Neuroscientists identify mechanism for long term memory storage

Date:
March 23, 2022
Source:
University of Iowa Health Care
Summary:
While studying how memories are formed and stored in the brain,
a team identified a novel protein folding mechanism that is
essential for long term memory storage. The researchers further
demonstrated that this mechanism is impaired in a tau-based mouse
model of Alzheimer's disease and that restoring this protein
folding mechanism reverses memory impairment in this mouse model
for the study of dementia.



FULL STORY ==========================================================================
A University of Iowa neuroscience research team has identified a
fundamental biochemical mechanism underlying memory storage and has
linked this mechanism to cognitive deficits in mouse models of Alzheimer's Disease and Related Dementias.


========================================================================== While working to understand how memories are formed and stored in the
brain, the team identified a novel protein folding mechanism in the
endoplasmic reticulum that is essential for long term memory storage. They further demonstrated that this mechanism is impaired in a tau-based mouse
model of Alzheimer's disease and that restoring this protein folding
mechanism reverses memory impairment in this mouse model for the study
of dementia. The findings are published in the March 23 issue of the journalScience Advances.

The team was led by Snehajyoti Chatterjee, PhD, a research associate in
the lab of Ted Abel, PhD, Director of the Iowa Neuroscience Institute and
chair and DEO of the UI Department of Neuroscience and Pharmacology. The
Abel lab has previously shown that the Nr4a family of transcription
factors is essential for long term memory consolidation. This study
identified chaperone proteins in the endoplasmic reticulum, which are
regulated by Nr4a.

"The role of protein folding machinery in long term memory has been
overlooked for decades," Chatterjee says. "We know that gene expression
and protein synthesis are essential for long term memory consolidation
and following learning a large number of proteins are synthesized. For
proteins to be functionally active they need to be folded correctly. Our
work demonstrates the conceptual idea that these chaperone proteins are
the ones that actually fold the proteins to impact synaptic function
and plasticity." The team also used gene therapy to reactivate the
chaperone protein in a mouse model and found that the memory deficit
was reversed, confirming that the protein folding machinery acts as a
molecular switch for memory.

"Identifying this protein folding mechanism is a crucial step toward understanding how memories are stored and what goes wrong in diseases associated with memory impairment," Abel says. "Even though we are
not yet at a point of translating this to patient care, understanding
this pathway is essential to one day being able to prevent and treat neurodegenerative disease." In addition to Chatterjee and Abel,
the research team included Jacob Michaelson, UI associate professor
of psychiatry; postdoctoral scholar Mahesh Shivarama Shetty; graduate
students Ethan Bahl, Utsav Mukherjee, Yann Vanrobaeys, and Emily N. Walsh;
lab assistants Amy L. Yan and Joseph D.

Lederman; and K. Peter Giese of Kings College, London.

The work was supported by NIH grant R01 MH087463, NIH grant K99 AG
068306, Nellie Ball Trust, The Gary & LaDonna Wicklund Research Fund for Cognitive Memory Disorders, The University of Iowa Hawkeye Intellectual
and Developmental Disabilities Research Center, and the Roy J. Carver Charitable Trust.


========================================================================== Story Source: Materials provided by
University_of_Iowa_Health_Care. Original written by Mary Kenyon. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Snehajyoti Chatterjee, Ethan Bahl, Utsav Mukherjee, Emily N. Walsh,
Mahesh Shivarama Shetty, Amy L. Yan, Yann Vanrobaeys, Joseph
D. Lederman, K. Peter Giese, Jacob Michaelson, Ted Abel. Endoplasmic
reticulum chaperone genes encode effectors of long-term
memory. Science Advances, 2022; 8 (12) DOI: 10.1126/sciadv.abm6063 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220323151642.htm

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