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Dissecting the role of Astrocytes in mediating Adult Hippocampal Neurogenesis S&T49

  • School: School of Science and Technology
  • Study mode(s): Full-time / Part-time
  • Starting: 2022
  • Funding: UK student / EU student (non-UK) / International student (non-EU) / Fully-funded

Overview

NTU's Fully-funded PhD Studentship Scheme 2022

Project ID: S&T49

In the subgranular zone of the dentate gyrus, generation of new neurons continues into adulthood. Reductions in this adult hippocampal neurogenesis (AHN) are strongly associated with anxiety, depression and cognitive decline. Further, the rate of AHN is dependent on environment, exercise, and age and is sensitive to insults. Chronic pain and inflammation reduce AHN, while seizures induce a sharp increase, followed by a prolonged reduction. Understanding the mechanisms through which AHN is controlled is critical to a full understanding of affective and cognitive disorders and may offer novel targets for pharmacological interventions.

Astrocytes maintain extracellular homeostasis, including uptake and release of transmitters, ion balance, providing energy substrates, and releasing trophic factors. There is strong evidence for an important role for astrocytes in mediating the rate of AHN. Functional studies, however, are dependent on the availability of the right tools. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) can be targeted to discrete regions of the brain by stereotaxic injection and can now be targeted to astrocytes by using the Glial Fibrillary Acidic Protein (GFAP) promotor. This system can be used to dissect the role of astrocytes in mediating AHN under physiological conditions and in response to insults, such as chronic pain, systemic inflammation, and seizures.

This project will be composed of both in vitro and in vivo experimental approaches. Astrocytes will be targeted with Gq- or Gs- DREADDs to activate or repress activation respectively. In vitro, the release and uptake of gliotransmitters, such as ATP, D-serine and Glutamate in response to either Gq-DREADD or Gs-DREADD activation will be measured in astrocytic cell culture.

The effect of astrocyte-specific Gq-DREADD-activation on AHN will be investigated in vivo in the mouse. DREADDs will be delivered via Adeno-associated virus through stereotaxic injection. Effects on AHN will be assessed through immunohistochemistry (Ki67, Nestin, Doublecortin). BrdU will be used as a tracer to investigate migration, while a green fluorescent protein containing retrovirus will be used to investigate the morphology of the dendritic tree. A similar approach will then be used to assess the contribution of astrocytes to AHN in mouse models of disease, including chronic pain, sterile inflammation and seizures. Behavioural tests will be performed, sensitive for detecting cognitive and affective deficits. The project will dissect the contribution of astrocytes to the regulation of AHN and whether manipulating astrocytes in this region can reverse behavioural phenotypes associated with aberrant AHN in disease models.

School strategic research priority

Entry qualifications

For the eligibility criteria, visit our studentship application page.

How to apply

For guidance and to make an application, please visit our studentship application page. The application deadline is Friday 14 January 2022.

Fees and funding

This is part of NTU's 2022 fully-funded PhD Studentship Scheme.

Guidance and support

Download our full applicant guidance notes for more information.

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