All events

Deciphering non-neuronal cells fate in Alzheimer’s disease by next generation transcriptomics

Lecture
Date:
Monday, June 20, 2022
Hour: 11:30 - 12:30
Location:
Mor Kenigsbuch
|
Advisors: Prof. Michal Schwartz & Prof. Ido Amit

For decades, Alzheimer's disease (AD) was perceived as a disease of the neuron alone. However, research advances in recent years have challenged this concept and shed light on the critical roles of other cells within the central nervous system (CNS) and the periphery. Within the CNS, microglia and astrocytes were revealed to be key players in disease progression, while other cell types, such as oligodendrocytes, pericytes, and endothelial cells, remained relatively understudied. In my PhD, I focused on understanding how two non-neuronal cell types, the oligodendroglia in the brain parenchyma and the choroid plexus (CP) epithelium, respond to AD and how they possibly affect pathological processes. My research identified a cellular state of oligodendrocytes that significantly increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). Oligodendrocytes with DOL signature could also be identified in a mouse model of tauopathy and other neurodegenerative and autoimmune inflammatory conditions, suggesting a common response of oligodendrocytes to severe deviation from homeostasis. In the second part of my PhD, I contributed to a research aiming to investigate the mechanisms underlying the decline of the CP's neuroprotective abilities in the context of AD. We found that exposure of choroid plexus epithelial cultures to 24-hydroxycholesterol (24-OH), the enzymatic product of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), results in downregulation of aging- related transcriptomic signatures-such as Interferon type I (IFN-I) associated inflammation. Moreover, we found that CYP46A1 is constitutively expressed by the CP of humans and mice but is reduced in AD patients and 5xFAD mice. Overexpression of Cyp46a1 at the CP in 5xFAD mice attenuated cognitive loss and brain inflammation. Our results suggest that CP CYP46A1 is an unexpected safeguard against chronic anti-viral-like responses that can be rescued when lost. Overall, my PhD work highlights the significance of studying the fate of non-neuronal cell types in neurodegenerative diseases, in general, and in AD, in particular, and emphasizes the potential of next- generation transcriptomic techniques as a powerful tool to unveil previously unexpected pathways and mechanisms involved in these diseases.  Zoom link-https://weizmann.zoom.us/j/98815291638?pwd=cnZTanhzWkEyYmh4Mjk4OWxHMGE5UT09 Meeting ID:988 1529 1638 Password:880170

Sugar: A gut choice

Lecture
Date:
Tuesday, June 21, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Diego V. Bohórquez, Ph.D.
|
Departments of Medicine and Neurobiology Duke University, Durham, NC

Animals distinguish sugars from non-nutritive sweeteners even in the absence of sweet taste. This hidden sugar sense seems to reside in the gut, but the cells and neural circuits are unknown. In 2018, the Bohórquez Laboratory discovered a neural circuit linking the gut to the brain in one synapse. The neural circuit is formed between neuropod cells in the gut and the vagus nerve. This neural circuit is essential to convey sensory cues from sugars. In 2020, the Bohórquez Laboratory discovered using a new fiber optic technology along with optogenetics, that animals rely on neuropod cells to distinguish sugars from non-caloric sweeteners. Much like the brain relies on retinal cone cells to see color, gut neuropod cells help the brain’s choose sugar over non-caloric sweeteners.

Genetic Factors & Long Range Circuit Dynamics Underlying Memory Processing-ZOOM

Lecture
Date:
Tuesday, June 28, 2022
Hour: 15:00 - 16:00
Location:
Prof. Priya Rajasethupathy
|
Lab of Neural Dynamics and Cognition Rockefeller University NY

How do fleeting molecules and dynamic neural codes enable the conversion of transient stimuli into lasting internal representations? And are there unique strategies to achieve memory on different time scales. Our lab addresses these questions by bridging functional genomics with systems neuroscience to provide cross-disciplinary insights. On one hand, we perform genetic mapping in outbred mice for unbiased discovery of genes, cell types, and circuits relevant for memory across different time scales. In parallel, we develop and apply methodologies to record and manipulate high resolution neural activity from these relevant circuits in the behaving animal. In today’s talk, I will discuss how these approaches have led to new insights into the genetic contributions and long-range circuit dynamics that facilitate both short- and long- term memory.  Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

All events

Deciphering non-neuronal cells fate in Alzheimer’s disease by next generation transcriptomics

Lecture
Date:
Monday, June 20, 2022
Hour: 11:30 - 12:30
Location:
Mor Kenigsbuch
|
Advisors: Prof. Michal Schwartz & Prof. Ido Amit

For decades, Alzheimer's disease (AD) was perceived as a disease of the neuron alone. However, research advances in recent years have challenged this concept and shed light on the critical roles of other cells within the central nervous system (CNS) and the periphery. Within the CNS, microglia and astrocytes were revealed to be key players in disease progression, while other cell types, such as oligodendrocytes, pericytes, and endothelial cells, remained relatively understudied. In my PhD, I focused on understanding how two non-neuronal cell types, the oligodendroglia in the brain parenchyma and the choroid plexus (CP) epithelium, respond to AD and how they possibly affect pathological processes. My research identified a cellular state of oligodendrocytes that significantly increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). Oligodendrocytes with DOL signature could also be identified in a mouse model of tauopathy and other neurodegenerative and autoimmune inflammatory conditions, suggesting a common response of oligodendrocytes to severe deviation from homeostasis. In the second part of my PhD, I contributed to a research aiming to investigate the mechanisms underlying the decline of the CP's neuroprotective abilities in the context of AD. We found that exposure of choroid plexus epithelial cultures to 24-hydroxycholesterol (24-OH), the enzymatic product of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), results in downregulation of aging- related transcriptomic signatures-such as Interferon type I (IFN-I) associated inflammation. Moreover, we found that CYP46A1 is constitutively expressed by the CP of humans and mice but is reduced in AD patients and 5xFAD mice. Overexpression of Cyp46a1 at the CP in 5xFAD mice attenuated cognitive loss and brain inflammation. Our results suggest that CP CYP46A1 is an unexpected safeguard against chronic anti-viral-like responses that can be rescued when lost. Overall, my PhD work highlights the significance of studying the fate of non-neuronal cell types in neurodegenerative diseases, in general, and in AD, in particular, and emphasizes the potential of next- generation transcriptomic techniques as a powerful tool to unveil previously unexpected pathways and mechanisms involved in these diseases.  Zoom link-https://weizmann.zoom.us/j/98815291638?pwd=cnZTanhzWkEyYmh4Mjk4OWxHMGE5UT09 Meeting ID:988 1529 1638 Password:880170

Sugar: A gut choice

Lecture
Date:
Tuesday, June 21, 2022
Hour: 12:30 - 13:30
Location:
Gerhard M.J. Schmidt Lecture Hall
Diego V. Bohórquez, Ph.D.
|
Departments of Medicine and Neurobiology Duke University, Durham, NC

Animals distinguish sugars from non-nutritive sweeteners even in the absence of sweet taste. This hidden sugar sense seems to reside in the gut, but the cells and neural circuits are unknown. In 2018, the Bohórquez Laboratory discovered a neural circuit linking the gut to the brain in one synapse. The neural circuit is formed between neuropod cells in the gut and the vagus nerve. This neural circuit is essential to convey sensory cues from sugars. In 2020, the Bohórquez Laboratory discovered using a new fiber optic technology along with optogenetics, that animals rely on neuropod cells to distinguish sugars from non-caloric sweeteners. Much like the brain relies on retinal cone cells to see color, gut neuropod cells help the brain’s choose sugar over non-caloric sweeteners.

Genetic Factors & Long Range Circuit Dynamics Underlying Memory Processing-ZOOM

Lecture
Date:
Tuesday, June 28, 2022
Hour: 15:00 - 16:00
Location:
Prof. Priya Rajasethupathy
|
Lab of Neural Dynamics and Cognition Rockefeller University NY

How do fleeting molecules and dynamic neural codes enable the conversion of transient stimuli into lasting internal representations? And are there unique strategies to achieve memory on different time scales. Our lab addresses these questions by bridging functional genomics with systems neuroscience to provide cross-disciplinary insights. On one hand, we perform genetic mapping in outbred mice for unbiased discovery of genes, cell types, and circuits relevant for memory across different time scales. In parallel, we develop and apply methodologies to record and manipulate high resolution neural activity from these relevant circuits in the behaving animal. In today’s talk, I will discuss how these approaches have led to new insights into the genetic contributions and long-range circuit dynamics that facilitate both short- and long- term memory.  Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

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