Effect of Age on K<sup>+</sup>‐Induced Cytosolic Ca<sup>2+</sup> Changes in Rat Cortical Synaptosomes

Giovannelli, Lisa; Pepeu, Giancarlo

doi:10.1111/j.1471-4159.1989.tb07347.x

Cited by 39 publications

(16 citation statements)

References 34 publications

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“…Although it has been consistently demonstrated that calcium homeostasis is perturbed in the neurons of aged animals, the degree and/or direction of change depends on the structure examined and the method of evaluation used. For example, elevated resting levels of neuronal calcium, increased density of L-type calcium channels, and prolonged decay of calcium signals have been reported (Martinez et al 1988;Giovannelli and Pepeu 1989;Verkhratsky et al 1994;Villalba et al 1995;Thibault and Landfield 1996;Toescu and Verkhratsky 2000). These alterations in neuronal calcium homeostasis may yield a shift in the phosphatase-kinase ratio required for proper working memory function (Fig.…”

Section: Potential Substrates Contributing To Working Memorymentioning

confidence: 99%

Molecular activity underlying working memory

Dash¹,

et al. 2007

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The prefrontal cortex is necessary for directing thought and planning action. Working memory, the active, transient maintenance of information in mind for subsequent monitoring and manipulation, lies at the core of many simple, as well as high-level, cognitive functions. Working memory has been shown to be compromised in a number of neurological and psychiatric conditions and may contribute to the behavioral and cognitive deficits associated with these disorders. It has been theorized that working memory depends upon reverberating circuits within the prefrontal cortex and other cortical areas. However, recent work indicates that intracellular signals and protein dephosphorylation are critical for working memory. The present article will review recent research into the involvement of the modulatory neurotransmitters and their receptors in working memory. The intracellular signaling pathways activated by these receptors and evidence that indicates a role for G q -initiated PI-PLC and calcium-dependent protein phosphatase calcineurin activity in working memory will be discussed. Additionally, the negative influence of calcium-and cAMP-dependent protein kinase (i.e., calcium/calmodulin-dependent protein kinase II (CaMKII), calcium/diacylglycerol-activated protein kinase C (PKC), and cAMP-dependent protein kinase A (PKA)) activities on working memory will be reviewed. The implications of these experimental findings on the observed inverted-U relationship between D 1 receptor stimulation and working memory, as well as age-associated working memory dysfunction, will be presented. Finally, we will discuss considerations for the development of clinical treatments for working memory disorders.Working memory is the capacity to temporarily keep in mind information that is not currently present to the senses in order to monitor and manipulate this information for a particular purpose. Therefore, it is the ability to keep one's thought on information acquired in the past, in light of present demands, in order to plan one's actions to reach a future goal. An example of working memory is watching for traffic as one attempts to cross the street. As one turns to cross the street, one must keep in mind the position of the oncoming traffic, while monitoring and using this information to calculate the appropriate time to initiate the attempt. The relative position of the cars is the information that is being held for the period of seconds it takes to make the decision to walk or not. Crossing the street is the goal, or purpose, that requires one's thoughts to be direct and maintained on the traffic flow. Once the information is used, it is forgotten to minimize conflicts with subsequent decisions (Dudchenko 2004). The ability to integrate different information for planning and for goal-directed, purposeful action such as decision-making and problem-solving also requires working memory. For example, when a person is presented with a problem, a series of comparative evaluations must be done in order to determine the pros and cons for ...

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Section: Potential Substrates Contributing To Working Memorymentioning

confidence: 99%

Molecular activity underlying working memory

Dash¹,

et al. 2007

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“…However, there has been some controversy on this subject. Some studies, which were based on 45Ca measurements, reported decreased calcium uptake with aging (Peterson and Gibson, 1983;Leslie et al, 1985;Vitorica and Satrustegui, 1986;Giovannelli and Pepeu, 1989). In those studies, net calcium uptake was observed, where ionic calcium concentration and deposited calcium in organelles were not separately determined.…”

Section: Reduced Calcium Influx Into Aged Synapses Evoked By Depolarimentioning

confidence: 99%

“…As the voltage-dependent calcium influx is thought to be a prerequisite for activating the series of reactions leading to exocytosis and ACh release, calcium influx should be examined as the first step. Many studies using radiolabeled calcium have indicated decreased calcium influx into synaptosomes from aged rodents (Peterson and Gibson, 1983;Leslie et al, 1985;Victorica and Satrustegui, 1986;Giovannelli and Pepeu, 1989). It was not clear from these studies, however, whether the calcium uptake by the intrasynaptosomal mitochondria was taken into consideration.…”

Section: Introductionmentioning

confidence: 99%

Impaired synaptic functions with aging as characterized by decreased calcium influx and acetylcholine release

Tanaka

Hasegawa

Ando

1996

J of Neuroscience Research

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Age-related alterations of presynaptic functions were studied in terms of acetylcholine (ACh) synthesis and release using synaptosomes isolated from mouse brain cortices. The following three findings were obtained: 1) Choline acetyltransferase activity and ACh production rate remained constant throughout all ages tested. This observation, obtained with synaptosomes, was not consistent with data reported for brain slices (Gibson GE, Peterson C: J Neurochem 37:978-984, 1981). Various conditions, such as low glucose or membrane depolarization, modulated ACh synthesis to similar extents in young and aged synaptosomes. 2) Depolarization-induced release of ACh from synaptosomes significantly decreased in the senescent stage. The fraction of ACh released from aged synaptosomes was less than that released from young synaptosomes, although the ACh contents in the synaptosomes did not change with age. 3) Calcium influx induced by depolarization was lower in the synaptosomal preparations from aged mice than in those from young mice. A strong positive correlation was observed between the amounts of ACh released and the increased calcium levels when the data for all preparations, both from young and aged mice, were plotted. This indicates that diminished calcium influx may cause the reduced ACh release by aged synapses. The present study provides evidence for an age-related decrease in presynaptic functions, that is, a reduction in calcium influx via voltage-dependent calcium channels followed by a decreased ACh release from synapses despite an abundance of ACh within the synapses.

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“…1998). Synaptosomes from brains of aged rats demonstrated elevated resting levels and a slower decay in depolarization‐induced Ca 2+ transients than similar preparations from younger animals (Giovannelli and Pepeu 1989; Satrustegui et al. 1991; Michaelis et al.…”

mentioning

confidence: 99%

“…We have previously shown that both the activity and protein levels of PMCA are progressively reduced in synaptic plasma membranes (SPMs) with increasing age in both F344 and F344/BNF1 rats (Michaelis et al 1984(Michaelis et al , 1996Zaidi et al 1998). Synaptosomes from brains of aged rats demonstrated elevated resting levels and a slower decay in depolarization-induced Ca 2+ transients than similar preparations from younger animals (Giovannelli and Pepeu 1989;Satrustegui et al 1991;Michaelis et al 1992). The activity of PMCA is regulated by the Ca 2+ -binding protein CaM, and the amount of CaM tightly associated with SPMs is also markedly reduced in membranes from aged rat brain (Zaidi et al 1998).…”

mentioning

confidence: 99%

RNA_i– induced silencing of the plasma membrane Ca²⁺– ATPase 2 in neuronal cells: effects on Ca²⁺ homeostasis and cell viability

Fernandes¹,

Zaidi

Bean

et al. 2007

Journal of Neurochemistry

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Intraneuronal calcium ([Ca 2+ ] i ) regulation is altered in aging brain, possibly because of the changes in critical Ca 2+ transporters. We previously reported that the levels of the plasma membrane Ca 2+-ATPase (PMCA) and the V max for enzyme activity are significantly reduced in synaptic membranes in aging rat brain. The goal of these studies was to use RNA i techniques to suppress expression of a major neuronal isoform, PMCA2, in neurons in culture to determine the potential functional consequences of a decrease in PMCA activity. Embryonic rat brain neurons and SH-SY5Y neuroblastoma cells were transfected with in vitro -transcribed short interfering RNA or a short hairpin RNA expressing vector, respectively, leading to 80% suppression of PMCA2 expression within 48 h.

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Effect of Age on K⁺‐Induced Cytosolic Ca²⁺ Changes in Rat Cortical Synaptosomes

Cited by 39 publications

References 34 publications

Molecular activity underlying working memory

Molecular activity underlying working memory

Impaired synaptic functions with aging as characterized by decreased calcium influx and acetylcholine release

RNA_i– induced silencing of the plasma membrane Ca²⁺– ATPase 2 in neuronal cells: effects on Ca²⁺ homeostasis and cell viability

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Effect of Age on K+‐Induced Cytosolic Ca2+ Changes in Rat Cortical Synaptosomes

Cited by 39 publications

References 34 publications

Molecular activity underlying working memory

Molecular activity underlying working memory

Impaired synaptic functions with aging as characterized by decreased calcium influx and acetylcholine release

RNAi– induced silencing of the plasma membrane Ca2+– ATPase 2 in neuronal cells: effects on Ca2+ homeostasis and cell viability

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Product

Resources

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Effect of Age on K⁺‐Induced Cytosolic Ca²⁺ Changes in Rat Cortical Synaptosomes

RNA_i– induced silencing of the plasma membrane Ca²⁺– ATPase 2 in neuronal cells: effects on Ca²⁺ homeostasis and cell viability