Aim
Glial fibrillary acidic protein (GFAP) molecularly associates with aquaporin 4 (AQP4) in astrocytic plasticity. Here, we further examined how AQP4 modulates osmotic effects on vasopressin (VP) neurons in rat supraoptic nucleus (SON) through interactions with GFAP in astrocytes.
Conclusion
These findings indicate that osmotically driven increase in VP neuronal activity requires the activation of AQP4, which determines a retraction of GFAP filaments.
Methods
Brain slices from adult male rats were kept under osmotic stimulation. Western blot, co-immunoprecipitation, immunohistochemistry and patch-clamp recordings were used for analysis of expressions and interactions between GFAP and AQP4, astrocyte-specific proteins in the SON, as well as their influence on VP neuronal activity. Data were analysed using SPSS software.
Results
Hyposmotic challenge (HOC) of acute SON slices caused an early (within 5 minutes) and transient increase in the colocalization of AQP4 with GFAP filaments. This effect was prominent at astrocytic processes surrounding VP neuron somata and was accompanied by inhibition of VP neuronal activity. Similar HOC effect was seen in the SON isolated from rats subjected to in vivo HOC, wherein a transiently increased molecular association between GFAP and AQP4 was detected using co-immunoprecipitation. The late stage rebound excitation (10 minutes) of VP neurons in brain slices subjected to HOC and the associated astrocytic GFAP's 'return to normal' were both hampered by 2-(nicotinamide)-1,3,4-thiadiazole, a specific AQP4 channel blocker that itself did not influence VP neuronal activity. Moreover, this agent prevented hyperosmotic stress-evoked excitation of VP neurons and associated reduction in GFAP filaments.