Amira Latif-Hernandez (United States of America)
Stanford University
Neurology and Neurological Sciences
Amira obtained her Ph.D. in Neuroscience from the KU Leuven, Belgium, in the summer of 2017. One of the most gratifying contributions of her doctoral studies was the development of a new electrophysiology tool to assess synaptopathies and the establishment of long-term synaptic plasticity from prefrontal cortex slices to characterize the pathophysiology of novel mouse models of Alzheimer’s disease. In Autumn of 2017, she moved to the Longo laboratory at the Stanford School of Medicine. During 3 years of post-doctoral work, she independently established a multi-electrode array system that allows high-throughput analyses of multiple long-lasting forms of synaptic plasticity. Her projects involve neuronal plasticity, RNA-sequencing, molecular biochemistry, signaling mechanisms, target validation and drug development strategies for Alzheimer’s disease with the objective of investigating neurotrophin receptor signaling pathways that contribute to synaptic degeneration and preservation. In October 2020, Amira was appointed Instructor of Neurodegenerative Disease Research at Stanford Neurology, to help develop improved and more powerful approaches that will better reveal key synaptic mechanisms and candidate modules associated with neuroplasticity and affected in AD mouse models, by identifying activity-dependent gene expression signatures that will ultimately serve as a platform for potential therapeutics and animal to human translation. When Amira is not dedicated to science, she truly enjoys running, hiking, dancing, cycling, boxing, cooking, reading books, writing journals, and, when possible, camping, surfing and climbing.

Presenter of 1 Presentation

 Conference Calendar

NEURONAL AND GLIAL ACTIVITY-DEPENDENT GENE CO-EXPRESSION NETWORKS IN TAUOPATHY MICE ARE NORMALIZED BY IN VIVO MODULATION OF P75NTR SIGNALING

Session Name
1750 - COINCIDENT NEURODEGENERATIVE DISEASE, AMYLOID, TAU , TDP-43 PATHOLOGY (ID 192)
Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE: 114
Lecture Time
05:15 PM - 05:30 PM
Presenter

Abstract

Aims

Modulating p75NTR signaling with the small molecule LM11A-31 (C31) was previously shown to prevent synaptic dysfunction, as assessed with long-term potentiation (LTP), in a mouse model of tauopathy (PS19). We ask whether tauopathy-related alterations in gene co-expression, in response to stimulation, can be normalized by C31.

Methods

Wildtype (WT) and PS19 mice were treated with vehicle or C31 for 3 months starting at 6 months of age. Theta burst stimulation (TBS) was used to induce late-phase LTP. Bulk RNA sequencing with cell-type enrichment analysis was performed on unstimulated and stimulated slices to generate activity-dependent profiles of gene co-expression networks using weighted analysis with a soft-threshold power of 18 to achieve scale-free topology R2>0.8 and module size 25.

Results

In PS19 versus WT mice, 16 activity-dependent modules were significantly down-regulated with cell-type enrichment for neurons and 8 were up-regulated with enrichment for glia. Notably, all of the transcriptional co-expression modules altered in PS19 mice were normalized to WT level with C31. Down-regulation of gene transcription modules in PS19 mice, known to be significantly enriched for genes in neurons associated to post-synapse and LTP, were up-regulated upon C31 treatment; while in microglial-, oligodendrogial- and astroglial-associated modules, up-regulated genes in PS19 mice were downregulated with C31. Comparison of mouse and human modules demonstrated that those affected in treated mice have similar up- and down-regulated pattern of expression in human AD.

Conclusions

We identified neuronal and glial mechanisms by which the p75NTR-modulator C31 might prevent tauopathy-associated synaptic dysfunction and

figure 1. co-expression module in neurons and microglia ps19-p75-ltp-rna-seq.pngfigure 1 for abstract adpd 2022.jpg
figure 2. mouse-human coexpression ps19-p75-ltp rna-seq.png
underlying alterations of human AD-relevant gene co-expression networks.

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