Browsing by Subject "Olfactory bulb"

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    Septal contributions to olfactory bulb interneuron diversity in the embryonic mouse telencephalon: role of the homeobox gene Gsx2
    (BMC, 2017-08-16) Qin, Shenyue; Ware, Stephanie M.; Waclaw, Ronald R.; Campbell, Kenneth; Pediatrics, School of Medicine
    Background Olfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence (dLGE) and septum. These cells migrate rostrally toward the OB, where they then radially migrate to populate different OB layers including the granule cell layer (GCL) and the outer glomerular layer (GL). Although previous studies have attempted to investigate regional contributions to OB interneuron diversity, few genetic tools have been used to address this question at embryonic time points when the earliest populations are specified. Methods In this study, we utilized Zic3-lacZ and Gsx2e-CIE transgenic mice as genetic fate-mapping tools to study OB interneuron contributions derived from septum and LGE, respectively. Moreover, to address the regional (i.e. septal) requirements of the homeobox gene Gsx2 for OB interneuron diversity, we conditionally inactivated Gsx2 in the septum, leaving it largely intact in the dLGE, by recombining the Gsx2 floxed allele using Olig2 Cre/+ mice. Results Our fate mapping studies demonstrated that the dLGE and septum gave rise to OB interneuron subtypes differently. Notably, the embryonic septum was found to give rise largely to the calretinin+ (CR+) GL subtype, while the dLGE was more diverse, generating all major GL subpopulations as well as many GCL interneurons. Moreover, Gsx2 conditional mutants (cKOs), with septum but not dLGE recombination, showed impaired generation of CR+ interneurons within the OB GL. These Gsx2 cKOs exhibited reduced proliferation within the septal subventricular zone (SVZ), which correlated well with the reduced number of CR+ interneurons observed. Conclusions Our findings indicate that the septum and LGE contribute differently to OB interneuron diversity. While the dLGE provides a wide range of OB interneuron subtypes, the septum is more restricted in its contribution to the CR+ subtype. Gsx2 is required in septal progenitors for the correct expansion of SVZ progenitors specified toward the CR+ subtype. Finally, the septum has been suggested to be the exclusive source of CR+ interneurons in postnatal studies. Our results here demonstrate that dLGE progenitors in the embryo also contribute to this OB neuronal subtype. Electronic supplementary material The online version of this article (doi:10.1186/s13064-017-0090-5) contains supplementary material, which is available to authorized users.
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    Signatures for Viral Infection and Inflammation in the Proximal Olfactory System in Familial Alzheimer’s Disease
    (Elsevier, 2023) Bubak, Andrew N.; Merle, Laetitia; Niemeyer, Christy S.; Baxter, B. Dnate’; Gentile Polese, Arianna; Ramakrishnan, Vijay; Gomez, Johana; Madrigal, Lucia; Villegas-Lanau, Andres; Lopera, Francisco; Macklin, Wendy; Frietze, Seth; Nagel, Maria A.; Restrepo, Diego; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Alzheimer's disease (AD) is characterized by deficits in olfaction and olfactory pathology preceding diagnosis of dementia. Here we analyzed differential gene and protein expression in the olfactory bulb (OB) and tract (OT) of familial AD (FAD) individuals carrying the autosomal dominant presenilin 1 E280A mutation. Compared to control, FAD OT had increased immunostaining for β-amyloid (Aβ) and CD68 in high and low myelinated regions, as well as increased immunostaining for Iba1 in the high myelinated region. In FAD samples, RNA sequencing showed: (1) viral infection in the OB; (2) inflammation in the OT that carries information via entorhinal cortex from the OB to hippocampus, a brain region essential for learning and memory; and (3) decreased oligodendrocyte deconvolved transcripts. Interestingly, spatial proteomic analysis confirmed altered myelination in the OT of FAD individuals, implying dysfunction of communication between the OB and hippocampus. These findings raise the possibility that viral infection and associated inflammation and dysregulation of myelination of the olfactory system may disrupt hippocampal function, contributing to acceleration of FAD progression.