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Premature cognitive decline in a mouse model of tuberous sclerosis.
Krummeich, J; Nardi, L; Caliendo, C; Aschauer, D; Engelhardt, V; Arlt, A; Maier, J; Bicker, F; Kwiatkowski, M D; Rolski, K; Vincze, K; Schneider, R; Rumpel, S; Gerber, S; Schmeisser, M J; Schweiger, S.
Afiliación
  • Krummeich J; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Nardi L; Institute of Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Caliendo C; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Aschauer D; Institute of Physiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Engelhardt V; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Arlt A; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Maier J; Institute of Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Bicker F; Institute of Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Kwiatkowski MD; Department of Biochemistry, University of Innsbruck, Innsbruck, Austria.
  • Rolski K; Department of Biochemistry, University of Innsbruck, Innsbruck, Austria.
  • Vincze K; Department of Biochemistry, University of Innsbruck, Innsbruck, Austria.
  • Schneider R; Department of Biochemistry, University of Innsbruck, Innsbruck, Austria.
  • Rumpel S; Institute of Physiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Gerber S; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Schmeisser MJ; Institute of Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Schweiger S; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Aging Cell ; : e14318, 2024 Aug 27.
Article en En | MEDLINE | ID: mdl-39192595
ABSTRACT
Little is known about the influence of (impaired) neurodevelopment on cognitive aging. We here used a mouse model for tuberous sclerosis (TS) carrying a heterozygous deletion of the Tsc2 gene. Loss of Tsc2 function leads to mTOR hyperactivity in mice and patients. In a longitudinal behavioral analysis, we found premature decline of hippocampus-based cognitive functions together with a significant reduction of immediate early gene (IEG) expression. While we did not detect any morphological changes of hippocampal projections and synaptic contacts, molecular markers of neurodegeneration were increased and the mTOR signaling cascade was downregulated in hippocampal synaptosomes. Injection of IGF2, a molecule that induces mTOR signaling, could fully rescue cognitive impairment and IEG expression in aging Tsc2+/- animals. This data suggests that TS is an exhausting disease that causes erosion of the mTOR pathway over time and IGF2 is a promising avenue for treating age-related degeneration in mTORopathies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Aging Cell Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Aging Cell Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido