Early derailment of firing properties in CA1 pyramidal cells of the ventral hippocampus in an Alzheimer's disease mouse model

Spoleti, Elena; Krashia, Paraskevi; Barbera, Livia La; Nobili, Annalisa; Lupaşcu, Carmen Alina; Giacalone, E.; Keller, Flavio; Migliore, Michele; Renzi, Massimiliano; D’Amelio, Marcello

doi:10.1016/j.expneurol.2021.113969

Cited by 18 publications

(22 citation statements)

References 116 publications

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“…However, the future direction of KCNQ neural mechanosensation literature ought to focus more on the clinical and translational use of these pharmacotherapeutic options, as most of the literature used to support this review was based on animal models alone. Despite this, there is strong evidence that could support the initiation of future clinical trials, especially for auditory pathologies as well as in PD [ 14 , 80 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ], and developments for understanding the effects that antimicrobial agents have on these potassium ion channels [ 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. Additionally, the scope of this review was on neural modulation, yet there is a growing amount of literature on the behavior of KCNQ channels in cardiac modulations as well, especially in the cellular processes involved in arrhythmia [ 26 , 27 , 28 , 29 , 139 , 140 , 141 ,…”

Section: Discussionmentioning

confidence: 99%

“…This is where the literature ought to focus in order to determine if secondary factors that are not understood in these animal models also contribute to the memory impairment (i.e., hippocampal morphology) [ 90 , 91 , 92 , 93 , 94 , 95 ]. The epileptic phenotype, in conjunction with the cognitive impairment of these genetic models, may suggest additional psychomotor exploration [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ].…”

Section: Modulation Of Synaptic Plasticity By Kcnq Channelsmentioning

confidence: 99%

“…While this avenue of study has proven to be a promising utilization of these K + channels in dopaminergic pathways, they are perhaps better associated with the treatment of motor disorders involving the neurotransmitter dopamine. Parkinson’s disease (PD) is a neurodegenerative disorder commonly associated with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. As a result, the loss of nigrostriatal dopamine is associated with the motor symptoms classically observed in PD, such as muscular rigidity, bradykinesia, and tremor [ 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ].…”

Section: Kcnq Channels In Dopaminergic Motor Disordersmentioning

confidence: 99%

“…Activators of the KCNQ channels in the substantia nigra, such as retigabine (a KCNQ2-5 opener), can induce an inhibitory control of nigrostriatal neurons through increased K + conductance [ 96 , 97 ]. This effect is able to attenuate the activity of dopaminergic neurons, diminishing the amount of dopamine released in the SNc.…”

Section: Kcnq Channels In Dopaminergic Motor Disordersmentioning

confidence: 99%

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Behavior of KCNQ Channels in Neural Plasticity and Motor Disorders

et al. 2022

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The broad distribution of voltage-gated potassium channels (VGKCs) in the human body makes them a critical component for the study of physiological and pathological function. Within the KCNQ family of VGKCs, these aqueous conduits serve an array of critical roles in homeostasis, especially in neural tissue. Moreover, the greater emphasis on genomic identification in the past century has led to a growth in literature on the role of the ion channels in pathological disease as well. Despite this, there is a need to consolidate the updated findings regarding both the pharmacotherapeutic and pathological roles of KCNQ channels, especially regarding neural plasticity and motor disorders which have the largest body of literature on this channel. Specifically, KCNQ channels serve a remarkable role in modulating the synaptic efficiency required to create appropriate plasticity in the brain. This role can serve as a foundation for clinical approaches to chronic pain. Additionally, KCNQ channels in motor disorders have been utilized as a direction for contemporary pharmacotherapeutic developments due to the muscarinic properties of this channel. The aim of this study is to provide a contemporary review of the behavior of these channels in neural plasticity and motor disorders. Upon review, the behavior of these channels is largely dependent on the physiological role that KCNQ modulatory factors (i.e., pharmacotherapeutic options) serve in pathological diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Modulation Of Synaptic Plasticity By Kcnq Channelsmentioning

confidence: 99%

Section: Kcnq Channels In Dopaminergic Motor Disordersmentioning

confidence: 99%

Section: Kcnq Channels In Dopaminergic Motor Disordersmentioning

confidence: 99%

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Behavior of KCNQ Channels in Neural Plasticity and Motor Disorders

et al. 2022

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“…Alzheimer’s disease is a complicated and multifactorial disorder, and many hypotheses have been developed, including Aβ ( Selkoe and Hardy, 2016 ), tau ( Arnsten et al, 2021 ), cholinergic ( Terry and Buccafusco, 2003 ; Chen and Mobley, 2019 ), and dopaminergic degeneration ( Nobili et al, 2017 ; Cordella et al, 2018 ; De Marco and Venneri, 2018 ; Serra et al, 2018 , 2021 ; Bozzali et al, 2019 ; Iaccarino et al, 2020 ; Venneri and De Marco, 2020 ; La Barbera et al, 2021 ; Sala et al, 2021 ; Spoleti et al, 2022 ), oxidative stress ( Markesbery, 1997 ), inflammation ( Kinney et al, 2018 ), etc. How much further we have to go before deciphering all the molecular mechanisms underlying the onset and evolution of AD and, in turn, the putative druggable targets of the disease is not yet known, however, many studies have been done to find a potential therapeutic strategy.…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer’s disease: Current trends and future perspectives

et al. 2022

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Alzheimer’s disease (AD), the most common form of dementia, is a progressive and multifactorial neurodegenerative disorder whose primary causes are mostly unknown. Due to the increase in life expectancy of world population, including developing countries, AD, whose incidence rises dramatically with age, is at the forefront among neurodegenerative diseases. Moreover, a definitive cure is not yet within reach, imposing substantial medical and public health burdens at every latitude. Therefore, the effort to devise novel and effective therapeutic strategies is still of paramount importance. Genetic, functional, structural and biochemical studies all indicate that new and efficacious drug delivery strategies interfere at different levels with various cellular and molecular targets. Over the last few decades, therapeutic development of nanomedicine at preclinical stage has shown to progress at a fast pace, thus paving the way for its potential impact on human health in improving prevention, diagnosis, and treatment of age-related neurodegenerative disorders, including AD. Clinical translation of nano-based therapeutics, despite current limitations, may present important advantages and innovation to be exploited in the neuroscience field as well. In this state-of-the-art review article, we present the most promising applications of polymeric nanoparticle-mediated drug delivery for bypassing the blood-brain barrier of AD preclinical models and boost pharmacological safety and efficacy. In particular, novel strategic chemical functionalization of polymeric nanocarriers that could be successfully employed for treating AD are thoroughly described. Emphasis is also placed on nanotheranostics as both potential therapeutic and diagnostic tool for targeted treatments. Our review highlights the emerging role of nanomedicine in the management of AD, providing the readers with an overview of the nanostrategies currently available to develop future therapeutic applications against this chronic neurodegenerative disease.

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