Back to Search
Start Over
The Effect of Allopregnanolone on Enzymatic Activity of the DNA Base Excision Repair Pathway in the Sheep Hippocampus and Amygdala under Natural and Stressful Conditions.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Oct 20; Vol. 21 (20). Date of Electronic Publication: 2020 Oct 20. - Publication Year :
- 2020
-
Abstract
- The neurosteroid allopregnanolone (AL) has many beneficial functions in the brain. This study tested the hypothesis that AL administered for three days into the third brain ventricle would affect the enzymatic activity of the DNA base excision repair (BER) pathway in the hippocampal CA1 and CA3 fields and the central amygdala in luteal-phase sheep under both natural and stressful conditions. Acute stressful stimuli, including isolation and partial movement restriction, were used on the last day of infusion. The results showed that stressful stimuli increased N-methylpurine DNA glycosylase (MPG), thymine DNA glycosylase (TDG), 8-oxoguanine glycosylase (OGG1), and AP-endonuclease 1 (APE1) mRNA expression, as well as repair activities for 1, N <superscript>6</superscript> -ethenoadenine (εA), 3, N <superscript>4</superscript> -ethenocytosine (εC), and 8-oxoguanine (8-oxoG) compared to controls. The stimulated events were lower in stressed and AL-treated sheep compared to sheep that were only stressed (except MPG mRNA expression in the CA1 and amygdala, as well as TDG mRNA expression in the CA1). AL alone reduced mRNA expression of all DNA repair enzymes (except TDG in the amygdala) relative to controls and other groups. DNA repair activities varied depending on the tissue-AL alone stimulated the excision of εA in the amygdala, εC in the CA3 and amygdala, and 8-oxoG in all tissues studied compared to controls. However, the excision efficiency of lesioned bases in the AL group was lower than in the stressed and stressed and AL-treated groups, with the exception of εA in the amygdala. In conclusion, the presented modulating effect of AL on the synthesis of BER pathway enzymes and their repair capacity, both under natural and stressful conditions, indicates another functional role of this neurosteroid in brain structures.
- Subjects :
- Amygdala enzymology
Amygdala metabolism
Animals
CA1 Region, Hippocampal enzymology
CA1 Region, Hippocampal metabolism
CA3 Region, Hippocampal enzymology
CA3 Region, Hippocampal metabolism
DNA Glycosylases genetics
DNA Glycosylases metabolism
DNA-(Apurinic or Apyrimidinic Site) Lyase genetics
DNA-(Apurinic or Apyrimidinic Site) Lyase metabolism
Female
RNA, Messenger genetics
RNA, Messenger metabolism
Sheep
Thymine DNA Glycosylase genetics
Thymine DNA Glycosylase metabolism
Amygdala drug effects
CA1 Region, Hippocampal drug effects
CA3 Region, Hippocampal drug effects
DNA Repair genetics
Gene Expression Regulation, Enzymologic drug effects
Pregnanolone pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33092287
- Full Text :
- https://doi.org/10.3390/ijms21207762