Kaempferol Protects Against Amyloid β Overproduction and the Rise of Phospho-Tau 217 and Phospho-Tau 181 in the Rat Cerebellum Induced by Acute 3-Nitropropionic Acid Administration

The 3-nitropropionic acid (NPA) promotes neurological alterations in the striatum, hippocampus and vicinal motor and pre-motor cortical areas, and in the cerebellum. The neurological alterations induced by systemic NPA administration resemble those found in Huntington’s disease. In previous works, we have shown that intraperitoneal (i.p.) administration of kaempferol can efficiently protect against striatum degeneration and against motor neurological dysfunctions induced by NPA. In this work, we show that i.p. administration of kaempferol also protects against the increase of pro-inflammatory cytokines that potentiate the activation of complement C3 protein (a biomarker of A1-type reactive astrocytes generation) and overproduction of neurotoxic amyloid β (Aβ) peptides in the cerebellum of rats treated with acute i.p. administration of NPA. In NPA-treated rats, large multipolar neurons of cerebellar nuclei and Purkinje neurons of the cerebellar cortex are the cells most intensely stained by anti-C3 and by anti-Aβ antibodies. In addition, we found that kaempferol also protects against the NPA-induced increase of phospho-tau 217 and phospho-tau 181 in the cerebellum, and our results pointed out that the NPA-induced phospho-tau 217 colocalizes with Aβ(1-42) more closely than phospho-tau 181, both in dentate nucleus and cerebellar cortex. Also, our results unveil another novel brain protection action of i.p. kaempferol co-administration, namely, its ability to prevent microhemorrhages induced in the cerebellar nuclei area by acute NPA administration. In conclusion, our results lend strong support to its use in the therapeutic treatment of NPA intoxication and related β-amyloidopathies and tauopathies.