Evidence map›Paper›PMID 36918475›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2023

Memantine/Aripiprazole Combination Alleviates Cognitive Dysfunction in Valproic Acid Rat Model of Autism: Hippocampal CREB/BDNF Signaling and Glutamate Homeostasis.

Sohir M Zohny, Mohamed Z Habib, Magda I Mohamad, Wael M Elayat, Reham M Elhossiny, Mohamed F Abd El-Salam, Ghada A M Hassan, Sawsan Aboul-Fotouh

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PubMed Full text at PMC Publisher
In one paragraph

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 2 pooled it
9.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Sohir M ZohnyDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
Mohamed Z HabibDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, 11566, Egypt. Mohamed.habib@med.asu.edu.eg.ORCID 0000-0001-7161-8121
Magda I MohamadDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Wael M ElayatDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Reham M ElhossinyDepartment of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Mohamed F Abd El-SalamPhysiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Ghada A M HassanNeuropsychiatry Department, Faculty of Medicine, Galala University, Al Galala, Egypt.
Sawsan Aboul-FotouhDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
Ain Shams University · EG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Significant efforts are increasingly directed towards identifying novel therapeutic targets for autism spectrum disorder (ASD) with a rising role of aberrant glutamatergic transmission in the pathogenesis of ASD-associated cellular and behavioral deficits. This study aimed at investigating the role of chronic memantine (20 mg/kg/day) and aripiprazole (3 mg/kg/day) combination therapy in the management of prenatal sodium valproate (VPA)-induced autistic-like/cognitive deficits in male Wistar rats. Pregnant female rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like behaviors in their offspring. Prenatal VPA induced autistic-like symptoms (decreased social interaction and the appearance of stereotyped behavior) with deficits in spatial learning (in Morris water maze) and cognitive flexibility (in the attentional set-shifting task) in addition to decreased hippocampal protein levels of phosphorylated cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and gene expression of glutamate transporter-1 (Glt-1) with a decline in GABA/glutamate ratio (both measured by HPLC). These were accompanied by the appearance of numerous neurofibrillary tangles (NFTs) with enhanced apoptosis in hippocampal sections. Memantine/aripiprazole combination increased the protein levels of p-CREB, BDNF, and Glt-1 gene expression with restoration of GABA/glutamate balance, attenuation of VPA-induced neurodegenerative changes and autistic-like symptoms, and improvement of cognitive performance. This study draws attention to the favorable cognitive effects of memantine/aripiprazole combination in autistic subjects which could be mediated via enhancing CREB/BDNF signaling with increased expression of astrocytic Glt-1 and restoration of GABA/glutamate balance, leading to inhibition of hippocampal NFTs formation and neuronal apoptosis.

Indexed as

Autism Spectrum DisorderAutistic DisorderCognitive DysfunctionAnimalsAripiprazoleBrain-Derived Neurotrophic FactorCyclic AMP Response Element-Binding ProteinDisease Models, AnimalFemalegamma-Aminobutyric AcidGlutamatesHippocampusHomeostasisMaleMemantinePregnancyAripiprazoleBrain-Derived Neurotrophic FactorCreb1 protein, ratCyclic AMP Response Element-Binding Proteingamma-Aminobutyric AcidGlutamatesMemantineValproic AcidAripiprazoleAstrocyteAutism spectrum disorderCognitive dysfunctionGlutamateMemantine

Identifiers

PMID36918475
PMCPMC10121975
OpenAlexW4324134270

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.