Detection of adiponectin in cerebrospinal fluid in humans

Abstract

Adiponectin circulates in the body in high concentrations, and 100-fold lower amounts were described in the cerebrospinal fluid (CSF) of mice, whereas in humans, contradictory results have been published. To clarify whether adiponectin is present in human CSF and is derived from the circulation, it was determined in human CSF and plasma of 52 nonselected patients. Adiponectin was detected by immunoblot in CSF and was quantified in CSF and serum by ELISA. CSF adiponectin was positively correlated to systemic levels, and the CSF/serum adiponectin ratio was correlated to the CSF/serum albumin ratio. Furthermore, disturbed function of the blood-brain barrier (BBB) was associated with an elevated CSF/serum adiponectin ratio. Adiponectin mRNA was not found in the brain, indicating that adiponectin crosses the BBB and/or the blood-cerebrospinal fluid barrier (BCB). Rat adiponectin with a COOH-terminal tag was injected into the tail vein of rats and was detected 3 h later in CSF. However, CSF adiponectin in humans and rats was approximately 0.1% of the serum concentration and therefore was below the 0.5% expected in the CSF because of the residual leakage of an undisturbed BBB/BCB. Taken together, data from the present study show that adiponectin in human CSF is far below the level expected by the baseline BBB/BCB permeability, indicating that adiponectin enters the brain much less efficiently than albumin, thus supporting recent data that exclude adiponectin transport to the CSF. Additional studies are needed to reveal whether these low levels of adiponectin in CSF have a physiological function.

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

“…1H; P < 0.005). This result further confirmed that LMW adiponectin could enter the CNS from the circulation (30).…”

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

“…Recent studies suggest that different multimeric forms of adiponectin can influence its ability to pass the blood-brain barrier and its biological activity (14)(15)(16)(17). Next, we examined the effects of social-defeat stress on the distribution of oligomeric complexes of adiponectin using gel filtration chromatography followed by immunoblotting.…”

“…Full-length adiponectin is the predominant circulating form and can be found as a trimer, hexamer, or high molecular weight (HMW) oligomer (10,12), whereas globular adiponectin exists as a trimer (13). Evidence shows that adiponectin enters the brain from circulation (14)(15)(16)(17). Intraventricular (i.v.)…”

“…Intraventricular (i.v.) injection of adiponectin leads to a rise in cerebrospinal fluid (CSF) adiponectin levels in mice and rats (15,18), and trimeric and hexameric forms of adiponectin are detected in the CSF of adiponectin knockout mice after i.v. injection (16).…”

Adiponectin protects rat hippocampal neurons against excitotoxicity

“…Further post hoc test (Student-Newman-Keuls) indicated that the adiponectin group was significantly different from other three groups (p<0.01) tration of adiponectin also reduces serum glucose and lipid levels (Qi et al 2004). Existing data on blood brain barrier permeability to peripheral adiponectin remains equivocal, but it is clear that adiponectin is present in the brain parenchyma and cerebrospinal fluid Neumeier et al 2007;Pan and Kastin 2007).…”