E Orta-Salazar1, A Aguilar-Vázquez2, H Martínez-Coria3, S Luquín-De Anda4, M Rivera-Cervantes5, C Beas-Zarate5, A Feria-Velasco5, S Díaz-Cintra6. 1. Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, Jal. CP 45110, México; University of CA, Irvine Campus, USA. 2. Instituto de Neurobiología (INB), Campus UNAM-Juriquilla Qro, CP 76230, México. 3. University of CA, Irvine Campus, USA. 4. Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jal. CP 44340, México. 5. Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, Jal. CP 45110, México. 6. Instituto de Neurobiología (INB), Campus UNAM-Juriquilla Qro, CP 76230, México. Electronic address: yoldi@unam.mx.
Abstract
AIMS: The cholinergic system is one of the neurotransmitter systems altered in Alzheimer's disease (AD), the most common form of human dementia. The objective of this work was to determine the REST/NRSF involvement in altered ChAT expression in the neocortex and hippocampus of an AD transgenic mouse (homozygous 3xTg-AD) that over-expresses 3 proteins, amyloid-β precursor protein, presenilin-1, and tau, all of which are associated with AD and cause cellular degeneration. MAIN METHODS: Two groups (WT and 3xTg-AD) of 11-month-old female mice were analyzed and compared. Half of the brains of each group were used for ChAT immunohistochemistry, and Western Blot analyses of ChAT and REST/NRSF were performed on the other half. KEY FINDINGS: We observed significant decreases in the number of ChAT-immunoreactive cells in the Meynert nucleus and of fibers in the frontal motor cortex and hippocampal CA1 area in transgenic mice compared with control mice. An increased level of REST/NRSF protein and a reduction of ChAT protein expression in the 3xTg-AD mice compared with their controls were also found in both in the latter two cerebral regions. SIGNIFICANCE: The increased REST/NRSF expression reported here and its effect on the regulatory region for ChAT transcription could explain the decreased expression of ChAT in the 3xTg-AD mouse; these findings may be associated with the degeneration observed in AD.
AIMS: The cholinergic system is one of the neurotransmitter systems altered in Alzheimer's disease (AD), the most common form of humandementia. The objective of this work was to determine the REST/NRSF involvement in altered ChAT expression in the neocortex and hippocampus of an AD transgenic mouse (homozygous 3xTg-AD) that over-expresses 3 proteins, amyloid-β precursor protein, presenilin-1, and tau, all of which are associated with AD and cause cellular degeneration. MAIN METHODS: Two groups (WT and 3xTg-AD) of 11-month-old female mice were analyzed and compared. Half of the brains of each group were used for ChAT immunohistochemistry, and Western Blot analyses of ChAT and REST/NRSF were performed on the other half. KEY FINDINGS: We observed significant decreases in the number of ChAT-immunoreactive cells in the Meynert nucleus and of fibers in the frontal motor cortex and hippocampal CA1 area in transgenic mice compared with control mice. An increased level of REST/NRSF protein and a reduction of ChAT protein expression in the 3xTg-AD mice compared with their controls were also found in both in the latter two cerebral regions. SIGNIFICANCE: The increased REST/NRSF expression reported here and its effect on the regulatory region for ChAT transcription could explain the decreased expression of ChAT in the 3xTg-AD mouse; these findings may be associated with the degeneration observed in AD.
Authors: Raquel Sanchez-Varo; Marina Mejias-Ortega; Juan Jose Fernandez-Valenzuela; Cristina Nuñez-Diaz; Laura Caceres-Palomo; Laura Vegas-Gomez; Elisabeth Sanchez-Mejias; Laura Trujillo-Estrada; Juan Antonio Garcia-Leon; Ines Moreno-Gonzalez; Marisa Vizuete; Javier Vitorica; David Baglietto-Vargas; Antonia Gutierrez Journal: Int J Mol Sci Date: 2022-05-12 Impact factor: 6.208
Authors: Zoë P Van Acker; Evi Luyckx; Wendy Van Leuven; Eva Geuens; Peter P De Deyn; Debby Van Dam; Sylvia Dewilde Journal: FEBS Lett Date: 2017-05-02 Impact factor: 4.124