Analysis of the Glymphatic System and Expression of Aquaporin 4 in Astrocytes of mice under Normal Chow and High Caloric Diet

Sherif Idriss, University of Lübeck

 

Aims

The discovery and characterization of the glymphatic system is quite recent; first described in 2012 (Iliff et al. 2012). The peripheral lymphatic vasculature is parallel to the blood vasculature and acts as a second circulation, clearing the intersterstitial fluid (ISF) with its constituent proteins and other solutes not absorbed across postcapillary venules. Undoubtedly, it is critical to both hydrostatic and homeostatic maintenance. The cerebrospinal fluid (CSF) of the central nervous system (CNS) formed in the choroid plexi, is thought be crucial in solute clearance from the brain. CSF flows through the cerebral ventricles and the subarachnoid space to its ultimate sites of reabsorption into the bloodstream via arachnoid villi of the dural sinuses, along cranial nerve sheaths or through the nasal lymphatics. Astroglial aquaporin-4 (AQP4) water channel is highly polarized to perivascular endfeet that bind the para-arterial CSF influx and the paravenous ISF clearance pathways. Animals lacking aquaporin 4 in astrocytes show a 70% reduction in interstitial solute clearance and slowed CSF influx through this system. This points to the fact that bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport.

The main aim of this collaborative project is to analyse the effect of high fat diet (HFD) on the expression and localisation of aquaporin 4 in whole mouse brains compared to mice under normal chow (NC).

 

Grant awarded: €2,000