MAPKs are differentially modulated in arctic ground squirrels during hibernation

Area of Science:

• Neuroscience
• Comparative Physiology
• Molecular Biology

Background:

• Hibernating animals exhibit remarkable tolerance to central nervous system trauma.
• Arctic ground squirrels (AGS) face severe hypoxia and altered cerebral blood flow during arousal from hibernation.
• Sustained HIF1alpha elevation in euthermic AGS suggests a preparatory neuroprotective gene expression program.

Purpose of the Study:

• To investigate neuroprotective adaptations in AGS during hibernation and arousal.
• To examine the role of intracellular MAPK pathways in response to hypoperfusion/reperfusion.
• To understand the correlation between MAPK activation, HIF1alpha, and inflammation.

Main Methods:

• Analysis of intracellular MAPK pathways (ERK, JNK, p38) in AGS during hibernation, euthermia, and arousal.
• Measurement of HIF1alpha levels.
• Assessment of inducible nitric oxide synthase (iNOS) induction.

Main Results:

• ERK and JNK activation correlated positively with HIF1alpha levels in euthermic and aroused AGS.
• p38 activation was observed in euthermic AGS but attenuated in aroused AGS.
• p38 activation strongly correlated with iNOS induction, which was reduced in hibernating and aroused states.

Conclusions:

• Differential modulation of MAPK pathways (ERK, JNK, p38) is critical for AGS neuroprotection during hibernation.
• HIF1alpha-associated ERK and JNK activation likely mediate neuroprotection.
• Attenuation of p38 and iNOS contributes to reduced inflammation, enhancing neuroprotection during hibernation and arousal.