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Open AccessArticle

Proteasome and Autophagy-Mediated Impairment of Late Long-Term Potentiation (l-LTP) after Traumatic Brain Injury in the Somatosensory Cortex of Mice

1
Institute for Physiology, UMC of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany
2
Institute for Pathobiochemistry, UMC of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany
3
Clinics for Anaesthesiology, UMC of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(12), 3048; https://doi.org/10.3390/ijms20123048
Received: 6 May 2019 / Revised: 17 June 2019 / Accepted: 19 June 2019 / Published: 21 June 2019
(This article belongs to the Special Issue Rhine-Main Neuroscience Network: rmn^2-Oberwesel 2018)
Traumatic brain injury (TBI) can lead to impaired cognition and memory consolidation. The acute phase (24–48 h) after TBI is often characterized by neural dysfunction in the vicinity of the lesion, but also in remote areas like the contralateral hemisphere. Protein homeostasis is crucial for synaptic long-term plasticity including the protein degradation systems, proteasome and autophagy. Still, little is known about the acute effects of TBI on synaptic long-term plasticity and protein degradation. Thus, we investigated TBI in a controlled cortical impact (CCI) model in the motor and somatosensory cortex of mice ex vivo-in vitro. Late long-term potentiation (l-LTP) was induced by theta-burst stimulation in acute brain slices after survival times of 1–2 days. Protein levels for the plasticity related protein calcium/calmodulin-dependent protein kinase II (CaMKII) was quantified by Western blots, and the protein degradation activity by enzymatical assays. We observed missing maintenance of l-LTP in the ipsilateral hemisphere, however not in the contralateral hemisphere after TBI. Protein levels of CaMKII were not changed but, interestingly, the protein degradation revealed bidirectional changes with a reduced proteasome activity and an increased autophagic flux in the ipsilateral hemisphere. Finally, LTP recordings in the presence of pharmacologically modified protein degradation systems also led to an impaired synaptic plasticity: bath-applied MG132, a proteasome inhibitor, or rapamycin, an activator of autophagy, both administered during theta burst stimulation, blocked the induction of LTP. These data indicate that alterations in protein degradation pathways likely contribute to cognitive deficits in the acute phase after TBI, which could be interesting for future approaches towards neuroprotective treatments early after traumatic brain injury. View Full-Text
Keywords: traumatic brain injury; long-term potentiation; plasticity related proteins; proteasome; autophagy, somatosensory cortex traumatic brain injury; long-term potentiation; plasticity related proteins; proteasome; autophagy, somatosensory cortex
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Feldmann, L.K.; Le Prieult, F.; Felzen, V.; Thal, S.C.; Engelhard, K.; Behl, C.; Mittmann, T. Proteasome and Autophagy-Mediated Impairment of Late Long-Term Potentiation (l-LTP) after Traumatic Brain Injury in the Somatosensory Cortex of Mice. Int. J. Mol. Sci. 2019, 20, 3048.

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