Lithium carbonate treatment decrease neuroinflammation and ameliorates long‐term memory in a Down syndrome animal model

Abstract

AbstractBackgroundIndividuals with Down Syndrome (DS) have an increased genetic risk for developing Alzheimer’s Disease (AD), due to a higher expression of genes related to the pathophysiological development of the disease and to the inflammatory process. Brain damage is already substantial when the first clinical signs of AD appear, it is essential to study therapeutic alternatives that delay its development. As lithium carbonate has been identified as a neuroprotective and neuroplastic agent in neurodegeneration, the aim of this study is to evaluate the treatment effect of lithium carbonate in the neuroinflammation and long‐term memory of Ts65Dn animal model of DS.MethodTs65Dn mice (trisomy confirmed by genotyping) were treated with a lithium carbonate microdose (0.25 mg/kg dissolved in water) for 18 months and compared to non‐treated animals. To evaluate the treatment, [11C]PK11195 PET images were acquired at the ages of 5, 14, 20 and 24 months. Whole brain images were quantified in SUV (Standardized Uptake Value) and long‐term memory was assessed by the novel object recognition test (1).Result[11C]PK11195 uptake was increased at 14 months in the non‐treated animals when compared to the respective age of 5 months (+29%), although not statistically significant. However, when mice were treated with lithium, this increase was not detected. Compared to 14 months, at the ages of 20 and 24 months, there was a decreased uptake in the non‐treated animals (Ts65Dn: ‐52%, p = 0.01 at 20 months; Ts65Dn: ‐59%, p = 0.006; at 24 months) and whereas in Ts65Dn‐lithium, the uptake did not change significantly among the ages. There was a decrease in the long‐term memory index in the non‐treated animals, at the ages of 20 (p = 0.03) and 24 months (p = 0.009), compared to 14 months‐old whereas in the treated animals the memory was preserved.ConclusionThe treatment with lithium carbonate prevented glial cells alterations during life‐span and preserved long‐term memory of a Down syndrome animal model indicating that this treatment can contribute to a healthy brain aging in this syndrome.