The role of the CBS/H2S pathway in the brain during hibernation.

Bruintjes, J. (Jojanneke) (2013) The role of the CBS/H2S pathway in the brain during hibernation. thesis, Medicine.

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Abstract

Small endothermic mammals use hibernation as a survival strategy in periods with unreliable food availability and low ambient temperature. Hibernation consists of torpor phases, during which metabolism is severely depressed and body temperature (Tb) extremely reduced. The torpor phases are alternated with brief periods of restoration of metabolism and euthermia, called arousals. Remarkably, hibernating animals do not develop organ damage during the repetitive cooling-rewarming cycles. The CBS/H2S pathway is coined as one of the underlying mechanisms, as H2S protects cells from damage and can also induce artificial torpor (also known as "suspended animation"). Because of lack of information about the regulation of the CBS/H2S pathway in the brain, this is an interesting subject to study, particularly in face of the possible protective effects of H2S. To this end, brain CBS expression was studied in natural hibernators (Syrian hamsters and Djungarian hamsters) and in pharmacologically induced torpor (by 5' adenosine monophosphate, in mice). Syrian hamsters were sacrificed in different stages of natural hibernation (euthermic, torpor early, torpor late and arousal late). The Djungarian hamsters and the mice were sacrificed in either torpor or euthermic conditions. CBS expression was studied by immunohistochemistry (IHC) and western blot (WB). In all animal species a distinctive expression pattern of CBS was found, mainly in the (pre-frontal) cortex, hippocampus and thalamus. In Syrian hamster IHC stainings showed increased expression levels of CBS in the retrosplenial cortex of arousal late animals, compared to animals in other stages of hibernation. No distinctive differences in expression levels or expression patterns of CBS were found in the Djungarian hamsters or in the mice. From these data we conclude: - CBS has a distinctive and similar distribution pattern in brain of both hamster species and in mouse brain. Expression was mainly found in the (pre-frontal) cortex, hippocampus and thalamus. - There is a clear difference between regulation in the arousal phase in natural hibernation and in 5'AMP induced "hibernation". This particularly concerns the retrosplenial cortex. The main role of the retrosplenial cortex is spatial navigation and episodic memory. The upregulation of CBS in this area during the arousal late phase can implicate higher necessity for its product, H2S. H2S can function as a protective agent, making sure the ability of these animals to navigate through the surroundings after arousal is maintained. Alternatively, H2S may act as a gasotransmitter, again helping arousing animals navigate through their environment to find the nearest food source.

Item Type:	Thesis (Thesis)
Supervisor name:	Henning, prof. dr. R.H. and Zee, prof.dr. E.A. van der
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:43
Last Modified:	25 Jun 2020 10:43
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/480

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