Morin post-treatment confers neuroprotection in a novel rat model of mild repetitive traumatic brain injury by targeting dementia markers, APOE, autophagy and Wnt/β-catenin signaling pathway.

Authors:
Ayman A Soubh
Ayman A Soubh
October 6 University
Egypt
Azza S Awad
Azza S Awad
Al-Azhar University (Girls)
Hanan S El-Abhar
Hanan S El-Abhar
Cairo University
Egypt

Brain Res 2019 Aug 16;1717:104-116. Epub 2019 Apr 16.

Department of Pharmacology & Toxicology, Cairo University, Cairo, Egypt.

Exposure to repetitive brain trauma has gained attention for its similarity to sport-related trauma. The traumatic brain injury (TBI) is strongly associated with neurodegenerative pathology that affects cognition, memory and behavior. The current study developed a novel mild repetitive traumatic brain injury (mRTBI) model to highlight some of the possible molecular pathological mechanisms compared to those of single trauma. Additionally, the study investigated the potential post-traumatic neuroprotective effect of Morin and/or MK-801. mRTBI was induced by weight drop model once daily for 5 days using Sprague-Dawley male rats. Animals were classified into control, mild TBI, mRTBI-5, mRTBI-7, mRTBI-5+DMSO, mRTBI-5+DMSO, mRTBI-5+Morin, mRTBI-5+MK801, and mRTBI-5+Morin+MK801. All treatments, especially the combination regimen, abated the cortical contents/protein expression of dementia markers (APO-E, Aβ, p(thr231)Tau, and p(Ser33)β-catenin), inflammatory markers (p(Ser536)NF-κBp65, and TNF-α, IL-6), and caspase-3 activity. Moreover, treatments enhanced the protein expression of Wnt-1 and autophagy-related markers (LC3BII/I and Beclin-1), besides the tissue content of the anti-apoptotic marker Bcl-2. These results entailed an improvement in the behavioral outcome, histological structure, and neuronal survival. In conclusion, the study proved that mRTBI impairs memory and alters APO-E/Aβ/p(thr231)Tau via the modulation of Wnt/β-catenin trajectory, autophagy, apoptosis, and inflammation. Additionally, post-treatment with Morin and/or MK-801 ameliorated these alterations, especially the combined regimen. It is also worth mentioning that Morin alone showed the finest behavioral improvements relative to the normal group. These results are summarized in Fig. 1.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S00068993193018
Publisher Site
http://dx.doi.org/10.1016/j.brainres.2019.04.003DOI Listing
August 2019
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