PMID- 37446312 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20230718 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 13 DP - 2023 Jul 6 TI - Effects of Voluntary Physical Exercise on the Neurovascular Unit in a Mouse Model of Alzheimer's Disease. LID - 10.3390/ijms241311134 [doi] LID - 11134 AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients. FAU - Andrade-Guerrero, Jesus AU - Andrade-Guerrero J AUID- ORCID: 0000-0002-0574-8814 AD - Laboratorio de Patogenesis Molecular, Laboratorio 4, Edificio A4, Carrera Medico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla 54090, Mexico. AD - Departamento de Neurobiologia del Desarrollo y Neurofisiologia, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro 76230, Mexico. FAU - Orta-Salazar, Erika AU - Orta-Salazar E AD - Departamento de Neurobiologia del Desarrollo y Neurofisiologia, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro 76230, Mexico. FAU - Salinas-Lara, Citlaltepetl AU - Salinas-Lara C AD - Red MEDICI, Carrera Medico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla 54090, Mexico. AD - Departamento de Neuropatologia, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Ciudad de Mexico 14269, Mexico. FAU - Sanchez-Garibay, Carlos AU - Sanchez-Garibay C AUID- ORCID: 0000-0002-0637-5239 AD - Departamento de Neuropatologia, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Ciudad de Mexico 14269, Mexico. FAU - Rodriguez-Hernandez, Luis Daniel AU - Rodriguez-Hernandez LD AD - Laboratorio de Patogenesis Molecular, Laboratorio 4, Edificio A4, Carrera Medico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla 54090, Mexico. AD - Red MEDICI, Carrera Medico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla 54090, Mexico. FAU - Vargas-Rodriguez, Isaac AU - Vargas-Rodriguez I AD - Departamento de Neurobiologia del Desarrollo y Neurofisiologia, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro 76230, Mexico. FAU - Barron-Leon, Nayeli AU - Barron-Leon N AD - Departamento de Neurobiologia del Desarrollo y Neurofisiologia, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro 76230, Mexico. FAU - Ledesma-Alonso, Carlos AU - Ledesma-Alonso C AD - Departamento de Neurobiologia del Desarrollo y Neurofisiologia, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro 76230, Mexico. FAU - Diaz-Cintra, Sofia AU - Diaz-Cintra S AD - Departamento de Neurobiologia del Desarrollo y Neurofisiologia, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro 76230, Mexico. FAU - Soto-Rojas, Luis O AU - Soto-Rojas LO AUID- ORCID: 0000-0002-5013-3608 AD - Laboratorio de Patogenesis Molecular, Laboratorio 4, Edificio A4, Carrera Medico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla 54090, Mexico. AD - Red MEDICI, Carrera Medico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla 54090, Mexico. LA - eng GR - IA202021, IA205423, IN206322/National Autonomous University of Mexico/ GR - 319433/Consejo Nacional de Ciencia y Tecnologia/ PT - Journal Article DEP - 20230706 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Amyloid beta-Peptides) RN - Amyloid angiopathy SB - IM MH - Mice MH - Animals MH - *Alzheimer Disease/metabolism MH - Plaque, Amyloid/metabolism MH - Endothelial Cells/metabolism MH - Mice, Transgenic MH - *Cerebral Amyloid Angiopathy/metabolism MH - Brain/metabolism MH - Disease Models, Animal MH - Amyloid beta-Peptides/metabolism PMC - PMC10342693 OTO - NOTNLM OT - Alzheimer's disease OT - astrocytic end-feet OT - basal membrane OT - cerebral amyloid angiopathy OT - cognition OT - neurovascular unit OT - pericytes OT - physical exercise COIS- The authors declare no conflict of interest. EDAT- 2023/07/14 13:07 MHDA- 2023/07/17 06:42 PMCR- 2023/07/06 CRDT- 2023/07/14 01:16 PHST- 2023/06/17 00:00 [received] PHST- 2023/06/27 00:00 [revised] PHST- 2023/07/03 00:00 [accepted] PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/14 13:07 [pubmed] PHST- 2023/07/14 01:16 [entrez] PHST- 2023/07/06 00:00 [pmc-release] AID - ijms241311134 [pii] AID - ijms-24-11134 [pii] AID - 10.3390/ijms241311134 [doi] PST - epublish SO - Int J Mol Sci. 2023 Jul 6;24(13):11134. doi: 10.3390/ijms241311134.