Brain AT₁ Receptor Involvement in Cognitive Decline and Neuroinflammation in Streptozotocin-Treated Rats
- 1Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000, Argentina
- 2Laboratorio de Neurofarmacología, Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT-CONICET), Córdoba X5000, Argentina
Abstract
Neuroinflammation and oxidative stress are involved in neuropathologies related to learning and memory decline. Angiotensin II contributes to neuroinflammation through angiotensin II type 1 receptors (AT1-R), leading to oxidative stress and release of pro-inflammatory mediators. This study aimed to evaluate the role of brain angiotensin II, via AT1-R, in streptozotocin-induced cognitive decline and neuroinflammation. For this purpose, male Wistar rats were treated with the AT1-R blocker candesartan cilexetil (3 mg/kg) for 25 days. On days 12 and 14, the animals received an intraventricular injection of streptozotocin (3 mg/kg) each day. On day 25, they were tested for spatial, working, and declarative memory through the Morris water maze, holeboard, and novel object recognition tests, respectively. The oxidative stress marker, malondialdehyde, was measured in isolated brain microvessels. Cerebrospinal fluid was collected for tumor necrosis factor-α determination. The volume of the lateral ventricles was evaluated for morphological changes. The AT1-R blocker pretreatment prevented streptozotocin-induced declines in declarative and working memory. No changes in spatial and long-term memory were observed. Streptozotocin increased malondialdehyde in isolated microvessels and tumor necrosis factor-α levels, which were prevented by candesartan administration. All these findings are consistent with the involvement of AT1-R in early streptozotocin-induced changes, with behavioral and inflammatory/morphological outcomes likely mediated by overlapping yet partially distinct mechanisms.
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BibTeX
@article{perez2026brain,
title = {{Brain AT₁ Receptor Involvement in Cognitive Decline and Neuroinflammation in Streptozotocin-Treated Rats}},
author = {Mariela Fernanda Pérez and María de los Ángeles Marinzalda and Victoria Belén Occhieppo and Claudia Bregonzio and Gustavo Baiardi},
journal = {Current Issues in Molecular Biology},
year = {2026},
month = sep,
doi = {10.3390/cimb48100998},
url = {https://doi.org/10.3390/cimb48100998},
note = {CC BY},
}
RIS
TY - JOUR
TI - Brain AT₁ Receptor Involvement in Cognitive Decline and Neuroinflammation in Streptozotocin-Treated Rats
AU - Mariela Fernanda Pérez
AU - María de los Ángeles Marinzalda
AU - Victoria Belén Occhieppo
AU - Claudia Bregonzio
AU - Gustavo Baiardi
PY - 2026
DA - 2026/09/01
JO - Current Issues in Molecular Biology
DO - 10.3390/cimb48100998
UR - https://doi.org/10.3390/cimb48100998
AB - Neuroinflammation and oxidative stress are involved in neuropathologies related to learning and memory decline. Angiotensin II contributes to neuroinflammation through angiotensin II type 1 receptors (AT1-R), leading to oxidative stress and release of pro-inflammatory mediators. This study aimed to evaluate the role of brain angiotensin II, via AT1-R, in streptozotocin-induced cognitive decline and neuroinflammation. For this purpose, male Wistar rats were treated with the AT1-R blocker candesartan cilexetil (3 mg/kg) for 25 days. On days 12 and 14, the animals received an intraventricular injection of streptozotocin (3 mg/kg) each day. On day 25, they were tested for spatial, working, and declarative memory through the Morris water maze, holeboard, and novel object recognition tests, respectively. The oxidative stress marker, malondialdehyde, was measured in isolated brain microvessels. Cerebrospinal fluid was collected for tumor necrosis factor-α determination. The volume of the lateral ventricles was evaluated for morphological changes. The AT1-R blocker pretreatment prevented streptozotocin-induced declines in declarative and working memory. No changes in spatial and long-term memory were observed. Streptozotocin increased malondialdehyde in isolated microvessels and tumor necrosis factor-α levels, which were prevented by candesartan administration. All these findings are consistent with the involvement of AT1-R in early streptozotocin-induced changes, with behavioral and inflammatory/morphological outcomes likely mediated by overlapping yet partially distinct mechanisms.
SN - 1467-3045
SN - 1467-3037
ER -