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Cerebellar ataxia is a heterogeneous group of neural disorders clinically characterized by cerebellar dysfunction. The diagnosis of patients with progressive cerebellar ataxia is complex due to the direct correlation with other neuron diseases. Although there is still no cure for this pathological condition, some metabolic, hereditary, inflammatory, and immunological factors affecting cerebellar ataxia are being studied and may become therapeutic targets. Advances in studying the neuroanatomy, pathophysiology, and molecular biology of the cerebellum (CE) contribute to a better understanding of the mechanisms behind the development of this disorder. In this study, Wistar rats aged 30 to 35 days were injected intraperitoneally with 3-acetylpyridine (3-AP) and/or metformin (for AMP-activated protein kinase (AMPK) enzyme activation) and euthanized in 24 hours and 4 days after injection. We analyzed the neuromodulatory role of the AMPK on cerebellar ataxia induced by the neurotoxin 3-AP in the brain stem (BS) and CE, after pre-treatment for 7 and 15 days with metformin, a pharmacological indirect activator of AMPK. The results shown here suggest that AMPK activation in the BS and CE leads to a significant reduction in neuroinflammation in these regions. AMPK was able to restore the changes in fatty acid composition and pro-inflammatory cytokines caused by 3-AP, suggesting that the action of AMPK seems to result in a possible neuroprotection on the cerebellar ataxia model., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Malaria is a major parasitic disease of humans and is a health public problem that affects more than 100 countries. In 2017, it caused nearly half a million deaths out of 219 million infections. Malaria is caused by the protozoan parasites of the genus Plasmodium and is transmitted by female mosquitoes of the genus Anopheles. Once in the bloodstream, Plasmodium merozoites invade erythrocytes and proliferate until the cells lyses and release new parasites that invade other erythrocytes. Remarkably, they can manipulate the vertebrate host's lipid metabolism pathways, since they cannot synthesize lipid classes that are essential for their development and replication. In this study, we show that mice infected with Plasmodium chabaudi present a completely different plasma profile from control mice, with marked hyperproteinemia, hypertriglyceridemia, hypoglycemia, and hypocholesterolemia. In addition, white adipose and hepatic tissue and analyses from infected animals revealed the accumulation of triacylglycerol in both tissues and free fatty acids and free cholesterol in the liver. Hepatic mRNA and protein expression of key enzymes and transcription factors involved in lipid metabolism were also altered by P. chabaudi infection, leading to a lipogenic state. The enzyme 5' AMP-activated protein kinase (AMPK), a master regulator of cell energetic metabolism, was also modulated by the parasite, which reduced AMPK phosphorylation levels upon infection. Pretreatment with metformin for 21 days followed by infection with P. chabaudi was effective in preventing infection of mice and also lowered the hepatic accumulation of lipids while activating AMPK. Together, these results provide new and important information on the specific molecular mechanisms induced by the malaria parasite to regulate hepatic lipid metabolism in order to facilitate its development, proliferation, and lifespan in its vertebrate host.