Dataset Information

JNK3 Overexpression in the Entorhinal Cortex Impacts on the Hippocampus and Induces Cognitive Deficiencies and Tau Misfolding.

ABSTRACT: c-Jun N-terminal kinases (JNKs) are a family of protein kinases activated by a myriad of stimuli consequently modulating a vast range of biological processes. In human postmortem brain samples affected with Alzheimer's disease (AD), JNK overactivation has been described; however, its role in AD onset and progression is still under debate. One of the earliest affected areas in the pathology is the entorhinal cortex (EC). Noteworthy, the deterioration of the projection from EC to hippocampus (Hp) point toward the idea that the connection between EC and Hp is lost in AD. Thus, the main objective of the present work is to address if JNK3 overexpression in the EC could impact on the hippocampus, inducing cognitive deficits. Data obtained in the present work suggest that JNK3 overexpression in the EC influences the Hp leading to cognitive impairment. Moreover, proinflammatory cytokine expression and Tau immunoreactivity were increased both in the EC and in the Hp. Therefore, activation of inflammatory signaling and induction of Tau aberrant misfolding caused by JNK3 could be responsible for the observed cognitive impairment. Altogether, JNK3 overexpression in the EC may impact on the Hp inducing cognitive dysfunction and underlie the alterations observed in AD.

SUBMITTER: Ardanaz CG

PROVIDER: S-EPMC10251484 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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JNK3 Overexpression in the Entorhinal Cortex Impacts on the Hippocampus and Induces Cognitive Deficiencies and Tau Misfolding.

Ardanaz Carlos G CG Ezkurdia Amaia A Bejarano Arantza A Echarte Beatriz B Smerdou Cristian C Martisova Eva E Martínez-Valbuena Iván I Luquin María-Rosario MR Ramírez María J MJ Solas Maite M

ACS chemical neuroscience 20230526 11

c-Jun N-terminal kinases (JNKs) are a family of protein kinases activated by a myriad of stimuli consequently modulating a vast range of biological processes. In human postmortem brain samples affected with Alzheimer's disease (AD), JNK overactivation has been described; however, its role in AD onset and progression is still under debate. One of the earliest affected areas in the pathology is the entorhinal cortex (EC). Noteworthy, the deterioration of the projection from EC to hippocampus (Hp) ...[more]

PMID: 37236204

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Project description:Neural computation is associated with the emergence, reconfiguration, and dissolution of cell assemblies in the context of varying oscillatory states. Here, we describe the complex spatiotemporal dynamics of cell assemblies through temporal network formalism. We use a sliding window approach to extract sequences of networks of information sharing among single units in hippocampus and entorhinal cortex during anesthesia and study how global and node-wise functional connectivity properties evolve through time and as a function of changing global brain state (theta vs. slow-wave oscillations). First, we find that information sharing networks display, at any time, a core-periphery structure in which an integrated core of more tightly functionally interconnected units links to more loosely connected network leaves. However the units participating to the core or to the periphery substantially change across time windows, with units entering and leaving the core in a smooth way. Second, we find that discrete network states can be defined on top of this continuously ongoing liquid core-periphery reorganization. Switching between network states results in a more abrupt modification of the units belonging to the core and is only loosely linked to transitions between global oscillatory states. Third, we characterize different styles of temporal connectivity that cells can exhibit within each state of the sharing network. While inhibitory cells tend to be central, we show that, otherwise, anatomical localization only poorly influences the patterns of temporal connectivity of the different cells. Furthermore, cells can change temporal connectivity style when the network changes state. Altogether, these findings reveal that the sharing of information mediated by the intrinsic dynamics of hippocampal and entorhinal cortex cell assemblies have a rich spatiotemporal structure, which could not have been identified by more conventional time- or state-averaged analyses of functional connectivity.

Dataset Information

JNK3 Overexpression in the Entorhinal Cortex Impacts on the Hippocampus and Induces Cognitive Deficiencies and Tau Misfolding.

Publications

JNK3 Overexpression in the Entorhinal Cortex Impacts on the Hippocampus and Induces Cognitive Deficiencies and Tau Misfolding.

Similar Datasets

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