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Published on: January 4, 2018
Fate of leptin after intracerebroventricular injection into the mouse brain
L M Maness1, A J Kastin, C L Farrell
1Veterans Affairs Medical Center and Tulane University School of Medicine, New Orleans, Louisiana 70112-1262, USA. lmaness@mailhost.tcs.tulane.edu
Insights
Intracerebroventricular administration of leptin (a metabolic regulator) showed it remains largely intact in the brain and cerebrospinal fluid. Leptin enters the bloodstream intact, reaching levels comparable to intravenous injection.
Area of Science:
- Neuroscience
- Endocrinology
- Metabolism
Background:
- Leptin is a key metabolic regulatory protein.
- Understanding leptin's fate after direct brain administration is crucial for neurological and metabolic research.
Purpose of the Study:
- To investigate the stability and distribution of leptin following intracerebroventricular (i.c.v.) administration in the brain.
- To determine leptin's efflux pathway from the brain into the bloodstream.
Main Methods:
- Radioiodinated leptin was administered intracerebroventricularly into the lateral ventricle of the brain.
- Brain and blood samples were analyzed for intact leptin levels over time.
- Autoradiography and computer-assisted image analysis were used to assess leptin distribution and penetration.
Main Results:
- 72% of recovered leptin remained intact in the brain after i.c.v. administration.
- Leptin efflux from the brain occurred with cerebrospinal fluid reabsorption, with 71% remaining intact in the blood.
- Leptin concentrations in the blood rose slowly, reaching levels comparable to intravenous administration within 20 minutes.
- Leptin showed slow disappearance from the ventricular system and limited periventricular penetration.
Conclusions:
- Intracerebroventricular leptin administration results in largely intact protein within the brain and its subsequent entry into circulation.
- The findings suggest leptin receptors may be present at the blood-cerebrospinal fluid barrier and within cerebral arteries.
Abstract:
The fate of the metabolic regulatory protein leptin was studied after intracerebroventricular (i.c.v.) administration into the lateral ventricle of the brain. In the brain, a mean of 72% of the recovered radioiodinated leptin was intact. Efflux from the brain for leptin occurred with the reabsorption of the cerebrospinal fluid into the blood. Leptin appearing in the blood was 71% intact over the course of the study. The amount of leptin in the blood rose slowly, and 20 min after i.c.v. injection equaled or exceeded levels previously seen 20 min after i.v. administration. Autoradiography showed the slow disappearance of leptin from the ventricular system over time. The degree of periventricular penetration of radiolabeled leptin also was determined. By 30 min, leptin was detected 600 microm from the midline, but computer-assisted image analysis showed that the amount of radioactivity had fallen to half the midline value by 300 microm. The concentration of leptin within the arcuate nucleus, previously observed after i.v. administration, was not seen after i.c.v. injection. High concentrations of leptin were found at the choroid plexus, suggesting the presence of leptin receptors on the brain side of the blood-cerebrospinal fluid barrier and within the lumen of the middle cerebral arteries.
