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- 01HNWQGYH2D506S9HY69VMJNRY classification C3.
- 01HNWQGYH2D506S9HY69VMJNRY date "2022".
- 01HNWQGYH2D506S9HY69VMJNRY language "eng".
- 01HNWQGYH2D506S9HY69VMJNRY type conference.
- 01HNWQGYH2D506S9HY69VMJNRY subject "Biology and Life Sciences".
- 01HNWQGYH2D506S9HY69VMJNRY subject "Medicine and Health Sciences".
- 01HNWQGYH2D506S9HY69VMJNRY issn "1748-1708".
- 01HNWQGYH2D506S9HY69VMJNRY issn "1748-1716".
- 01HNWQGYH2D506S9HY69VMJNRY issue "Supplement 725".
- 01HNWQGYH2D506S9HY69VMJNRY presentedAt urn:uuid:50f4e48a-3127-4833-8bc3-a7f8dd8fca5a.
- 01HNWQGYH2D506S9HY69VMJNRY volume "236".
- 01HNWQGYH2D506S9HY69VMJNRY abstract "Introduction Alzheimer’s disease (AD) is an untreatable neurodegenerative disorder, the underlying cause(s) of which remain unknown. Recent research by us and others supports the so-called 'calcium hypothesis of AD', which posits that the disruption/dysregulation of neuronal intracellular calcium regulation may be one of the initiators of AD pathology. To date however, most of these studies have been conducted using animal models of AD. As such, it remains unclear if these findings of neuronal calcium homeostatic dysregulation are replicated in human brain tissue carrying specific AD-linked mutations due to the paucity of living human brain tissue available for research. Therefore, the aim of the current study was to determine if previous work in our lab, which demonstrated that intracellular calcium regulation was disrupted in primary hippocampal neurons from a transgenic mouse model of AD (3xTgAD mouse) [1], was replicated in human induced pluripotent stem cell (IPSC)-derived neural progenitor cells (NPCs) containing a familial AD mutation of the presenilin 1 protein (M139V), and a healthy donor control (CaCntrl). Methods NPCs were induced by dual inhibition of TGF-β/BMP-dependent SMAD signalling in culture and characterised by immunostaining for SOX2 andβIII tubulin presence. Thereafter, NPC calcium imaging was conducted by loading the cells with a calcium-sensitive dye (Calbryte™ 520 AM; 4μM) for 1 hour and then placing them in a perfusion chamber continuously superperfused with HBSS. Intracellular calcium([Ca2+]i) responses to 50mM K+ extracellular HBSS and the Ca2+ionophore, ionomycin (10μM), were recorded using WinFluor software (J. Dempster, University of Strathclyde). Data are expressed as mean±S.E.M. N values are displayed as n = x cells, x experiments. All results presented were analysed by two-tailed Welch’s t test. Results We initially found that basal [Ca2+]i levels in the M139V NPCs were significantly elevated relative to CaCntrl (14.4±1.2 arbitrary units vs7.7±0.4 arbitrary units; p<0.0001). Furthermore, we found that the ΔF/F relative percentage change of K+-evoked [Ca2+]i signals (relative to baseline) was significantly greater in M139V NPCs relative to CaCntrl ( 732.1%±77.6 (n = 64, 5) vs104.3%±9.2, (n = 56, 4); p<0.0001). Similarly, the ΔF/F of ionomycin-evoked [Ca2+]i signals was also significantly greater in M139V NPCs compared to CaCntrl (431.5%±42.0 vs184.4%±10.6;p<0.0001). Conclusion Our results indicate that, similar to our previous work using primary cultured hippocampal mouse neurons, both basal and evoked [Ca2+]i levels in presenilin mutant cells are significantly heightened relative to controls. The profound differences in calcium responses observed in neural stem cell populations prior to maturation supports the suggestion that AD pathogenesis commences before more overt, neurohistopathological changes. References [1]Kaar, A, 2019, ‘Investigating neuronal calcium homeostasis in murine models of Alzheimer’s disease.' PhD Thesis, University College Cork".
- 01HNWQGYH2D506S9HY69VMJNRY author 49d1612f-a672-11ed-ac27-dc37b5792249.
- 01HNWQGYH2D506S9HY69VMJNRY author urn:uuid:07935597-4ba0-4b5c-8036-486008ad0407.
- 01HNWQGYH2D506S9HY69VMJNRY author urn:uuid:2f8709ff-110c-4151-a92f-a5b3a88facec.
- 01HNWQGYH2D506S9HY69VMJNRY author urn:uuid:a38a43f0-2433-4e06-852f-316d58bde486.
- 01HNWQGYH2D506S9HY69VMJNRY dateCreated "2024-02-05T13:32:35Z".
- 01HNWQGYH2D506S9HY69VMJNRY dateModified "2024-09-13T13:58:43Z".
- 01HNWQGYH2D506S9HY69VMJNRY name "Altered calcium homeostasis in induced pluripotent stem cell-derived human neural progenitor cells containing familial presenilin1-linked Alzheimer’s disease mutation, M139V".
- 01HNWQGYH2D506S9HY69VMJNRY pagination urn:uuid:bd5038ca-7882-4a2f-b083-397b2511ae18.
- 01HNWQGYH2D506S9HY69VMJNRY sameAs LU-01HNWQGYH2D506S9HY69VMJNRY.
- 01HNWQGYH2D506S9HY69VMJNRY sourceOrganization urn:uuid:b1fc0ba6-d904-40ff-a4ab-b4cb988c3a45.
- 01HNWQGYH2D506S9HY69VMJNRY type C3.