The Effects of Histone Deacetylase Inhibition on the Levels of Cerebral Cytokines in an Animal Model of Mania Induced by Dextroamphetamine
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Studies have suggested the involvement of inflammatory processes in the physiopathology of bipolar disorder. Preclinical evidences have shown that histone deacetylase inhibitors may act as mood-stabilizing agents and protect the brain in models of mania and depression. The aim of the present study was to evaluate the effects of sodium butyrate (SB) and valproate (VPA) on behavioral changes, histone deacetylase activity, and the levels of cytokines in an animal model of mania induced by dextroamphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for a period of 14 days, and then, between the 8th and 14th days, the rats were treated with SB, VPA, or Sal. The activity of histone deacetylase and the levels of cytokines (interleukin (IL) IL-4, IL-6, and IL-10 and tumor necrosis factor-alpha (TNF-α)) were evaluated in the frontal cortex and striatum of the rats. The administration of d-AMPH increased the activity of histone deacetylase in the frontal cortex. Administration of SB or VPA decreased the levels of histone deacetylase activity in the frontal cortex and striatum of rats. SB per se increased the levels of cytokines in both of the brain structures evaluated. AMPH increased the levels of cytokines in both of the brain structures evaluated, and VPA reversed this alteration. The effects of SB on d-AMPH-induced cytokine alterations were dependent on the brain structure and the cytokine evaluated. Despite VPA and SB having a similar mechanism of action, both…
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The modulation of LDX involves dopaminergic and adrenergic neurotransmission, inducing upregulation of ADRA2A, ADRA2B, ADRA2C, DRD1 and DRD5, and immunomodulation by modulating several interleukins, mainly IL-4 and IL-10 that present an anti-inflammatory profile.
“The modulation of LDX involves dopaminergic and adrenergic neurotransmission, inducing upregulation of ADRA2A, ADRA2B, ADRA2C, DRD1 and DRD5 [155, 158, 159], and immunomodulation by modulating several interleukins, mainly IL-4 and IL-10 that present an anti-inflammatory profile [160].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [160]
LDX modulates inflammation mediators such as TNF, IL-4, IL-6 and IL-10.
“Furthermore, LDX has been reported to modulate several inflammation mediators such as TNF, IL-4, IL-6 and IL-10 [160].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [160]
LDX increased pro-inflammatory cytokines TNFα and IL-6, and also anti-inflammatory cytokines IL-4 and IL-10 in the frontal cortex, striatum and serum in animal models of bipolar disorder.
“It has been assessed in ADHD comorbid disease, such as bipolar disorder in animal models [160], in which LDX increased the pro-inflammatory cytokines TNFα and IL-6, and also the anti-inflammatory cytokines IL-4 and IL-10 in the frontal cortex, striatum and serum [160, 198].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [160]
LDX promotes the activation of pro-inflammatory cytokines such as TNFα and IL-6, although it also promotes the expression of the anti-inflammatory cytokines IL-4 and IL-10 in the frontal cortex, striatum and serum.
“LDX promotes the activation of pro-inflammatory cytokines such as TNFα and IL-6, although it also promotes the expression of the anti-inflammatory cytokines IL-4 and IL-10 in the frontal cortex, striatum and serum.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [160]
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Behavioral and neurochemical effects of sodium butyrate in an animal model of mania
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“induces the over production of reactive oxygen species (ROS), increasing protein, lipid, and DNA oxidative damage in the brain of rats [31, 60, 61], which can lead to subsequent”
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Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“MAPK3 can induce the expression of some antiinflammatory cytokines (e.g. IL-2, IL-10), downregulated in patients with ADHD, via NFjB (NFKB1) activation [200–202].”
BackgroundInfluential
- Authors
- Valvassori, S. S., Resende, W. R., Varela, R. B., Arent, C. O., Gava, F. F., Peterle, B. R., Dal-Pont, G. C., Carvalho, A. F., Andersen, M. L., & Quevedo, J.
- Affiliations
- Universidade do Extremo Sul Catarinense (BR)
- Hospital de Clínicas de Porto Alegre (BR)
- Corresponding author
- Valvassori, Samira S.
- ORCID
- Venue
- Molecular Neurobiology
- Published
- 2017-02-06
- Volume
- 55
- Issue
- 2
- Pages
- 1430-1439
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2586054600
- Cited by
- 18
- References
- 5
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2019: 4
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- histone deacetylase inhibition, sodium butyrate, valproic acid, d-amphetamine, mania, bipolar disorder, cytokines, neuroinflammation, frontal cortex, striatum, interleukin-6, IL-10, IL-4, TNF-α, mood stabilizers
- MeSH terms
- Animals, Bipolar Disorder, Brain, Dextroamphetamine, Disease Models, Animal, Histone Deacetylases, Male, Motor Activity, Cytokines, Rats, Wistar, Antimanic Agents, Rats, Histone Deacetylase Inhibitors
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