The neuroprotective function of 2-carba-cyclic phosphatidic acid: Implications for tenascin-C via astrocytes in traumatic brain injury

Mari Nakashima; Mari Gotoh; Kei Hashimoto; Misaki Endo; Kimiko Murakami-Murofushi; Hiroko Ikeshima-Kataoka; Yasunori Miyamoto

doi:10.1016/j.jneuroim.2021.577749

The neuroprotective function of 2-carba-cyclic phosphatidic acid: Implications for tenascin-C via astrocytes in traumatic brain injury

J Neuroimmunol. 2021 Dec 15:361:577749. doi: 10.1016/j.jneuroim.2021.577749. Epub 2021 Oct 9.

Authors

Mari Nakashima¹, Mari Gotoh², Kei Hashimoto³, Misaki Endo¹, Kimiko Murakami-Murofushi⁴, Hiroko Ikeshima-Kataoka⁵, Yasunori Miyamoto⁶

Affiliations

¹ Graduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Innovation, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan.
² Institute for Human Life Innovation, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Research division of human welfare science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan.
³ Institute for Human Life Innovation, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan.
⁴ Research division of human welfare science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan.
⁵ Faculty of Science and Engineering, Waseda University, Okubo, Shinjuku-ku, Tokyo, Japan. Electronic address: ikeshima@1988.jukuin.keio.ac.jp.
⁶ Graduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Innovation, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan. Electronic address: miyamoto.yasunori@ocha.ac.jp.

PMID: 34688067
DOI: 10.1016/j.jneuroim.2021.577749

Abstract

We examined the mechanism how 2-carba-cyclic phosphatidic acid (2ccPA), a lipid mediator, regulates neuronal apoptosis in traumatic brain injury (TBI). First, we found 2ccPA suppressed neuronal apoptosis after the injury, and increased the immunoreactivity of tenascin-C (TN-C), an extracellular matrix protein by 2ccPA in the vicinity of the wound region. 2ccPA increased the mRNA expression levels of Tnc in primary cultured astrocytes, and the conditioned medium of 2ccPA-treated astrocytes suppressed the apoptosis of cortical neurons. The neuroprotective effect of TN-C was abolished by knockdown of TN-C. These results indicate that 2ccPA contributes to neuroprotection via TN-C from astrocytes in TBI.

Keywords: 2-carba cyclic phosphatidic acid; Astrocyte; Lipopolysaccharide; Neuroprotection; Tenascin-C; Traumatic brain injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Astrocytes / drug effects
Astrocytes / metabolism*
Brain Injuries, Traumatic / drug therapy
Brain Injuries, Traumatic / metabolism*
Cells, Cultured
Cerebral Cortex / cytology
Culture Media, Conditioned / pharmacology
Female
Glial Fibrillary Acidic Protein / biosynthesis
Glial Fibrillary Acidic Protein / genetics
Injections, Intraperitoneal
Lipopolysaccharides / pharmacology
Mice
Mice, Inbred ICR
Neurons / drug effects
Neurons / pathology
Neuroprotective Agents / therapeutic use*
Phosphatidic Acids / pharmacology
Phosphatidic Acids / physiology*
Phosphatidic Acids / therapeutic use
RNA Interference
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Tenascin / antagonists & inhibitors
Tenascin / genetics
Tenascin / metabolism*
Wounds, Stab / drug therapy
Wounds, Stab / metabolism

Substances

2-carba-cyclic phosphatidic acid
Culture Media, Conditioned
Glial Fibrillary Acidic Protein
Lipopolysaccharides
Neuroprotective Agents
Phosphatidic Acids
RNA, Messenger
Tenascin
Tnc protein, mouse
glial fibrillary astrocytic protein, mouse