Lamotrigine rescues neuronal alterations and prevents seizure-induced memory decline in an Alzheimer's disease mouse model

Rizzello, Emanuela; Pimpinella, Domenico; Pignataro, Annabella; Titta, Giulia; Merenda, Elisabetta; Saviana, Michela; Porcheddu, Gianfranco; Paolantoni, Chiara; Malerba, Francesca; Giorgi, Corinna; Curia, Giulia; Marchetti, Cristina

doi:10.1016/j.nbd.2023.106106

Cited by 12 publications

(4 citation statements)

References 81 publications

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“…They suggested that HCN1 subunits are positioned to provide a signature of flexibility in postsynaptic compartments in ERC layer II stellate cells, which becomes a signature of vulnerability when abrogated by advancing age. The latest evidence from animal studies indicates that LTG restores electrophysiological alterations, prevents memory deficits, and counteracts the increase in extracellular Aβ induced by seizures in pre-symptomatic Tg2576 mice -a transgenic model of AD [ 216 ]. Similarly, Fu et al (2023) [ 202 ] have shown that LTG substantially improved spatial cognitive deficits of APP/PS1 mice; alleviated damage to synapses and nerve cells in the brain; and reduced amyloid-β levels, tau protein hyperphosphorylation, and inflammatory responses.…”

Section: Hcn Dysregulation and Disruption In Age-related Memory Decli...mentioning

confidence: 99%

Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations

2024

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Increasing evidence indicates a role of hyperpolarization activated cation (HCN) channels in controlling the resting membrane potential, pacemaker activity, memory formation, sleep, and arousal. Their disfunction may be associated with the development of epilepsy and age-related memory decline. Neuronal hyperexcitability involved in epileptogenesis and EEG desynchronization occur in the course of dementia in human Alzheimer’s Disease (AD) and animal models, nevertheless the underlying ionic and cellular mechanisms of these effects are not well understood. Some suggest that theta rhythms involved in memory formation could be used as a marker of memory disturbances in the course of neurogenerative diseases, including AD. This review focusses on the interplay between hyperpolarization HCN channels, theta oscillations, memory formation and their role(s) in dementias, including AD. While individually, each of these factors have been linked to each other with strong supportive evidence, we hope here to expand this linkage to a more inclusive picture. Thus, HCN channels could provide a molecular target for developing new therapeutic agents for preventing and/or treating dementia.

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Section: Hcn Dysregulation and Disruption In Age-related Memory Decli...mentioning

confidence: 99%

Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations

2024

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“…(4) Dementia or AD is the result of a clinical diagnosis. (5) The article is available in English in its entirety. Gray literature and studies with full text unavailable were removed.…”

Section: Selection Criteriamentioning

confidence: 99%

“…Several mood stabilizers, such as lithium, valproate, and lamotrigine, are being tested for dementia or AD. However, lamotrigine, an antiepileptic medication, is primarily used to prevent epilepsy-induced memory loss [5], lessen anxiety and irritability [6], and prevent AD patients from having seizures that accelerate the disease [5]; valproate, on the other hand, can be used as an adjuvant to treat behavioral and psychological symptoms in both AD patients [7] and dementia patients [8], though its effectiveness is not statistically significant [9]. Furthermore, a firm agreement has not yet been established about the use of lamotrigine or valproate to treat AD and dementia in contemporary clinical practice, and there are also comparatively few studies on the subject.…”

Section: Introductionmentioning

confidence: 99%

Lithium Therapy’s Potential to Lower Dementia Risk and the Prevalence of Alzheimer’s Disease: A Meta-Analysis

Lu,

Lv,

Liu

et al. 2024

Eur Neurol

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Introduction: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore we conducted a meta-analysis. Methods: A systematic literature review was conducted in PubMed, Embase, and Web of Science. Comparison of the effects of lithium on Alzheimer's disease or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or Alzheimer's disease. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random effects model. Results: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of Alzheimer's disease (RR 0.59, 95% CI: 0.44-0.78), and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect the dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It's also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. Conclusion: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.

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“…Such effects of LTG were linked to its ability to suppress abnormal cortical hyperexcitability, enhance levels of neurotrophic factors, and decrease Aβ generation and deposition in this mouse model [ 55 ]. In addition, a very recent study on Tg 2576 mice also showed that LTG (10 mg/kg) could reduce seizure-induced cognitive deficits in the early stages of AD [ 56 ]. A study performed in APP/PS1 mice reported that LTG improved cognitive-like deficits by reducing synapse and neuronal damage in the CNS.…”

Section: Antiseizure Medications In Alzheimer’s Disease: Evidence Fro...mentioning

confidence: 99%

Antiseizure Medications in Alzheimer’s Disease from Preclinical to Clinical Evidence

Bosco

Guarnieri

Rania

et al. 2023

IJMS

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Alzheimer’s disease (AD) and epilepsy are common neurological disorders in the elderly. A bi-directional link between these neurological diseases has been reported, with patients with either condition carrying almost a two-fold risk of contracting the other compared to healthy subjects. AD/epilepsy adversely affects patients’ quality of life and represents a severe public health problem. Thus, identifying the relationship between epilepsy and AD represents an ongoing challenge and continuing need. Seizures in AD patients are often unrecognized because they are often nonconvulsive and sometimes mimic some behavioral symptoms of AD. Regarding this, it has been hypothesized that epileptogenesis and neurodegeneration share common underlying mechanisms. Targeted treatment to decrease epileptiform activity could represent a valuable strategy for delaying the neurodegenerative process and related cognitive impairment. Several preclinical studies have shown that some antiseizure medications (ASMs) targeting abnormal network hyperexcitability may change the natural progression of AD. However, to date, no guidelines are available for managing seizures in AD patients because of the paucity of randomized clinical trials sufficient for answering the correlated questions. Future AD clinical studies are mandatory to update clinicians about the symptomatic treatment of seizures in AD patients and recognize whether ASM therapy could change the natural progression of the disease, thereby rescuing cognitive performance.

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Lamotrigine rescues neuronal alterations and prevents seizure-induced memory decline in an Alzheimer's disease mouse model

Cited by 12 publications

References 81 publications

Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations

Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations

Lithium Therapy’s Potential to Lower Dementia Risk and the Prevalence of Alzheimer’s Disease: A Meta-Analysis

Antiseizure Medications in Alzheimer’s Disease from Preclinical to Clinical Evidence

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