Caloric restriction prevents aging-associated changes in spike-mediated Ca2+ accumulation and the slow afterhyperpolarization in hippocampal CA1 pyramidal neurons

Hemond, Peter J.; Jaffe, David B.

doi:10.1016/j.neuroscience.2005.05.044

Cited by 41 publications

(35 citation statements)

References 56 publications

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“…3C), but we have found an age-related reduction in HVA current inactivation and an increase in low-voltage-activated (LVA; T-type) currents (Han et al 2005;Griffith 1995, 1996;Murchison et al 2004). Furthermore, unlike cholinergic BF neurons, Ca 2ϩ buffering does not seem to be increased and may even be reduced with age in hippocampal CA1 neurons, given that Ca 2ϩ transients are increased in amplitude (Gant et al 2006;Hemond and Jaffe 2005;Thibault et al 2001) and addition of exogenous Ca 2ϩ buffers reverses hippocampal dysfunction and cognitive deficits (Ouanounou et al 1999;Tonkikh et al 2006). This reduced or unchanged Ca 2ϩ buffering and increased L-type Ca 2ϩ channel activity is believed to partially underlie an enhanced sAHP with age in CA1 neurons (Landfield and Pitler 1984;Power et al 2002) that alters the firing properties of these cells and contributes to cognitive impairment (reviewed in Disterhoft and Oh 2007).…”

Section: Comparative Agingmentioning

confidence: 81%

“…This is the first study to link a physiological property of individual cholinergic BF neurons to age-related cognitive impairment in the ability of rats to learn the Morris water-maze task. Previously in rat BF, cholinergic cell size and number, levels of nerve growth factor, and mRNA expression have been linked to impaired performance of this task (Fischer et al 1991(Fischer et al , 1992Higgins et al 1990;Sugaya et al 1998).…”

Section: Behavioral Resultsmentioning

confidence: 99%

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Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

Murchison

McDermott

LaSarge

et al. 2009

Journal of Neurophysiology

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Murchison D, McDermott AN, LaSarge CL, Peebles KA, Bizon JL, Griffith WH. Enhanced calcium buffering in F344 rat cholinergic basal forebrain neurons is associated with age-related cognitive impairment. J Neurophysiol 102: 2194 -2207, 2009. First published August 12, 2009 doi:10.1152/jn.00301.2009. Alterations in neuronal Ca 2ϩ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca 2ϩ influx, buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca 2ϩ current recording with Ca 2ϩ -sensitive ratiometric microfluorimetry to measure Ca 2ϩ buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age-or cognitionrelated changes in the amplitudes or fractional compositions of the whole cell Ca 2ϩ channel currents. However, Ca 2ϩ buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca 2ϩ buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca 2ϩ buffering by cholinergic basal forebrain neurons may be important during aging.

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Section: Comparative Agingmentioning

confidence: 81%

Section: Behavioral Resultsmentioning

confidence: 99%

Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

Murchison

McDermott

LaSarge

et al. 2009

Journal of Neurophysiology

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“…Furthermore, alterations in a number of Ca 2ϩ -dependent/mediated processes have been found to be consistent biomarkers of aging in hippocampal neurons, including those in the Ca 2ϩ -dependent slow afterhyperpolarization (sAHP), spike accommodation, the Ca 2ϩ action potential, and whole-cell Ca 2ϩ currents (Landfield and Pitler, 1984;Disterhoft et al, 1996;Norris et al, 1998;Thibault et al, 1998;Disterhoft et al, 2004;Tombaugh et al, 2005). The activity of L-type voltage-gated Ca 2ϩ channels (Thibault and Landfield, 1996) and the rise of [Ca 2ϩ ] i during postsynaptic action potential generation (Thibault et al, 2001;Hemond and Jaffe, 2005) are also increased in hippocampal neurons from aging animals. These and other findings, from different neuronal cell types and technical approaches, have given rise to several versions of the general hypothesis that a common mechanism of Ca 2ϩ dysregulation underlies many aspects of functional aging and, potentially, Alzheimer's disease (AD) (Landfield and Pitler, 1984;Gibson and Peterson, 1987;Landfield, 1987;Khachaturian, 1989;Disterhoft et al, 1996;Michaelis et al, 1996;Thibault et al, 1998;Verkhratsky and Toescu, 1998;Murchison et al, 2004;.…”

Section: Introductionmentioning

confidence: 99%

Early and Simultaneous Emergence of Multiple Hippocampal Biomarkers of Aging Is Mediated by Ca²⁺-Induced Ca²⁺Release

Gant¹,

Sama²,

Landfield³

et al. 2006

J. Neurosci.

173

181

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Age-dependent changes in multiple Ca2ϩ -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 Ca 2ϩ dyshomeostasis underlies aspects of aging-dependent brain impairment. However, some key predictions of this view remain untested, including that multiple Ca 2ϩ -related biomarkers should emerge concurrently during aging and their onset should also precede/coincide with initial signs of cognitive decline. Moreover, blocking a putative common source of dysregulated Ca 2ϩ should eliminate aging differences. Here, we tested these predictions using combined electrophysiological, imaging, and pharmacological approaches in CA1 neurons to determine the ages of onset (across 4-, 10-, 12-, 14-, and 23-month-old F344 rats) of several established biomarkers, including the increases in the slow afterhyperpolarization, spike accommodation, and [Ca 2ϩ ] i rise during repetitive synaptic stimulation. In addition, we tested the hypothesis that altered Ca 2ϩ -induced Ca 2ϩ release (CICR) from ryanodine receptors, which can be triggered by L-type Ca 2ϩ channels, provides a common source of dysregulated Ca 2ϩ in aging. Results showed that multiple aging biomarkers were first detectable at about the same age (12 months of age; approximately midlife), sufficiently early to influence initial cognitive decline. Furthermore, selectively blocking CICR with ryanodine slowed the Ca 2ϩ rise during synaptic stimulation more in aged rat neurons and, notably, reduced or eliminated aging differences in the biomarkers. Thus, this study provides the first evidence that altered CICR plays a role in driving the early and simultaneous emergence in hippocampus of multiple Ca 2ϩ -related biomarkers of aging.

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“…In brain neurons from aging rodents and rabbits, as compared with neurons from younger animals, Ca 2+ influx associated with action potentials induces a larger Ca 2+ -dependent afterhyperpolarization (AHP) (Landfield and Pitler 1984;Moyer et al 1992;Potier et al 1992;Disterhoft et al 2004;Stutzmann et al 2006) and impairs shortterm synaptic plasticity (Landfield et al 1986;Thibault et al 2001). Furthermore, these findings have been reinforced by studies showing that pharmacologically isolated Ca 2+ action potentials (Pitler and Landfield 1990;Disterhoft et al 1996), whole-cell Ca 2+ currents (Campbell et al 1996), and Ca 2+ transients during repetitive spike trains also are larger in hippocampal neurons from aged animals (Thibault et al 2001;Hemond and Jaffe 2005). An apparent excess Ca 2+ influx via L-type voltage-gated Ca 2+ channels (L-VGCC) appears to be involved in this Ca 2+ dysregulation (Landfield 1996;Thibault et al 1998).…”

mentioning

confidence: 99%

Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes

Galeotti¹,

Quattrone²,

Vivoli³

et al. 2008

Learn. Mem.

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The administration of the ryanodine receptor (RyR) agonist 4-Cmc (0.003-9 nmol per mouse intracerebroventricularly [i.c.v.]) ameliorated memory functions, whereas the RyR antagonist ryanodine (0.0001-1 nmol per mouse i.c.v.) induced amnesia in the mouse passive avoidance test. The role of the type 1, 2, and 3 RyR isoforms in memory processes was then evaluated by inhibiting the expression of the three RyR proteins in the mouse brain. A selective knockdown of the RyR isoforms was obtained by the i.c.v. administration of antisense oligonucleotides (aODNs) complementary to the sequence of RyR1, RyR2 and RyR3 proteins, as demonstrated by immunoblotting experiments. RyR1 (5-9 nmol per mouse i.c.v.) knockdown mice did not show any memory dysfunction. Conversely, RyR2 (1-7 nmol per mouse i.c.v.) and RyR3 (1-7 nmol per mouse i.c.v.) knockdown animals showed an impairment of memory processes. This detrimental effect was temporary and reversible, disappearing 7 d after the end of the aODN treatment. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous mobility and inspection activity, as revealed by the hole-board test. In conclusion, the lack of any involvement of cerebral RyR1 was demonstrated. These findings also showed the involvement of type 2 and type 3 RyR in the modulation of memory functions identifying these cerebral RyR isoforms as critical targets underlying memory processes.

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Caloric restriction prevents aging-associated changes in spike-mediated Ca2+ accumulation and the slow afterhyperpolarization in hippocampal CA1 pyramidal neurons

Cited by 41 publications

References 56 publications

Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

Early and Simultaneous Emergence of Multiple Hippocampal Biomarkers of Aging Is Mediated by Ca²⁺-Induced Ca²⁺Release

Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes

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Caloric restriction prevents aging-associated changes in spike-mediated Ca2+ accumulation and the slow afterhyperpolarization in hippocampal CA1 pyramidal neurons

Cited by 41 publications

References 56 publications

Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

Early and Simultaneous Emergence of Multiple Hippocampal Biomarkers of Aging Is Mediated by Ca2+-Induced Ca2+Release

Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes

Contact Info

Product

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Early and Simultaneous Emergence of Multiple Hippocampal Biomarkers of Aging Is Mediated by Ca²⁺-Induced Ca²⁺Release