Evidence map›Paper›PMID 42726148›Full record

ArticleMetabolic brain disease2026

Neuroprotective impact of nicotinamide riboside and metformin on the hippocampus of male rats with diet-induced obesity.

Zahra Nasiri, Hora Amoozegar, Asma Sobhani, Mohammad Saeedi, Zahra Hosseinpour, Bahareh Hassanzadeh, Mohammadreza Aghabali, Mobin Alinia, Meysam Rahimipour, Mohammad Hojjati Far and 2 more

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Article in Metabolic brain disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Zahra NasiriDepartment of Medical Virology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.ORCID http://orcid.org/0009-0003-6523-422X
Hora AmoozegarSchool of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.ORCID http://orcid.org/0009-0009-8509-3747
Asma SobhaniDepartment of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Mohammad SaeediDepartment of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.ORCID http://orcid.org/0009-0006-0580-0906
Zahra HosseinpourDepartment of Psychology, Islamic Azad University, Amol Branch, Amol, Iran.
Bahareh HassanzadehAston Pharmacy School, College of Health & Life Sciences, Aston University, Birmingham, UK.
Mohammadreza AghabaliFaculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University (IAUPS), Tehran, Iran.ORCID http://orcid.org/0009-0006-0699-8280
Mobin AliniaDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.ORCID http://orcid.org/0009-0004-3137-810X
Meysam RahimipourCognitive Neuroscience, Department of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0009-0008-7244-7158
Mohammad Hojjati FarDepartment of Medical Physiology, Shiraz University of Medical Science, Shiraz, Iran. M.hojjatifar2024@gmail.com.ORCID http://orcid.org/0009-0009-7358-1815
Mehrangiz GhafariDepartment of Pathology, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran. ghafari@zbmu.ac.ir.ORCID http://orcid.org/0000-0003-2942-4651
Elham NadimiHistomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. immunolog8@sums.ac.ir.ORCID http://orcid.org/0000-0003-0153-2650

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundObesity-induced metabolic disturbances are increasingly recognized as major contributors to hippocampal dysfunction and neurodegeneration. Chronic exposure to a high-fat diet (HFD) has been associated with hippocampal structural alterations, dysregulation of neurotrophic and metabolic signalling, and increased neuronal vulnerability, ultimately impairing cognitive performance.

objectiveThis study investigated the neuroprotective effects of nicotinamide riboside (NR), metformin (MET), and their combination on hippocampal structure, gene expression, and spatial memory in a male rat model of diet-induced obesity.

methodsMale Wistar rats were assigned to a lean control group or a high-fat diet (HFD) group and maintained on their respective diets for 10 weeks. During the final 4 weeks of the HFD protocol, HFD-fed rats received nicotinamide riboside (NR; 300 mg/kg/day), metformin (MET; 200 mg/kg/day), or their combination by oral gavage while continuing HFD feeding. Stereological analysis was performed to assess hippocampal subregion volumes (CA1 and dentate gyrus), neuronal survival, and total glial cell counts based on morphological criteria. Gene expression levels of Bdnf, Sirt1, Ppargc1a, Bax, Bcl-2, and Casp3 were measured using quantitative real-time PCR (qRT-PCR). Spatial learning and memory were evaluated using the Morris Water Maze (MWM) test.

resultsHFD feeding induced obesity accompanied by hippocampal atrophy, altered expression of neurotrophic, metabolic, and apoptosis-related genes, and impaired spatial memory. Treatment with NR and MET, particularly in combination, was associated with attenuation of these alterations. The combination treatment showed the greatest improvement in hippocampal volume, greater neuronal preservation, reduced morphologically identified glial cell counts, and partial normalization of gene expression patterns. Behavioral analysis also indicated better performance in spatial learning and memory, with the NR + MET group showing the most pronounced improvement in escape latency and time spent in the target quadrant.

conclusionNR and metformin were associated with beneficial effects on obesity-related hippocampal alterations, accompanied by favourable changes in apoptosis-related, metabolic, and neurotrophic gene expression as well as improved stereological indices of hippocampal integrity. The combined treatment generally produced greater improvements than either monotherapy. These findings support further investigation of NR and metformin as potential interventions for obesity-associated hippocampal dysfunction and cognitive impairment.

Indexed as

Diet, High-FatHippocampusMetforminNeuroprotective AgentsNiacinamideObesityPyridinium CompoundsAnimalsMaleMaze LearningRatsRats, WistarSpatial MemoryMetforminNeuroprotective AgentsNiacinamidenicotinamide-beta-ribosidePyridinium CompoundsAMPKApoptosisBdnfHippocampal stereologyHippocampusMetforminMorris water mazeNicotinamide ribosideObesitySirt1

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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.