Olfactory Dysfunction and Morphological Deficits in ACE2 Knockout Mice

Anantu, S. (2022) Olfactory Dysfunction and Morphological Deficits in ACE2 Knockout Mice. Masters thesis, Indian Institute of Science Education and Research Kolkata.

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Olfactory dysfunctions are a predominant symptom of SARS-CoV-2 infection. While acute inflammation and tissue damage to the olfactory epithelium provide an adequate explanation for deficits during the infection, the aetiology of prolonged symptoms and qualitative disorders is likely to involve more complex mechanisms. ACE2 is ubiquitously expressed in various regions associated with olfaction, although no functional relation has been reported previously. Further, several studies suggest the involvement of ACE2 in the dopaminergic and serotoninergic neuromodulatory systems and adult neurogenesis. These implicate ACE2 downregulation by SARS-CoV-2 as a potential cause of olfactory dysfunctions. In the present study, we characterised the olfactory behaviour and morphological differences in ACE2 knockout mice. A habituation/dishabituation paradigm revealed a deficiency in novel odour discrimination. This was correlated with higher neural activity in the granule cell layer of the olfactory bulb, shown by the expression of c-Fos, a neural activity marker. No difference was seen in the number of dopaminergic neurons in the glomerular layer or in the expression of the marker, tyrosine hydroxylase. Immunoreactivity for MAP2, a neuronal cytoskeletal protein, was found to be reduced in the glomerular layer of ACE2 knockout mice. Reduced expression of MAP2 has previously been linked to sensory deprivation and olfactory learning deficits. Morphometric analyses in the olfactory bulb and nasal cavity showed a decrease in glomerular cross-sectional area and olfactory epithelium thickness. The observations of our study thus provide evidence for olfactory dysfunction and morphological deficits in ACE2 knockout mice, strengthening the plausible involvement of ACE2 in olfaction.

Item Type: Thesis (Masters)
Additional Information: Supervisor: Dr. Nixon M. Abraham, Laboratory of Neural Circuits and Behaviour, Indian Institute of Science Education and Research, Pune; Co-Supervisor: Jayasri Das Sarma
Uncontrolled Keywords: ACE2; ACE2 KO Mice; Coronavirus; Olfactory Dysfunction; Morphological Deficits; SARS-CoV-2
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Department of Biological Sciences
Depositing User: IISER Kolkata Librarian
Date Deposited: 16 Oct 2023 10:40
Last Modified: 16 Oct 2023 10:40
URI: http://eprints.iiserkol.ac.in/id/eprint/1425

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