CNNE Seminar Series

Date:   Friday, June 4 2021
Time:   12:00PM (noon) – 1:00PM Shenzhen // 2:00PM – 3:00PM Brisbane
Zoom:  https://uqz.zoom.us/j/82677905392

12:00PM SZX / 2:00PM BNE             

Welcome & Introduction by Emeritus Professor Perry Bartlett

12:05PM SZX / 2:05PM BNE             

Presentation – Dr Jing Zhao

Title:  Decreased signalling of EphA4 improves functional performance and motor neuron survival in the SOD1^G93A MND mouse model

Abstract:  Motor Neuron Disease (MND) is an untreatable, progressive, neurodegenerative disease specifically affecting motor neurons. Recently, the tyrosine kinase receptor EphA4 was directly implicated in ALS disease progression. We report that a long-lived mutated form of the EphA4 antagonist EphA4-Fc (mEphA4-Fc), which blocks EphA4 binding to its ligands and inhibits its function, significantly improved functional performance in SOD1^G93A MND model mice, as assessed by rotarod and hind-limb grip strength tests. Further, heterozygous motor neuron-specific EphA4 gene deletion in SOD1^G93A mice promoted significant improvement in functional performance during the disease course and a delay in disease onset relative to control mice. Importantly, mice in the heterozygous deletion group showed significantly improved survival of motor neurons and architecture of endplates of neuromuscular junctions compared with control and homozygous EphA4-deletion groups. Our novel results show that EphA4 signalling directly regulates motor neuron survival and that mEphA4-Fc is a promising therapeutic candidate to slow disease progression in MND. Currently, this mEphA4-Fc has been translated to a Phase 1, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD), First-In-Human Study, aiming to evaluate its safety, tolerability, pharmacokinetics, and efficacy in healthy volunteers and MND patients.

12:25PM SZX / 2:25PM BNE            

Introduction by Professor Pankaj Sah

12:30PM SZX / 2:30PM BNE

Presentation – A/Professor CHEN Xiaojing
Title:  The function of hippocampal dentate gyrus and its role on the downstream hippocampal region

Abstract:  The hippocampus is the core brain region of memory and the residence of “cognitive map”. Cognitive map theory suggests that, the spatial framework created by the hippocampus could organize and interrelate the items and events of experience, and support the flexible behavior of the animals (O’Keefe & Nadel, 1978). Dentate gyrus is the first step of information transfer into the hippocampus. It has the most complex neural circuit including different cell types. Memory interference is a common cause of forgetting. Theoretical models have predicted a crucial role for dentate gyrus in pattern separation, a process that reduces overlap and enhances dissimilarity between representations and thus avoid memory interference. My work revealed the different functions of various dentate principal cell types in spatial memory. By using a mouse line lacking dentate gyrus, we examined the function of DG on its downstream brain region, the CA1 subfield of the hippocampus. We found DG is necessary for the CA1 neurons to accurately represent spatial locations and movement directions.

12:45PM SZX / 2:45PM BNE             Q&A session and discussion

1:00PM SZX / 3:00PM BNE               Seminar concludes