Expression of klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood

Abstract

Without the age-regulating protein klotho, mouse lifespan is shortened and the rapid onset of age-related disorders occurs. Conversely, overexpression of klotho extends mouse lifespan. Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus. Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development. We used in situ hybridization to map klotho mRNA expression in the developing and adult rat brain and report moderate, widespread expression across grey matter regions. mRNA expression levels in cortex, hippocampus, caudate putamen, and amygdala decreased during the second week of life and then gradually rose to adult levels by postnatal day 21. Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain. Klotho protein co-localized with both the neuronal marker NeuN, as well as, oligodendrocyte marker olig2. These results provide the first anatomical localization of klotho mRNA and protein in rat brain parenchyma and demonstrate that klotho levels vary during early postnatal development.

The Neuroprotective Effect of Klotho is Mediated via Regulation of Members of the Redox System

“…Once genotype results were obtained, hippocampi from KL-OE or WT were separately pooled, and neurons cultured to examine the effect of endogenous Klotho overexpression on neuronal survival. Klotho protein was detected on postnatal day 1 in the developing WT brain (54), and here we have detected Klotho at E18 with an increase in Klotho protein levels in whole brain lysates from KL-OE embryos as compared with WT embryos (Fig. 7A).…”

Klotho and fibroblast growth factor 23 in cerebrospinal fluid in children

“…Klotho, primarily identified as an anti-aging factor, is a 130 kDa singlepass, transmembrane protein belonging to the family of 1 glycosidase [15]. The expression of the Klotho gene has been found in the parathyroid glands, renal tubules, and at the apical plasma membrane of ependymal cells in the choroids plexus of both the lateral ventricles and the third ventricle [16][17][18][19]. Klotho protein forms constitutive binary complexes with several FGFR isoforms (FGFR1c, 3c, 4), and significantly increases the affinity of FGFRs to FGF23 [20].…”

Development and Characterization of Monoclonal Antibodies to Detect Klotho

“…(16)(17)(18) However, detection of KL at lower levels of expression is complex, even when mRNA is readily detectable. (19) As well, although KM2076 is robust via Western blot, its ability to work in immunohistochemistry (IHC) varies across laboratories. Antibody AF1819 detects only murine KL and appears to be the best option for detection of KL by IHC, revealing highly specific staining of KL in wild-type but not knockout tissues.…”