Investigative Studies into mTORC1-Dependent Dendritic Branch Potentiation in TSC

Abstract

Many patients with TSC have long-term memory impairment. Yet, the underlying mechanism leading to cognitive deficits is not well understood. Memories are stored at clusters of synapses, within a dendritic branch, and requires the protein composition of that branch to be remodeled to strengthen communication. In the proposed studies, we will specifically test the hypothesis that in preclinical models of TSC branch potentiation is reduced. Indeed, calcium imaging of neurons isolated from WT, TSC1 KO, andTSC1 heterozyotic (Het) mice reveals a dose-dependent loss of branch potentiation. We are investigating the underlying molecular mechanism leading to deficits in branch-specific potentiation in TSC. We found that several mRNAs that code for ion channels are predicted to be regulated by the microRNA miR-129-5p. These ion channels are overexpressed and mislocalized in TSC null dendrites and include Kv1.1, CaV2.2, and 21.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2022
Accession Number
AD1193695

Entities

People

  • Kimberly F Raab-Graham

Organizations

  • Wake Forest University

Tags

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Autism
  • Biochemistry
  • Biomedical Research
  • Covid-19
  • Department Of Defense
  • Diseases
  • Electronic Mail
  • Electrophysiology
  • Health
  • Management Personnel
  • Maryland
  • Medical Personnel
  • Membrane Potentials
  • North Carolina
  • Organizational Structure
  • Proteins
  • Students
  • Supply Chain
  • Universities

Fields of Study

  • Biology

Readers

  • Military Logistics and Supply Chain Management
  • Molecular Biology and Genetics
  • Neural Network Machine Learning.