title: 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.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Clinton
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Glover
authors.forename: Astha
authors.initials: A
authors.lastname: Maltare
authors.forename: Ann M
authors.initials: AM
authors.lastname: Laszczyk
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Mehi
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Simmons
authors.forename: Gwendalyn D
authors.initials: GD
authors.lastname: King
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D000090265:Klotho Proteins; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000717428:Fgf23 protein, mouse; D012333:RNA, Messenger; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Aging; CSF; DAB; FGF23; FGFR; GFAP; ICC; IGF-1; IHC; In situ hybridization; Kl; MBP; Neurodevelopment; P; TGFβ; cerebrospinal fluid; diamino-benzidine; fibroblast growth factor 23; fibroblast growth factor receptor; glial fibrillary acidic protein; immunocytochemistry; immunohistochemistry; insulin-like growth factor 1; klotho; mRNA; messenger ribonucleic acid; myelin basic protein; postnatal; qPCR; quantitative polymerase chain reaction; transforming growth factor receptor beta