Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology

Eslamizade, Mohammad Javad; Saffarzadeh, Fatemeh; Mousavi, Sayed Mostafa Modarres; Meftahi, Gholam Hossein; Hosseinmardi, Narges; Mehdizadeh, Mehdi; Janahmadi, Mahyar

doi:10.1016/j.neuroscience.2015.07.087

Cited by 41 publications

(40 citation statements)

References 75 publications

(58 reference statements)

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“…The exact mechanism by which A β creates these adverse neuronal defects is not known with any certainty due to the plethora of cellular abnormalities that this protein promotes, such as forming cation-permeable pores in the plasma membrane [33–37], altering channel activity [12, 38, 39], and affecting synaptic signaling [20]. Using Hodgkin-Huxley formalism in conjunction with dynamic ion concentrations, we have reproduced many experimentally observed changes in the behavior of inhibitory neurons from APdE9 mice including the inability to reliably spike, higher resting membrane potential, enhanced depolarizability in response to applied stimulus, and smaller mean action potential amplitude as compared to those from NTG mice.…”

Section: Discussionmentioning

confidence: 99%

“…A recent experimental study reported significant decrease in the excitability of A β -treated pyramidal cells from CA1 region of Hippocampus that was attributed to upregulated I h current [38]. Saito et al on the other hand observed a significant reduction in HCN channel level in the temporal lobe of cynomolgus monkeys during aging and the temporal lobe of sporadic AD patients.…”

Section: Discussionmentioning

confidence: 99%

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Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer’s Disease

2016

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Alzheimer’s disease (AD) is characterized by the abnormal proteolytic processing of amyloid precursor protein, resulting in increased production of a self-aggregating form of beta amyloid (Aβ). Several lines of work on AD patients and transgenic mice with high Aβ levels exhibit altered rhythmicity, aberrant neuronal network activity and hyperexcitability reflected in clusters of hyperactive neurons, and spontaneous epileptic activity. Recent studies highlight that abnormal accumulation of Aβ changes intrinsic properties of inhibitory neurons, which is one of the main reasons underlying the impaired network activity. However, specific cellular mechanisms leading to interneuronal dysfunction are not completely understood. Using extended Hodgkin-Huxley (HH) formalism in conjunction with patch-clamp experiments, we investigate the mechanisms leading to the impaired activity of interneurons. Our detailed analysis indicates that increased Na+ leak explains several observations in inhibitory neurons, including their failure to reliably produce action potentials, smaller action potential amplitude, increased resting membrane potential, and higher membrane depolarization in response to a range of stimuli in a model of APPSWE/PSEN1DeltaE9 (APdE9) AD mice as compared to age-matched control mice. While increasing the conductance of hyperpolarization activated cyclic nucleotide-gated (HCN) ion channel could account for most of the observations, the extent of increase required to reproduce these observations render such changes unrealistic. Furthermore, increasing the conductance of HCN does not account for the observed changes in depolarizability of interneurons from APdE9 mice as compared to those from NTG mice. None of the other pathways tested could lead to all observations about interneuronal dysfunction. Thus we conclude that upregulated sodium leak is the most likely source of impaired interneuronal function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer’s Disease

2016

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“…29 In a recent study, Eslamizade et al, 2015 have suggested that Ab could influence excitability of these neurons through modification of the activity of TRPV1. 30 They conclude that dysregulation of PIP2 metabolism by Ab could be partly responsible for neuronal death through changes in TRPV1 function.…”

Section: Trpv Subfamilymentioning

confidence: 99%

“…TRPV4 is a channel activated by temperatures that range from [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] C, by changes in osmotic pressure and by molecules of a lipid nature which are downstream of the activity of PLC, 39 among others. In this case, binding of PIP2 to the N-terminus of TRPV4 was shown to be important for activation of the channel by heat and hypotonic stimuli.…”

mentioning

confidence: 99%

Regulation of thermoTRPs by lipids

2016

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The family of Transient Receptor Potential (TRP) ion channels is constituted by 7 subfamilies among which are those that respond to temperature, the thermoTRPs. These channels are versatile molecules of a polymodal nature that have been shown to be modulated in various fashions by molecules of a lipidic nature. Some of these molecules interact directly with the channels on specific regions of their structures and some of these promote changes in membrane fluidity or modify their gating properties in response to their agonists. Here, we have discussed how some of these lipids regulate the activity of thermoTRPs and included some of the available evidence for the molecular mechanisms underlying their effects on these channels.

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“…Therefore, NO is a neuronal messenger mediating the release of DA in the CA1 area of the rat hippocampus (Eslamizade et al, 2015; Ghodrat, Sahraei, Razjouyan, & Meftahi, 2014; Gholami et al, 2003; Karami, et al, 2003; Karami et al, 2002). It has been proposed that damage to the dorsal hippocampus interferes with spatial learning.…”

Section: Role Of Nitric Oxide On Morphine-induced Conditioned Placmentioning

confidence: 99%

Review Paper: Role of Nitric Oxide on Dopamine Release and Morphine-Dependency

Motahari

Sahraei

Meftahi

2016

BCN

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The catastrophic effects of opioids use on public health and the economy are documented clearly in numerous studies. Repeated morphine administration can lead to either a decrease (tolerance) or an increase (sensitization) in its behavioral and rewarding effects. Morphine-induced sensitization is a major problem and plays an important role in abuse of the opioid drugs. Studies reported that morphine may exert its effects by the release of nitric oxide (NO). NO is a potent neuromodulator, which is produced by nitric oxide synthase (NOS). However, the exact role of NO in the opioid-induced sensitization is unknown. In this study, we reviewed the role of NO on opioid-induced sensitization in 2 important, rewarding regions of the brain: nucleus accumbens and ventral tegmentum. In addition, we focused on the contribution of NO on opioid-induced sensitization in the limbic system.

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Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology

Cited by 41 publications

References 75 publications

Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer’s Disease

Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer’s Disease

Regulation of thermoTRPs by lipids

Review Paper: Role of Nitric Oxide on Dopamine Release and Morphine-Dependency

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