Role of MEN1 in brain cell connectivity, plasticity and neurodegeneration
| dc.contributor.advisor | Syed, Naweed | |
| dc.contributor.author | Batool, Shadab | |
| dc.contributor.committeemember | Kurrasch, Deborah | |
| dc.contributor.committeemember | Grewal, Savraj | |
| dc.date | 2022-02 | |
| dc.date.accessioned | 2022-01-10T17:44:51Z | |
| dc.date.available | 2022-01-10T17:44:51Z | |
| dc.date.issued | 2022-01 | |
| dc.description.abstract | The precise patterns of neuronal assembly during development determine all functional outputs of a nervous system, ranging from simple reflexes to learning, memory, cognition. To understand how the brain functions normally, as well as how best to repair it after injury, disease or trauma, it is imperative that we first seek to define fundamental steps mediating this neuronal assembly. Moreover, as the brain ages, either the lack of neuronal activity or cell death render synapses dysfunctional, thus giving rise to neurodegenerative disorders. Defining the fundamental mechanisms that underlie precise neuronal assembly during development and regeneration are therefore critical not only for understanding all brain functions, but also for various developmental (e.g., Autism) and neurodegenerative disorders (e.g., Alzheimer’s, Parkinson’s etc.) that are met in clinical practice. A dramatic loss of cholinergic synaptic connections and transmission in the hippocampus is one of the most important neuropathological hallmarks of Alzheimer’s disease. Our lab has identified an interesting mechanism implicating neurotrophic factors more broadly, and the MEN1 (a tumor suppressor) gene, specifically in the expression and synaptic maintenance of nicotinic cholinergic receptors (nAChRs), which are thought to regulate many aspects of synaptic plasticity. Moreover, cholinergic synaptic activity is known to regulate the expression of neurotrophic factors (NTF), and their reduced expression in hippocampus is commonly observed in AD. To determine MEN1’s role in nAChRs receptor expression at the cholinergic synapses, I first investigated the expression patterns of menin, a product of the MEN1 tumor suppressor gene, in the whole murine brain along with other elements of cholinergic synaptic machinery. Here, I present the first direct evidence for the spatiotemporal patterns of menin in neurons and nonneuronal cells throughout development and along with PSD-95, Synaptotagmin and nicotinic acetylcholine receptors (nAChR) specific subunits. These data reveal that menin expression is the highest in certain brain regions involved in cholinergic transmission and in learning and memory. | en_US |
| dc.identifier.citation | Batool, S. (2022). Role of MEN1 in brain cell connectivity, plasticity and neurodegeneration (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/39492 | |
| dc.identifier.uri | http://hdl.handle.net/1880/114270 | |
| dc.language.iso | eng | en_US |
| dc.publisher.faculty | Cumming School of Medicine | en_US |
| dc.publisher.institution | University of Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | en_US |
| dc.subject | synapses | en_US |
| dc.subject | cholinergic | en_US |
| dc.subject | connectivity | en_US |
| dc.subject.classification | Neuroscience | en_US |
| dc.title | Role of MEN1 in brain cell connectivity, plasticity and neurodegeneration | en_US |
| dc.type | doctoral thesis | en_US |
| thesis.degree.discipline | Medicine – Neuroscience | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Doctor of Philosophy (PhD) | en_US |
| ucalgary.item.requestcopy | true | en_US |