Dataset Information

Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.

ABSTRACT: Alzheimer's disease cortical tau pathology initiates in the layer II cell clusters of entorhinal cortex, but it is not known why these specific neurons are so vulnerable. Aging macaques exhibit the same qualitative pattern of tau pathology as humans, including initial pathology in layer II entorhinal cortex clusters, and thus can inform etiological factors driving selective vulnerability. Macaque data have already shown that susceptible neurons in dorsolateral prefrontal cortex express a "signature of flexibility" near glutamate synapses on spines, where cAMP-PKA magnification of calcium signaling opens nearby potassium and hyperpolarization-activated cyclic nucleotide-gated channels to dynamically alter synapse strength. This process is regulated by PDE4A/D, mGluR3, and calbindin, to prevent toxic calcium actions; regulatory actions that are lost with age/inflammation, leading to tau phosphorylation. The current study examined whether a similar "signature of flexibility" expresses in layer II entorhinal cortex, investigating the localization of PDE4D, mGluR3, and HCN1 channels. Results showed a similar pattern to dorsolateral prefrontal cortex, with PDE4D and mGluR3 positioned to regulate internal calcium release near glutamate synapses, and HCN1 channels concentrated on spines. As layer II entorhinal cortex stellate cells do not express calbindin, even when young, they may be particularly vulnerable to magnified calcium actions and ensuing tau pathology.

SUBMITTER: Datta D

PROVIDER: S-EPMC10724870 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.

Datta Dibyadeep D Perone Isabella I Morozov Yury M YM Arellano Jon J Duque Alvaro A Rakic Pasko P van Dyck Christopher H CH Arnsten Amy F T AFT

Cerebral cortex (New York, N.Y. : 1991) 20231201 24

Alzheimer's disease cortical tau pathology initiates in the layer II cell clusters of entorhinal cortex, but it is not known why these specific neurons are so vulnerable. Aging macaques exhibit the same qualitative pattern of tau pathology as humans, including initial pathology in layer II entorhinal cortex clusters, and thus can inform etiological factors driving selective vulnerability. Macaque data have already shown that susceptible neurons in dorsolateral prefrontal cortex express a "signat ...[more]

PMID: 37874022

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Project description:Previous studies of nonhuman primates have found relationships between health and individual differences in personality, behavior, and social status. However, despite knowing these factors are intercorrelated, many studies focus only on a single measure, for example, rank. Consequently, it is difficult to determine the degree to which these individual differences are independently associated with health. The present study sought to untangle the associations between health and these individual differences in rhesus macaques (Macaca mulatta). We studied 85 socially housed macaques at the Oregon and California National Primate Research Centers, and used veterinary records to determine the number of injuries and illnesses for each macaque. We measured personality using 12 items from a well-established primate personality questionnaire, performed focal observations of behaviors, and calculated dominance status from directional supplant data. All twelve personality questionnaire items were reliable and were used to represent five of the six personality dimensions identified in rhesus macaques-Dominance, Confidence, Openness, Anxiety, and Friendliness (also known as Sociability). Following this, we fit generalized linear mixed effects models to understand how these factors were associated with an animal's history of injury and history of illness. In the models, age was an offset, facility was a random effect, and the five personality dimensions, behavior, sex, and dominance status were fixed effects. Number of injuries and illnesses were each best represented by a negative binomial distribution. For the injury models, including the effects did improve model fit. This model revealed that more confident and more anxious macaques experienced fewer injuries. For the illness models, including the fixed effects did not significantly improve model fit over a model without the fixed effects. Future studies may seek to assess mechanisms underlying these associations.

Dataset Information

Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.

Publications

Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.

Similar Datasets

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