to male sex, in the human olfactory bulb in Parkinson’s disease.

Tackling the Biological Meaning of the Human Olfactory Bulb Dyshomeostatic Proteome across Neurological Disorders: An Integrative Bioinformatic Approach

“…However, it has been observed that the olfactory loss is dependent on each neurodegenerative disease, ranging from severe (AD, PD, DLB, and mixD) to moderate (frontotemporal dementia) and mild (ALS and PSP). The OB is the first olfactory brain area where neuropathological changes and molecular alterations occur [ 14 , 25 , 26 ], being considered a site for prion-like propagation of pathological misfolded protein aggregates in neurological disorders [ 27 , 28 ]. In this descriptive study, OB proteome datasets were conjointly analyzed to deeply characterize potential common or unique molecular events across seven neurodegenerative diseases (AD, PD, DLB, MixD, FTLD-TDP43, ALS and PSP) that were previously analyzed in an independent manner [ 15 , 16 , 17 , 18 , 19 , 20 ].…”

Trafficking of the glutamate transporter is impaired in LRRK2-related Parkinson’s disease

“…Although impaired glutamate buffering is often found accompanied by astroglial reactivity and neuroinflammation in several disease models [32, 53, 95], conflicting results have been published in the context of PD patients. Enhanced GFAP reactivity has been clearly documented in Substantia Nigra pars compacta (SNpc) and olfactory bulbs [21, 48, 82]. However, one report suggested astrocytic atrophy (instead of reactivity) in PD brains, since low levels of astrocyte markers were observed in the SNpc and the striatum [82], and studies in human iPS-derived astrocytes from PD patients carrying the LRRK2 G2019S mutation suggested a similar mechanism [63].…”

The Human Hippocampus in Parkinson’s Disease: An Integrative Stereological and Proteomic Study

“…One marker is correlated with points for one type of staining (␣-syn), while another marker is used for the remaining tissue (neuropil). The number of points on ␣-syn is divided by the total number of points to obtain the estimated area [37]. Volume was estimated with Cavalieri's probe using Nissl staining (Plan-Neofluar 1x/0.025, Ref.…”

“…Guard zones prevent possible tissue artifacts on the top and bottom surfaces and reduce the section thickness available for counting. The number of cells counted in the study area was divided by the estimated volume of the region [37].…”

“…Several stereological studies have verified atrophy and neurodegeneration in different areas in the postmortem brain of patients with PD [36,37]. Two reports analyzing volumetric changes and neuronal and glial populations in different hippocampal subfields in Giemsa-stained [38] and cresyl violetstained [39] sections concluded that no differences existed between PD and non-Parkinson's disease (NPD) groups [38].…”