This preprint is under consideration at BMC Neuroscience. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Behavioral Sensitization Induced by Methamphetamine Causes Differential Alterations in Gene Expression and Histone Acetylation of the Prefrontal Cortex in Rats
Jin Li
Beijing institute of Pharmacology and Toxiology
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0866-5483
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats.
Methods: We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays.
Results: In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure.
Conclusions: The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.
Keywords
methamphetamine, behavioral sensitization, differentially expressed genes, histone acetylation, ANP32A, POU3F2
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 4
Posted 13 Jan, 2021
No community comments so far
Submission checks complete
On 05 Jan, 2021
Editorial decision: Minor revision
On 04 Jan, 2021
No comments provided
Review #1 received
Received 10 Aug, 2020
Reviewers invited
Invitations sent on 24 Jul, 2020
Reviewer #1 agreed
On 24 Jul, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
Editor invited
On 25 May, 2020
No comments provided
Editorial decision: Minor revision
On 13 May, 2020
Review #1 received
Received 07 Apr, 2020
Reviewer #1 agreed
On 28 Mar, 2020
Reviewers invited
Invitations sent on 25 Mar, 2020
Editor assigned
On 24 Mar, 2020
Submission checks complete
On 23 Mar, 2020
Editor invited
On 23 Mar, 2020
No comments provided
Editorial decision: Major revision
On 24 Feb, 2020
Review #1 received
Received 29 Jan, 2020
Review #2 received
Received 29 Jan, 2020
Reviewer #2 agreed
On 14 Jan, 2020
Reviewer #1 agreed
On 09 Jan, 2020
Reviewers invited
Invitations sent on 07 Jan, 2020
Editor assigned
On 03 Jan, 2020
Submission checks complete
On 02 Jan, 2020
Editor invited
On 02 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at BMC Neuroscience. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Behavioral Sensitization Induced by Methamphetamine Causes Differential Alterations in Gene Expression and Histone Acetylation of the Prefrontal Cortex in Rats
Jin Li
Beijing institute of Pharmacology and Toxiology
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0866-5483
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 4
Posted 13 Jan, 2021
No community comments so far
Submission checks complete
On 05 Jan, 2021
Editorial decision: Minor revision
On 04 Jan, 2021
No comments provided
Review #1 received
Received 10 Aug, 2020
Reviewers invited
Invitations sent on 24 Jul, 2020
Reviewer #1 agreed
On 24 Jul, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
Editor invited
On 25 May, 2020
No comments provided
Editorial decision: Minor revision
On 13 May, 2020
Review #1 received
Received 07 Apr, 2020
Reviewer #1 agreed
On 28 Mar, 2020
Reviewers invited
Invitations sent on 25 Mar, 2020
Editor assigned
On 24 Mar, 2020
Submission checks complete
On 23 Mar, 2020
Editor invited
On 23 Mar, 2020
No comments provided
Editorial decision: Major revision
On 24 Feb, 2020
Review #1 received
Received 29 Jan, 2020
Review #2 received
Received 29 Jan, 2020
Reviewer #2 agreed
On 14 Jan, 2020
Reviewer #1 agreed
On 09 Jan, 2020
Reviewers invited
Invitations sent on 07 Jan, 2020
Editor assigned
On 03 Jan, 2020
Submission checks complete
On 02 Jan, 2020
Editor invited
On 02 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats.
Methods: We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays.
Results: In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure.
Conclusions: The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6