General anaesthesia leads to phosphoproteome changes in proteins involved in cytoskeleton remodelling and synaptic processes in the supraoptic nucleus of the hypothalamus

ABSTRACT: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia and natural sleep. Posttranslational modifications of proteins, including changes in phosphorylation, enable fast modulation of protein function which could be underlying the rapid effects of general anaesthesia. In order to identify potential phosphorylation events in the brain mediating general anaesthesia effects, we have explored the phosphoproteome responses in the rat SON, and compared these to cingulate cortex (CC) which displays no FOS activation is response to general anaesthetics. We found many changes in the phosphoproteomes of both the CC and SON in response to 15 minutes of isoflurane exposure. Pathway analysis indicated that proteins undergoing phosphorylation adaptations are involved in cytoskeleton remodelling and synaptic signalling events. Importantly, changes in protein phosphorylation appeared to be brain region-specific suggesting that differential phosphorylation adaptations might underlie the different neuronal activity responses to general anaesthesia between the CC and SON. In summary, these data suggest that rapid posttranslational modifications in proteins involved in cytoskeleton remodelling and synaptic signalling events might mediate the central mechanisms mediating general anaesthesia.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Benjamin Gillard  

LAB HEAD: David Murphy

PROVIDER: PXD039391 | Pride | 2024-01-23

REPOSITORIES: Pride