# Involvement of synaptophysin and microtubule-associated protein 2 in the neuroprotective effect of berberine in an amyloid β-induced rat model of Alzheimer's disease

**Authors:** Mohammad-Hadi Akbarizadeh-Mashkani, Siamak Afshinmajd, Saeid Iranzadeh, Mehrdad Roghani

PMC · DOI: 10.22038/ajp.2025.26026 · 2025-11-01

## TL;DR

Berberine protects against Alzheimer's-related cognitive decline in rats by reducing brain damage and improving synaptic health.

## Contribution

The study reveals berberine's neuroprotective role via synaptophysin and MAP2 in an amyloid β-induced Alzheimer's rat model.

## Key findings

- Berberine improved cognitive performance in Y-maze and novel object recognition tests.
- Berberine reduced oxidative stress and inflammation markers in the hippocampus.
- Berberine enhanced synaptic proteins synaptophysin and MAP2 and reduced neuronal loss.

## Abstract

Alzheimer’s disease (AD) is a major public health concern. Berberine has shown promise in animal models by improving memory retention through multiple mechanisms. This study aimed to evaluate berberine therapeutic potential in ameliorating cognitive deficits in a rat AD model induced by intrahippocampal amyloid β1-42.

The AD model was induced through bilateral injection of amyloid β1-42 into the CA1 region of the hippocampus. Berberine was administered orally, starting one hour post-surgery for one week. Rats were divided into sham, amyloid β, amyloid β + berberine 10 mg/kg, and amyloid β + berberine 50 mg/kg groups. The assessments encompassed cognitive testing and analysis of hippocampal markers, including oxidative stress, inflammation, apoptosis, and synaptic plasticity. Additionally, we evaluated acetylcholinesterase (AChE) activity and quantified neuronal loss in the hippocampal CA1 region.

Berberine improved the cognitive performance of amyloid-microinjected rats in the Y-maze, novel object recognition, and passive avoidance tests in a dose-dependent manner. Berberine attenuated hippocampal levels of malondialdehyde (MDA), nitrite, and tumor necrosis factor α (TNFα). Furthermore, berberine improved the activity of superoxide dismutase (SOD) and reduced caspase-3 and AChE activity. Berberine also enhanced synaptophysin and microtubule-associated protein 2 (MAP2) levels and inhibited neuronal loss in the CA1 region.

Berberine demonstrated protective effects against amyloid β-induced cognitive deficits in a rat AD model, and these effects were associated with reduced oxidative and nitrosative stress, inflammation, apoptosis, and AChE activity, alongside enhanced synaptic protection.

## Linked entities

- **Proteins:** Casp3 (caspase 3)
- **Chemicals:** berberine (PubChem CID 2353), malondialdehyde (PubChem CID 10964), nitrite (PubChem CID 946)
- **Diseases:** Alzheimer's disease (MONDO:0004975)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Syp (synaptophysin) [NCBI Gene 24804] {aka Syp1}, Map2 (microtubule-associated protein 2) [NCBI Gene 25595] {aka MAP2R, Mtap2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Ache (acetylcholinesterase) [NCBI Gene 83817]
- **Diseases:** AD (MESH:D000544), amyloid (MESH:C000718787), cognitive deficits (MESH:D003072), neuronal loss (MESH:D009410), inflammation (MESH:D007249)
- **Chemicals:** MDA (MESH:D008315), Berberine (MESH:D001599), nitrite (MESH:D009573), amyloid beta1-42 (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12777669/full.md

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Source: https://tomesphere.com/paper/PMC12777669