# Temporal Progression of Recognition Memory Impairment, Astrogliosis, and Cholinergic Dysfunction in the Streptozotocin Rat Model of Sporadic Alzheimer’s Disease

**Authors:** Sofía Niño-Rivero, Rossana Cabral, Jazmín Fleitas, Lucía Alcalde-Ahlig, Eduardo M. Castaño, Laura Morelli, Ronald McGregor, Pablo Galeano, Patricia Lagos

PMC · DOI: 10.3390/ijms262210944 · International Journal of Molecular Sciences · 2025-11-12

## TL;DR

This study tracks memory decline and brain changes in a rat model of Alzheimer's disease over time.

## Contribution

The study reveals the temporal sequence of astrogliosis and cholinergic dysfunction preceding memory impairment in Alzheimer's.

## Key findings

- Recognition memory impairment begins in the intermediate stage and continues into later stages.
- Astrogliosis is evident as early as 15 days post-STZ administration.
- Cholinergic changes start in the intermediate stage without neuronal loss.

## Abstract

The streptozotocin (STZ) experimental model of sporadic Alzheimer’s disease (SAD), the most prevalent form of this type of dementia, has become a valuable tool to study the behavioral and morphological changes that occur during the gradual development of this pathology. We used the STZ experimental model in combination with the novel object recognition test (NORT) and immunohistochemical techniques to evaluate the recognition memory decline and morphological alterations in memory-related structures (hippocampus and cortex). Our analysis included five different time points after intracerebroventricular (ICV) administration of 3 mg/kg of STZ or artificial cerebrospinal fluid (aCSF) as a control. The time points included three distinct stages: early (15 and 30 days), intermediate (60 days), and late (90 and 120 days). We found that recognition memory impairment started in the intermediate stage and persisted through the later stages. Morphologically, we detected significant astrogliosis starting in the early stages, whereas cholinergic changes began in the intermediate stage. No neuronal loss was observed at any of the time points analyzed. Our results further support the hypothesis that astrogliosis constitutes an initial pathological event that may compromise the hippocampal cholinergic system and can contribute to the onset of recognition memory deficits.

## Linked entities

- **Chemicals:** streptozotocin (PubChem CID 29327)
- **Diseases:** Alzheimer’s disease (MONDO:0004975)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Diseases:** Cholinergic Dysfunction (MESH:C535672), Memory Impairment (MESH:D008569), Alzheimer's Disease (MESH:D000544), neuronal loss (MESH:D009410), memory decline (MESH:D060825), Astrogliosis (MESH:D005911), dementia (MESH:D003704)
- **Chemicals:** STZ (MESH:D013311)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12652115/full.md

## References

81 references — full list in the complete paper: https://tomesphere.com/paper/PMC12652115/full.md

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Source: https://tomesphere.com/paper/PMC12652115