Melatonin reduces β-amyloid accumulation and improves short-term memory in streptozotocin-induced sporadic Alzheimer's disease model

Marcos K Andrade; Leonardo C Souza; Evellyn M Azevedo; Ellen L Bail; Silvio M Zanata; Roberto Andreatini; Maria A B F Vital

doi:10.1016/j.ibneur.2023.01.005

Melatonin reduces β-amyloid accumulation and improves short-term memory in streptozotocin-induced sporadic Alzheimer's disease model

IBRO Neurosci Rep. 2023 Jan 26:14:264-272. doi: 10.1016/j.ibneur.2023.01.005. eCollection 2023 Jun.

Authors

Marcos K Andrade¹, Leonardo C Souza¹, Evellyn M Azevedo^{2

3}, Ellen L Bail^{2

3}, Silvio M Zanata³, Roberto Andreatini¹, Maria A B F Vital¹

Affiliations

¹ Department of Pharmacology, Federal University of Paraná, PR, Brazil.
² Department of Physiology, Federal University of Paraná, PR, Brazil.
³ Department of Basic Pathology, Federal University of Paraná, PR, Brazil.

Abstract

Melatonin is a hormone secreted by the pineal gland, it can be associated with circadian rhythms, aging and neuroprotection. Melatonin levels are decreased in sporadic Alzheimer's disease (sAD) patients, which suggests a relationship between the melatonergic system and sAD. Melatonin may reduce inflammation, oxidative stress, TAU protein hyperphosphorylation, and the formation of β-amyloid (Aβ) aggregates. Therefore, the objective of this work was to investigate the impact of treatment with 10 mg/kg of melatonin (i.p) in the animal model of sAD induced by the intracerebroventricular (ICV) infusion of 3 mg/kg of streptozotocin (STZ). ICV-STZ causes changes in the brain of rats similar to those found in patients with sAD. These changes include; progressive memory decline, the formation of neurofibrillary tangles, senile plaques, disturbances in glucose metabolism, insulin resistance and even reactive astrogliosis characterized by the upregulation of glucose levels and glial fibrillary acidic protein (GFAP). The results show that ICV-STZ caused short-term spatial memory impairment in rats after 30 days of STZ infusion without locomotor impairment which was evaluated on day 27 post-injury. Furthermore, we observed that a prolonged 30-day treatment with melatonin can improve the cognitive impairment of animals in the Y-maze test, but not in the object location test. Finally, we demonstrated that animals receiving ICV-STZ have high levels of Aβ and GFAP in the hippocampus and that treatment with melatonin reduces Aβ levels but does not reduce GFAP levels, concluding that melatonin may be useful to control the progression of amyloid pathology in the brain.

Keywords: AD, Alzheimer Disease; APP, Amyloid precursor protein; Alzheimer's disease; Aβ, β-amyloid; GFAP; GFAP, Glial fibrillary acidic protein; ICV-STZ, Intracerebroventricular injection of streptozotocin; MEL, Melatonin; MT1, Melatonin Receptor 1; MT2, Melatonin Receptor 2; Melatonin; OLT, Object location test; STZ, Streptozotocin; Short-term memory; Streptozotocin; TNF-α, Tumor Necrosis factor alpha; Y maze; sAD, Sporadic Alzheimer disease; β-amyloid.