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Multiple hippocampal processes and cognitive functions change with aging or Alzheimer's disease, but the potential triggers of these aging cascades are not well understood. Here, we quantified hippocampal expression profiles and behavior across the adult lifespan to identify early aging changes and changes that coincide with subsequent onset of cognitive(More)
Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow(More)
Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties(More)
With aging, multiple Ca(2+)-associated electrophysiological processes exhibit increased magnitude in hippocampal pyramidal neurons, including the Ca(2+)-dependent slow afterhyperpolarization (sAHP), L-type voltage-gated Ca(2+) channel (L-VGCC) activity, Ca(2+)-induced Ca(2+) release (CICR) from ryanodine receptors (RyRs), and Ca(2+) transients. This pattern(More)
UNLABELLED Brain Ca2+ regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca2+ -dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca2+ channel activity and(More)
PURPOSE Clinically, perturbations in the semaphorin signaling system have been associated with autism and epilepsy. The semaphorins have been implicated in guidance, migration, differentiation, and synaptic plasticity of neurons. The semaphorin 3F (Sema3F) ligand and its receptor, neuropilin 2 (NPN2) are highly expressed within limbic areas. NPN2 signaling(More)
Age-dependent changes in multiple Ca2+-related electrophysiological processes in the hippocampus appear to be consistent biomarkers of aging, and several also correlate with cognitive decline. These findings have led to the hypothesis that a common mechanism of Ca2+ dyshomeostasis underlies aspects of aging-dependent brain impairment. However, some key(More)
BACKGROUND Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD) with TZDs also has been shown to reduce several well-established brain(More)
It has been recognized for some time that the Ca(2+)-dependent slow afterhyperpolarization (sAHP) is larger in hippocampal neurons of aged compared with young animals. In addition, extensive studies since have shown that other Ca(2+)-mediated electrophysiological responses are increased in hippocampus with aging, including Ca(2+) transients, L-type(More)
Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer's disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between.(More)