TY - JOUR
T1 - Age-Related Brain Atrophy and the Positive Effects of Behavioral Enrichment in Middle-Aged Beagles
AU - Noche, Jessica A.
AU - Radhakrishnan, Hamsanandini
AU - Ubele, Margo F.
AU - Boaz, Kathy
AU - Mefford, Jennifer L.
AU - Jones, Erin D.
AU - van Rooyen, Hollie Y.
AU - Perpich, Jessica A.
AU - McCarty, Katie
AU - Meacham, Beverly
AU - Smiley, Jeffrey
AU - Bembenek Bailey, Stasia A.
AU - Puskás, László G.
AU - Powell, David K.
AU - Sordo, Lorena
AU - Phelan, Michael J.
AU - Norris, Christopher M.
AU - Head, Elizabeth
AU - Stark, Craig E.L.
N1 - Publisher Copyright:
© 2024 the authors.
PY - 2024/5/15
Y1 - 2024/5/15
N2 - Aging dogs serve as a valuable preclinical model for Alzheimer’s disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.
AB - Aging dogs serve as a valuable preclinical model for Alzheimer’s disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.
KW - Alzheimer’s disease
KW - Q134R
KW - amyloid
KW - beagle
KW - calcineurin
KW - neurodegeneration
KW - prevention
KW - tacrolimus
UR - http://www.scopus.com/inward/record.url?scp=85193458073&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85193458073&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2366-23.2024
DO - 10.1523/JNEUROSCI.2366-23.2024
M3 - Article
C2 - 38561226
AN - SCOPUS:85193458073
SN - 0270-6474
VL - 44
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 20
M1 - e2366232024
ER -
