It is assumed that dysfunction of tanycytes could be one of the components of pathogenesis of both Alzheimer disease and type 2 diabetes mellitus. The study was aimed to assess alterations in the tanycyte morphology in the Alzheimer disease model. The 3 mg/kg streptozotocin dose was injected in the lateral ventricles of Wistar rats in order to model the Alzheimer disease. Alterations in hypothalamic tanycytes were assessed 2 weeks, 4 weeks, 3 months and 6 months after administration of the toxin. Immunohistochemistry was used to identify the protein markers of tanycytes (vimentin, nestin), astrocytes (GFAP, glutamine synthetase) and neurons (HuC/D), as well as to assess cell proliferation (with the use of Ki67 protein) and mitochondrial alterations (mitochondrial complex IV, PGC1a). Administration of streptozotocin lead to β-amyloid accumulation in hypothalamus and ventricular enlargement (p < 0.001). Streptozotocin damaged both α1/α2 tanycytes and β1 tanycytes. The intensity of vimentin staining in α1/α2 tanycytes decreased by week 4 (p = 0.003), and in β1 tanycytes it decreased in three months (p < 0.001). The same trend was observed for nestin. The number of Ki67+ nuclei decreased (p < 0.05), and the expression of proteins associated with mitochondria changed. The density of hypothalamic tanycytes decreased by week 4 after administration of the toxin. Moreover, astrocyte activation was revealed. However, no prominent damage to both astrocytes and neurons was observed within four weeks after administration of streptozotocin. The revealed high tanycyte vulnerability to streptozotocin is in line with the hypothesis of the role of damage to hypothalamic structures in both local and systemic metabolic disorders occurring in the Alzheimer disease models.
The role of cerebral amyloid accumulation in common forms of Alzheimer disease
