Minocycline reduces inflammatory parameters in the brain structures and serum and reverses memory impairment caused by the administration of amyloid β (1-42) in mice.
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of age-related dementia. Cognitive decline, beta-amyloid (Aβ) accumulation, neurofibrillary tangles, and neuroinflammation are the main pathophysiological characteristics of AD. Minocycline is a tetracycline derivative with anti-inflammatory properties that has a neuroprotective effect. The aim of this study was to evaluate the effect of minocycline on memory, neurotrophins and neuroinflammation in an animal model of AD induced by the administration of Aβ (1-42) oligomer. Male BALB/c mice were treated with minocycline (50mg/kg) via the oral route for a total of 17days, 24h after intracerebroventricular administration of Aβ (1-42) oligomer. At the end of this period, was performed the radial maze test, and 24h after the last minocycline administration, serum was collected and the cortex and hippocampus were dissected for biochemical analysis. The administration of minocycline reversed the memory impairment caused by Aβ (1-42). In the hippocampus, minocycline reversed the increases in the levels of interleukin (IL-1β), Tumor Necrosis Factor- alpha (TNF-α) and, IL-10 caused by Aβ (1-42). In the cortex, AD-like model increase the levels of IL-1β, TNF-α and, IL-4. Minocycline treatment reversed this. In the serum, Aβ (1-42) increased the levels of IL-1β and IL-4, and minocycline was able to reverse this action, but not to reverse the decrease of IL-10 levels. Minocycline also reversed the increase in the levels of Brain-derived neurotrophic factor (BDNF) in the hippocampus caused by Aβ (1-42), and reduced Nerve Growth Factor (NGF) increases in the total cortex. Therefore, our results indicate that minocycline causes improvements in the spatial memory, and cytokine levels were correlated with this effect in the brain it. Besides this, minocycline reduced BDNF and NGF levels, highlighting the promising effects of minocycline in treating AD-like dementia.
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Michelle Lima
ML
Garcez
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Francielle
F
Mina
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Tatiani
T
Bellettini-Santos
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Franciellen Gonçalves
FG
Carneiro
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Aline Pereira
AP
Luz
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Gustavo Luis
GL
Schiavo
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Matheus Scopel
MS
Andrighetti
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Maylton Grégori
MG
Scheid
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Renan Pereira
RP
Bolfe
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.. Electronic address: josiane.budni@unesc.net.
Josiane
J
Budni
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D057967:Infusions, Intraventricular; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D015847:Interleukin-4 / Q000097:blood / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D016753:Interleukin-10; D015847:Interleukin-4; D008911:Minocycline
Alzheimer's disease; Minocycline; Neuroinflammation; Neurotrophins; Spatial memory