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 <i>striatum</i>, <i>hippocampus</i> and vicinal motor and pre-motor cortical areas, and in the <i>cerebellum</i>. 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 <i>striatum</i> 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 in 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 <i>cerebellum</i> of rats treated with acute i.p. administration of NPA. In NPA-treated rats, large multipolar neurons of cerebellar <i>nuclei</i> and Purkinje neurons of the cerebellar <i>cortex</i> are the cells that are most intensely stained by anti-C3 and by anti-Aβ antibodies. In addition, we found that kaempferol also protects against the NPA-induced increase in phospho-tau 217 and phospho-tau 181 in the <i>cerebellum</i>, 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 <i>nucleus</i> and cerebellar <i>cortex</i>. Also, our results unveil another novel brain-protective action of i.p. kaempferol co-administration: namely, its ability to prevent microhemorrhages induced in the cerebellar <i>nuclei</i> area by acute NPA administration. In conclusion, the results of this work show a potent protection of kaempferol against the NPA-induced increase in degeneration biomarkers in the <i>cerebellum</i>.