Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex Article Swipe
Pamela Prini
,
Francesco Rusconi
,
Erica Zamberletti
,
Marina Gabaglio
,
Federica Penna
,
Mauro Fasano
,
Elena Battaglioli
,
Daniela Parolaro
,
Tiziana Rubino
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1503/jpn.170082
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1503/jpn.170082
Background: Increasing cannabis consumption among adolescents, studies that link its early use with mental illnesses, and the political debate on cannabis legalization together call for an urgent need to study molecular underpinnings of adolescent brain vulnerability. The emerging role of epigenetic mechanisms in psychiatric diseases led us to hypothesize that epigenetic alterations could play a role in causes and subsequent development of the depressive/psychotic-like phenotype induced by adolescent, but not adult, Δ9-tetrahydrocannabinol (THC) exposure in female rats. Methods: We performed a time-course analysis of histone modifications, chromatin remodelling enzymes and gene expression in the prefrontal cortex of female rats after adolescent and adult THC exposure. We also administered a specific epigenetic drug (chaetocin) with THC to investigate its impact on THC-induced behavioural alterations. Results: Adolescent THC exposure induced alterations of selective histone modifications (mainly H3K9me3), impacting the expression of genes closely associated with synaptic plasticity. Changes in both histone modifications and gene expression were more widespread and intense after adolescent treatment, suggesting specific adolescent susceptibility. Adolescent THC exposure significantly increased Suv39H1 levels, which could account for the enhanced H3K9me3. Pharmacological blockade of H3K9me3 during adolescent THC treatment prevented THC-induced cognitive deficits, suggesting the relevant role played by H3K9me3 in THC-induced effects. Limitations: Only female rats were investigated, and the expression studies were limited to a specific subset of genes. Conclusion: Through a mechanism involving SUV39H1, THC modifies histone modifications and, thereby, expression of plasticity genes. This pathway appears to be relevant for the development of cognitive deficits.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1503/jpn.170082
- http://jpn.ca/wp-content/uploads/2018/02/43-2-87.pdf
- OA Status
- bronze
- Cited By
- 78
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2791633973
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2791633973Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1503/jpn.170082Digital Object Identifier
- Title
-
Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortexWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-02-27Full publication date if available
- Authors
-
Pamela Prini, Francesco Rusconi, Erica Zamberletti, Marina Gabaglio, Federica Penna, Mauro Fasano, Elena Battaglioli, Daniela Parolaro, Tiziana RubinoList of authors in order
- Landing page
-
https://doi.org/10.1503/jpn.170082Publisher landing page
- PDF URL
-
https://jpn.ca/wp-content/uploads/2018/02/43-2-87.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
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-
bronzeOpen access status per OpenAlex
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https://jpn.ca/wp-content/uploads/2018/02/43-2-87.pdfDirect OA link when available
- Concepts
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Epigenetics, Histone H3, Prefrontal cortex, Histone, Chromatin, Neuroscience, Neuroplasticity, Psychology, Biology, Cognition, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
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78Total citation count in OpenAlex
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2025: 8, 2024: 4, 2023: 17, 2022: 15, 2021: 7Per-year citation counts (last 5 years)
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55Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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