On an association between fear-induced aggression and striatal-enriched protein tyrosine phosphatase (STEP) in the brain of Norway rats

Moskaliuk, Vitalii; Kozhemyakina, R. V.; Базовкина, Д. В.; Terenina, Elena; Khomenko, T. M.; Волчо, К. П.; Салахутдинов, Н. Ф.; Куликов, А. В.; Науменко, В. С.; Kulikova, Elizabeth A.

doi:10.1016/j.biopha.2022.112667

Cited by 10 publications

(4 citation statements)

References 77 publications

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“…Our findings suggest that a higher expression of this receptor’s mRNA can also be associated with the absence of aggression in tame animals. Moreover, in a previous report, we noted that aggressive rats have higher anxiety than tame rats in the elevated plus maze test [ 41 ]. On the other hand, a knockout of the Htr1a gene also aggravates anxious behavior [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, in response to TC-2153 administration, aggressive rats showed a reduction in exon I expression in the hypothalamus and in the expressions of exons IV, V, and VII in the midbrain. Taking into account the results on the antiaggressive effect of TC-2153 obtained earlier [ 41 ], it is not surprising to see the main effects of this drug in the hypothalamus and midbrain because these brain structures are deeply involved in the regulation of aggressive behavior [ 68 ]. It is noteworthy that TC-2153 at the dose of 10 mg/kg elevated the expression of exon VI in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…Total RNA was extracted from the brain structures (cortex, hippocampus, hypothalamus, and midbrain) using the TRIzol Reagent (Ambion, Austin, TX, USA) according to a previously described procedure [ 41 ]. The extracted RNA was treated with RNase-free DNase (Promega, Fitchburg, WI, USA) and diluted to 0.125 µg/µL with diethyl pyrocarbonate-treated water.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, it was shown that the novel antidepressant benzopentathiepine TC-2153—when administered acutely or chronically—significantly diminishes the fear-induced aggression in aggressive rats and, after acute administration, has an anxiolytic effect on both tame and aggressive Norway rats [ 41 ]. TC-2153 is known to elevate the expression of the common protein-coding exon IX of the Bdnf gene [ 42 ] and to influence the serotonergic system in mice [ 43 , 44 , 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

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On Associations between Fear-Induced Aggression, Bdnf Transcripts, and Serotonin Receptors in the Brains of Norway Rats: An Influence of Antiaggressive Drug TC-2153

Moskaliuk

Kozhemyakina

Khomenko

et al. 2023

IJMS

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The Bdnf (brain-derived neurotrophic factor) gene contains eight regulatory exons (I–VIII) alternatively spliced to the protein-coding exon IX. Only exons I, II, IV, and VI are relatively well studied. The BDNF system and brain serotonergic system are tightly interconnected and associated with aggression. The benzopentathiepine TC-2153 affects both systems and exerts antiaggressive action. Our aim was to evaluate the effects of TC-2153 on the Bdnf exons I–IX’s expressions and serotonin receptors’ mRNA levels in the brain of rats featuring high aggression toward humans (aggressive) or its absence (tame). Aggressive and tame adult male rats were treated once with vehicle or 10 or 20 mg/kg of TC-2153. mRNA was quantified in the cortex, hippocampus, hypothalamus, and midbrain with real-time PCR. Selective breeding for high aggression or its absence affected the serotonin receptors’ and Bdnf exons’ transcripts differentially, depending on the genotype (strain) and brain region. TC-2153 had comprehensive effects on the Bdnf exons’ expressions. The main trend was downregulation in the hypothalamus and midbrain. TC-2153 increased 5-HT1B receptor hypothalamusc mRNA expression. For the first time, an influence of TC-2153 on the expressions of Bdnf regulatory exons and the 5-HT1B receptor was shown, as was an association between Bdnf regulatory exons and fear-induced aggression involving genetic predisposition.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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On Associations between Fear-Induced Aggression, Bdnf Transcripts, and Serotonin Receptors in the Brains of Norway Rats: An Influence of Antiaggressive Drug TC-2153

Moskaliuk

Kozhemyakina

Khomenko

et al. 2023

IJMS

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Pentathiepins are an understudied molecular prism of biological activities

Pozzetti,

Asquith

2024

Archiv der Pharmazie

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The pentathiepin core was first synthesized in 1971, and while synthetic techniques have progressed over subsequent decades, the biological applications of this heterocycle have received less attention and are only now becoming more apparent. The first natural product, varacin, was identified in 1991, showing cytotoxicity toward a human colon cancer cell line. More recently, the pentathiepin has acted as a surrogate to replace elemental sulfur, that was discovered as a hit in neurodegenerative animal models. A variety of other medicinal chemistry applications have recently been disclosed. Here, we summarize these indications and highlight the main synthetic pathways to access the pentathiepin core. We offer a concise summary and future perspective of this unique sulfur isosteric replacement.

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Uncovering the Significance of STEP61 in Alzheimer’s Disease: Structure, Substrates, and Interactome

et al. 2023

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On an association between fear-induced aggression and striatal-enriched protein tyrosine phosphatase (STEP) in the brain of Norway rats

Cited by 10 publications

References 77 publications

On Associations between Fear-Induced Aggression, Bdnf Transcripts, and Serotonin Receptors in the Brains of Norway Rats: An Influence of Antiaggressive Drug TC-2153

On Associations between Fear-Induced Aggression, Bdnf Transcripts, and Serotonin Receptors in the Brains of Norway Rats: An Influence of Antiaggressive Drug TC-2153

Pentathiepins are an understudied molecular prism of biological activities

Uncovering the Significance of STEP61 in Alzheimer’s Disease: Structure, Substrates, and Interactome

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