A novel squaramide compound alleviates cognitive deficits through activation of Akt and Erk1/2 in a rat model of vascular dementia.

Abstract

Vascular dementia is the second most common type of dementia, yet no effective treatment for it exists. Akt and Erk1/2 signaling pathways are involved in neuronal survival. It has been reported that bisperoxovanadium (pyridin-2-squaramide), a novel squaramide compound, protects against cerebral ischemia injury via activation of Akt and Erk1/2. Here, the potential neuroprotective effect of bisperoxovanadium is shown for the first time in a model of vascular dementia induced in 6-month-old male Sprague-Dawley rats by two-vessel occlusion injury applied to 6-month-old. Following this lesion, bisperoxovanadium (pyridin-2-squaramide) (1 mg/kg/day) was intragastrically administered for four successive weeks. The Morris water maze test estimated cognitive function. The morphological examination was performed by hematoxylin-eosin staining. Akt and Erk1/2 protein abundance were assessed by Western blot. Results showed that bisperoxovanadium (pyridin-2-squaramide) attenuated not only cognitive dysfunction but also alleviated histopathological changes in rats with vascular dementia. Moreover, bisperoxovanadium (pyridin-2-squaramide) ultimately reduced neuronal apoptosis represented by the Bax/Bcl-2 ratio in the CA1 (cornu ammonis 1) region of the hippocampus. Importantly, the levels of p-Akt(ser473) and p-Erk1/2(Thr202/Tyr204>) were increased after treatment with bisperoxovanadium (pyridin-2-squaramide). It is concluded that the novel squaramide compound bisperoxovanadium (pyridin-2-squaramide) might be effective in the treatment of vascular dementia by activation of Akt and Erk1/2.

• Authors: Meichun Yuan, Hezhong Zhu, Jiajuan Chen, Dan Zhao, Qi Wan, Zhifeng Zhang
• Journal: Journal of integrative neuroscience (J Integr Neurosci) Vol. 18 Issue 4 Pg. 401-408 (Dec 30 2019) ISSN: 0219-6352 [Print] Singapore
• PMID: 31912698 (Publication Type: Journal Article)
• Copyright: © 2019 Yuan et al. Published by IMR press.

Chemical References

• Neuroprotective Agents
• Vanadium Compounds
• bisperoxovanadium
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis (drug effects)
• Behavior, Animal (drug effects)
• CA1 Region, Hippocampal (drug effects)
• Cognitive Dysfunction (drug therapy, etiology)
• Dementia, Vascular (complications, drug therapy)
• Disease Models, Animal
• MAP Kinase Signaling System (drug effects)
• Male
• Maze Learning (drug effects)
• Neuroprotective Agents (administration & dosage, pharmacology)
• Proto-Oncogene Proteins c-akt (drug effects)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Vanadium Compounds (administration & dosage, pharmacology)