Analysis of the regulatory mechanisms that affect Gpm6a expression levels in the hippocampus of chronically stressed rats

JEZOVA, D.; ALZURI, S.E.; HLAVACOVA, N.; FUCHSOVA, B.

Córdoba

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN) 2018; 2018

SAN

Analysis of the regulatory mechanisms that affect Gpm6a expression levels in the hippocampus of chronically stressed ratsAlzuri S.E., Hlavacova N.*,Jezova D.*, Fuchsova B. Instituto de Investigaciones Biotecnológicas (IIB-INTECH, UNSAM, CONICET), San Martin, Buenos Aires, Argentina*Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia The neuronal membrane glycoprotein M6a (Gpm6a) is a member of myelin proteolipid protein (PLP/DM20) family that functions in the processes of neuronal remodeling and plasticity, such as neurite outgrowth, filopodium formation, and synaptogenesis. Pathological conditions have been linked to the alterations in Gpm6a expression levels or sequence. Downregulation of Gpm6a mRNA has been shown in the hippocampus of depressed suicide victims as well as in animal models of chronic stress. Regulatory mechanisms that affect Gpm6a expression levels during chronic stress exposure and in pathological conditions are not clearly understood.Different epigenetic mechanisms have been described to regulate Gpm6a mRNA levels: i) direct posttranscriptional regulation by miR-133b or ii) by miR-124, as well as iii) transcriptional regulation through miR-124 and miR-9 mediated effect on Hdac5-regulated transcriptional factor Mef2c. Here, we use qPCR to demonstrate that in the hippocampus of chronically stressed rats, the exposure to restraint stress decreases levels of Gpm6a mRNA as well as the expression levels of miR-133b, miR-124a, but not miR-9-5p. Moreover, we detect altered levels of Hdac5 and Mef2c suggesting that chronic stress affects Gpm6a levels through miR-124 mediated effect on Hdac5 and Mef2c. Overexpression of miR-124 in cultured hippocampal neurons leads to increased neuronal arborization as assessed by Sholl analysis and increases Gpm6a protein levels.  <!-- /* Font Definitions */@font-face{font-family:Times;panose-1:2 0 5 0 0 0 0 0 0 0;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:"ＭＳ 明朝";mso-font-charset:78;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1791491579 18 0 131231 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-520092929 1073786111 9 0 415 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073743103 0 0 415 0;}@font-face{font-family:ArialMT;panose-1:0 0 0 0 0 0 0 0 0 0;mso-font-alt:Arial;mso-font-charset:77;mso-generic-font-family:swiss;mso-font-format:other;mso-font-pitch:auto;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:10.0pt;margin-left:0cm;mso-pagination:widow-orphan;font-size:12.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:JA;}h1{mso-style-priority:9;mso-style-unhide:no;mso-style-qformat:yes;mso-style-link:"Título 1 Car";mso-margin-top-alt:auto;margin-right:0cm;mso-margin-bottom-alt:auto;margin-left:0cm;mso-pagination:widow-orphan;mso-outline-level:1;font-size:24.0pt;font-family:Times;mso-bidi-font-family:"Times New Roman";mso-fareast-language:EN-US;}span.Ttulo1Car{mso-style-name:"Título 1 Car";mso-style-priority:9;mso-style-unhide:no;mso-style-locked:yes;mso-style-link:"Título 1";mso-ansi-font-size:24.0pt;mso-bidi-font-size:24.0pt;font-family:Times;mso-ascii-font-family:Times;mso-hansi-font-family:Times;mso-bidi-font-family:"Times New Roman";mso-font-kerning:18.0pt;mso-fareast-language:EN-US;font-weight:bold;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:JA;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:10.0pt;}@page WordSection1{size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->