التفاصيل البيبلوغرافية
| العنوان: |
Aging-Dependent Loss of Connectivity in Alzheimer's Model Mice with Rescue by mGluR5 Modulator. |
| المؤلفون: |
Mandino F, Shen X, Desrosiers-Gregoire G, O'Connor D, Mukherjee B, Owens A, Qu A, Onofrey J, Papademetris X, Chakravarty MM, Strittmatter SM, Lake EM |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 08. Date of Electronic Publication: 2024 Jan 08. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD ( App NL-G-F /hMapt ), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment. |
| معلومات مُعتمدة: |
R01 AG034924 United States AG NIA NIH HHS; R01 AG070926 United States AG NIA NIH HHS |
| تواريخ الأحداث: |
Date Created: 20240123 Latest Revision: 20240419 |
| رمز التحديث: |
20240419 |
| مُعرف محوري في PubMed: |
PMC10802481 |
| DOI: |
10.1101/2023.12.15.571715 |
| PMID: |
38260465 |
| قاعدة البيانات: |
MEDLINE |
