Efficacy of Memantine as Adjunct Therapy for Autism Spectrum Disorder in Children Aged &lt;14 Years

Karahmadi, Mojgan; Tarrahi, Mohammad Javad; Ardestani, Samaneh Sadat Vatankhah; Omranifard, Victoria; Farzaneh, Behdad

doi:10.4103/abr.abr_100_18

Cited by 20 publications

(6 citation statements)

References 27 publications

(29 reference statements)

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“…The NMDAR antagonist MEM has already been used in adjunct therapy for autism. 63 , 64 Our results suggest that other proteins in the glutamatergic system, such as glutamine synthetase and transporters, could be potential therapeutic targets for autism.…”

Section: Discussionmentioning

confidence: 75%

Increased NMDARs in neurons and glutamine synthetase in astrocytes underlying autistic-like behaviors of Gabrb1−/− mice

Wang¹,

Gao²,

Xiao³

et al. 2023

iScience

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Section: Discussionmentioning

confidence: 75%

Increased NMDARs in neurons and glutamine synthetase in astrocytes underlying autistic-like behaviors of Gabrb1−/− mice

Wang¹,

Gao²,

Xiao³

et al. 2023

iScience

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“…These results also suggest that the NMDAR system can be targeted in designing therapy for autism. Since the NMDAR antagonist memantine is used in adjunct therapy for autism 65 , 66 , other proteins in the NMDAR pathways can be potential therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Upregulated NMDAR-enhanced GABAergic transmission underlies autistic-like deficits in Htr3a knockout mice

et al. 2021

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Mutations in serotonin pathway genes, especially the serotonergic receptor subunit gene HTR3A , are associated with autism. However, the association of HTR3A deficiency with autism and the underlying mechanisms remain unknown. Methods: The Htr3a knockout (KO) mice were generated using transcription activator-like effector nuclease technology. Various behavior tests, including social interaction, social approach task, olfactory habituation/dishabituation, self-grooming, novel object recognition, contextual fear conditioning, elevated plus maze, open field and seizure susceptibility, were performed to assess the phenotypes. Transcriptome sequencing was carried out to search for molecular network and pathways underlying the phenotypes. Electrophysiological recordings, immunoblotting, immunofluorescence staining, immunoprecipitation, and quantitative real-time PCR were performed to verify the potential mechanisms. The N-methyl-D-aspartate receptor (NMDAR) antagonist memantine was used to treat the KO mice for rescuing the phenotypes. Results: The Htr3a KO mouse model showed three phenotypic domains: autistic-like behaviors (including impaired social behavior, cognitive deficits, and increased repetitive self-grooming), impaired memory, and attenuated susceptibility to pentylenetetrazol-induced seizures. We observed enhanced action potential-driven γ-aminobutyric acid-ergic (GABAergic) transmission in pyramidal neurons and decreased excitatory/inhibitory (E/I) ratio using the patch-clamp recording. Transcriptome sequencing on the hippocampus revealed the converged pathways of the dysregulated molecular networks underlying three phenotypic domains with upregulation of NMDAR. We speculated that Htr3a KO promotes an increase in GABA release through NMDAR upregulation. The electrophysiological recordings on hippocampal parvalbumin-positive (PV + ) interneuron revealed increased NMDAR current and NMDAR-dependent excitability. The NMDAR antagonist memantine could rescue GABAergic transmission in the hippocampus and ameliorate autistic-like behaviors of the KO mice. Conclusion: Our data indicated that upregulation of the NMDAR in PV + interneurons may play a critical role in regulating GABAergic input to pyramidal neurons and maybe involve in the pathogenesis of autism associated with HTR3A deficiency. Therefore, we suggest that the NMDAR system could be considered potential therapeutic target for autism.

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“…It works by blocking the excessive activation of NMDA receptors, which may help to restore the balance between excitation and inhibition in the brain. Several clinical trials have investigated the effectiveness of memantine in treating ASD, and the results have been mixed [ 32 - 34 ]. Other NMDA receptor modulators are also being studied as potential treatments for ASD.…”

Section: Improvement Of Excitation and Inhibition Imbalancesmentioning

confidence: 99%

Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies

Yenkoyan,

Ounanian,

Mirumyan

et al. 2024

CMC

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Autism spectrum disorder (ASD) is an umbrella term for developmental disorders characterized by social and communication impairments, language difficulties, restricted interests, and repetitive behaviors. Current management approaches for ASD aim to resolve its clinical manifestations based on the type and severity of the disability. Although some medications like risperidone show potential in regulating ASD-associated symptoms, a comprehensive treatment strategy for ASD is yet to be discovered. To date, identifying appropriate therapeutic targets and treatment strategies remains challenging due to the complex pathogenesis associated with ASD. Therefore, a comprehensive approach must be tailored to target the numerous pathogenetic pathways of ASD. From currently viable and basic treatment strategies, this review explores the entire field of advancements in ASD management up to cutting-edge modern scientific research. A novel systematic and personalized treatment approach is suggested, combining the available medications and targeting each symptom accordingly. Herein, summarize and categorize the most appropriate ways of modern ASD management into three distinct categories: current, promising, and prospective strategies.

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Efficacy of Memantine as Adjunct Therapy for Autism Spectrum Disorder in Children Aged <14 Years

Cited by 20 publications

References 27 publications

Increased NMDARs in neurons and glutamine synthetase in astrocytes underlying autistic-like behaviors of Gabrb1−/− mice

Increased NMDARs in neurons and glutamine synthetase in astrocytes underlying autistic-like behaviors of Gabrb1−/− mice

Upregulated NMDAR-enhanced GABAergic transmission underlies autistic-like deficits in Htr3a knockout mice

Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies

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