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PET Quantification in Healthy Humans of Cyclooxygenase-2, a Potential Biomarker of Neuroinflammation.
J Nucl Med
January 2025
Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland;
Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and by inflammogens. This study evaluated the sensitivity of the PET radioligand [C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)--(thiophen-2-ylmethyl)pyrimidin-4-amine ([C]MC1) to detect COX-2 density in a healthy human brain. The specificity of [C]MC1 was confirmed using lipopolysaccharide-injected rats and transgenic mice expressing the human gene, with 120-min baseline and blocked scans using COX-1 and COX-2 selective agents.
View Article and Find Full Text PDFAssociation of Polygenic Risk Score for 5 Diseases With Alzheimer Disease Progression, Biomarkers, and Amyloid Deposition.
Neurology
February 2025
Department of Pharmacology and Toxicology, University of Arizona, Tucson.
Background And Objectives: Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder influenced by genetic and environmental factors. Conditions such as type 2 diabetes (T2D), cardiovascular disease, obesity, depression, and obstructive sleep apnea (OSA) increase AD risk and progression. This study aimed to examine the genetic predisposition to these conditions and their effect on AD pathophysiology, risk, and progression.
View Article and Find Full Text PDFEnsemble priming via competitive inhibition: local mechanisms of sensory context storage and deviance detection in the neocortical column.
bioRxiv
January 2025
Department of Neuroscience, Brown University, Providence, RI, USA.
The process by which neocortical neurons and circuits amplify their response to an unexpected change in stimulus, often referred to as deviance detection (DD), has long been thought to be the product of specialized cell types and/or routing between mesoscopic brain areas. Here, we explore a different theory, whereby DD emerges from local network-level interactions within a neocortical column. We propose that deviance-driven neural dynamics can emerge through interactions between ensembles of neurons that have a fundamental inhibitory motif: competitive inhibition between reciprocally connected ensembles under modulation from feed-forward selective (dis)inhibition.
View Article and Find Full Text PDFCommon neocortical and hippocampal correlates of Performance errors in a timing task.
J Neurosci
January 2025
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102.
We aimed to identify the neuronal correlates of performance errors in a difficult timing task. Male rats were trained to seek ewards and avoid hocks depending on the position of photic conditioned stimuli (CS- and CS-, respectively). Then, they were exposed to conflict trials where they had to time the interval between the CS-R and CS-S to obtain rewards while avoiding footshocks.
View Article and Find Full Text PDFCerebral cortical functional hyperconnectivity in a mouse model of spinocerebellar ataxia type 8 (SCA8).
Neurobiol Dis
January 2025
Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
Spinocerebellar Ataxia Type 8 (SCA8) is an inherited neurodegenerative disease caused by a bidirectionally expressed CTG•CAG expansion mutation in the ATXN8 and ATXN8OS genes. While SCA8 patients have motor abnormalities, patients may also exhibit psychiatric symptoms and cognitive dysfunction. It is difficult to elucidate how the disease alters brain function in areas with little or no degeneration producing both motor and cognitive symptoms.
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