Age-related Changes in [3H]Nimodipine and [3H]Rolipram Binding in the Rat Brain

Araki, Tsutomu; Kato, Harubumi; Shuto, Katsuro; Itoyama, Yasuto

doi:10.1111/j.2042-7158.1997.tb06802.x

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…Aging is associated with specific impairments of hippocampal function, which is reflected in learning and memory deficit [31,48]. These deficits could be associated with the loss of synaptic contacts [49], silencing of synapses [32,50] or decrease of postsynaptic responsiveness [51] (for review see [52]). This is reflected in deficits in the generation of long term plasticity [31,52,53] as well as alterations in the generation of certain spontaneous oscillatory activities [33].…”

Section: Discussionmentioning

confidence: 99%

Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Balleza-Tapia¹,

Huanosta-Gutierrez²,

Marquez-Ramos³

et al. 2010

CAR

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Soluble amyloid beta (Abeta) oligomers might trigger early cognitive impairment in Alzheimer's Disease (AD) through the impairment of proper neuronal network function. We have recently shown that the short sequence Abeta(25-35) affects the spontaneous activity in hippocampal slices, when was added to the bath, at high nanomolar concentrations. In the present study, we aimed to characterize the effects of the oligomerized full length sequence Abeta(1-42) on the spontaneous network activity in the CA1 hippocampal area testing whether such effects are age dependent. By performing extracellular field recordings of spontaneous network activity of hippocampal slices, we found that an oligomerized solution of Abeta(1-42) (osAbeta) potently inhibit, in a dose-dependent manner, the spontaneous hippocampal network activity with an IC(50) of 0.4 +/- 3.2 nM and a maximal effect reached around 10 nM. While spontaneous hippocampal network activity is unaffected by age, the sensitivity of spontaneous hippocampal network activity to osAbeta (10 nM) appears to be increased in slices from older animals. Moreover, to see a significant reduction in spontaneous network activity in slices from animals in their second week of life 100nM osAbeta was needed. The osAbeta-induced reduction in hippocampal network activity is accompanied by a presynaptic reduction in both spontaneous and miniature synaptic potentials. Finally, we demonstrated that the effect produced by osAbeta on spontaneous network activity was specific, reversible and unrelated with cell death. In conclusion, our data show that osAbeta alters hippocampal network activity at concentrations commonly observed in AD patients and that such effect of osAbeta increase with age.

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Section: Discussionmentioning

confidence: 99%

Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Balleza-Tapia¹,

Huanosta-Gutierrez²,

Marquez-Ramos³

et al. 2010

CAR

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“…For instance, we found that the network activity generated by the OB can be reduced by the application of 30 nM Aβ in slices taken from 3-week-old animals (Figure 3), whereas it was necessary to apply 100 nM Aβ to induce a similar reduction in network activity of hippocampal slices taken from 2-week-old animals [52]. Aging has been associated with loss of synaptic contacts [83,84], silencing of synapses [83-85], or a decrease of postsynaptic responsiveness [83,84,86,87] and synaptic dynamics [68, for review see 87], which is reflected in deficits in the generation of certain spontaneous oscillatory activities [52,88]. It remains to be determined which of these phenomena is responsible for the age dependency of Aβ-induced OB network dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Amyloid Beta Inhibits Olfactory Bulb Activity and the Ability to Smell

2013

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Early olfactory dysfunction has been consistently reported in both Alzheimer’s disease (AD) and in transgenic mice that reproduce some features of this disease. In AD transgenic mice, alteration in olfaction has been associated with increased levels of soluble amyloid beta protein (Aβ) as well as with alterations in the oscillatory network activity recorded in the olfactory bulb (OB) and in the piriform cortex. However, since AD is a multifactorial disease and transgenic mice suffer a variety of adaptive changes, it is still unknown if soluble Aβ, by itself, is responsible for OB dysfunction both at electrophysiological and behavioral levels. Thus, here we tested whether or not Aβ directly affects OB network activity in vitro in slices obtained from mice and rats and if it affects olfactory ability in these rodents. Our results show that Aβ decreases, in a concentration- and time-dependent manner, the network activity of OB slices at clinically relevant concentrations (low nM) and in a reversible manner. Moreover, we found that intrabulbar injection of Aβ decreases the olfactory ability of rodents two weeks after application, an effect that is not related to alterations in motor performance or motivation to seek food and that correlates with the presence of Aβ deposits. Our results indicate that Aβ disrupts, at clinically relevant concentrations, the network activity of the OB in vitro and can trigger a disruption in olfaction. These findings open the possibility of exploring the cellular mechanisms involved in early pathological AD as an approach to reduce or halt its progress.

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“…7, No. 4,2001 central noradrenergic transmission. The hypothesis is that the increase of norepinephrine turnover, induced by rolipram in conjunction with the inhibitory action on cAMP metabolism, induces adaptive changes in central synapses more efficiently, resulting in a rapid onset of antidepressant activity.…”

Section: Antidepressant Effects Of Roliprammentioning

confidence: 99%

“…This effect is due to inhibition of PDE IV-mediated Ca 2+ -dependent cAMP hydrolysis (64). Rolipram also enhanced the excitability of neurons, providing a functional basis for cognition enhancement (4). Unlike conventional antidepressants, rolipram stimulates both the presynaptic and the postsynaptic components of monoaminergic transmission (11).…”

Section: Antidepressant Effects Of Roliprammentioning

confidence: 99%

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The Antidepressant and Antiinflammatory Effects of Rolipram in the Central Nervous System

2001

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Rolipram is a selective inhibitor of phosphodiesterases (PDE) IV, especially of the subtype PDE IVB. These phosphodiesterases are responsible for hydrolysis of the cyclic nucleotides cAMP and cGMP, particularly in nerve and immune cells. Consequences of rolipram-induced elevation of intracellular cAMP are increased synthesis and release of norepinephrine, which enhance central noradrenergic transmission, and suppress expression of proinflammatory cytokines and other mediators of inflammation. In humans and animals rolipram produces thereby a variety of biological effects. These effects include attenuation of endogenous depression and inflammation in the central nervous system (CNS), both effects are of potential clinical relevance. There are some discrepancies between in vitro and in vivo effects of rolipram, as well as between results obtained in animal models and clinical studies. The clinical use of rolipram is limited because of its behavioral and other side effects. Newly developed selective PDE IV inhibitors with presumably higher potency and lower toxicity are currently under investigation.

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Age-related Changes in [3H]Nimodipine and [3H]Rolipram Binding in the Rat Brain

Cited by 13 publications

References 31 publications

Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Amyloid Beta Inhibits Olfactory Bulb Activity and the Ability to Smell

The Antidepressant and Antiinflammatory Effects of Rolipram in the Central Nervous System

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Age-related Changes in [3H]Nimodipine and [3H]Rolipram Binding in the Rat Brain

Cited by 13 publications

References 31 publications

Amyloid &#946; Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Amyloid &#946; Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Amyloid Beta Inhibits Olfactory Bulb Activity and the Ability to Smell

The Antidepressant and Antiinflammatory Effects of Rolipram in the Central Nervous System

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Product

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Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner