Psychoactive properties of BNN27, a novel neurosteroid derivate, in male and female rats

Kokras, Nikolaos; Dioli, Chrysoula; Paravatou, Rafaella; Sotiropoulos, Marinos G; Delis, Foteini; Αντωνίου, Κατερίνα; Calogeropoulou, Theodora; Charalampopoulos, Ioannis; Gravanis, Achille; Dalla, Christina

doi:10.1007/s00213-020-05545-5

Cited by 13 publications

(16 citation statements)

References 78 publications

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“…The injection volume was 10mL/kg and the resulting DMSO exposure (35% v/v DMSO equaling 3.5 mL/kg) was low, and below the recommendation to not exceed 25% of the LD50, which has been found to be 14-20 mL/kg in mice [48]. As a result, no vehicle-related toxicity effects were observed, nor any animal suffering, in accordance with previous observations [49][50][51] and previous studies involving water-insoluble treatments [52][53][54]. The composition of the dissolved extracts, as prepared for animal treatment, was confirmed by HPLC-UV and LC-MS (Figure 1; Tables A1 and A2).…”

Section: Treatmentssupporting

confidence: 87%

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice

et al. 2020

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The aim of this study was to determine the cognitive and behavioral effects of extra virgin olive oil total phenolic content (TPC) and Sideritis (SID) extracts in female mice, and identify the associated neurochemical changes in the hippocampus and the prefrontal cortex. All animals received intraperitoneal low or high doses of TPC, SID or vehicle treatment for 7 days and were subjected to the Open Field (OF), Novel Object Recognition (NOR) and Tail Suspension Test (TST). The prefrontal cortex and hippocampus were dissected for analysis of neurotransmitters and aminoacids with high performance liquid chromatography with electrochemical detection (HPLC-ED). Both TPC doses enhanced vertical activity and center entries in the OF, which could indicate an anxiolytic-like effect. In addition, TPC enhanced non-spatial working memory and, in high doses, exerted antidepressant effects. On the other hand, high SID doses remarkably decreased the animals’ overall activity. Locomotor and exploratory activities were closely associated with cortical increases in serotonin turnover induced by both treatments. Cognitive performance was linked to glutamate level changes. Furthermore, TPC reduced cortical taurine levels, while SID reduced cortical aspartate levels. TPC seems to have promising cognitive, anxiolytic and antidepressant effects, whereas SID has sedative effects in high doses. Both extracts act in the brain, but their specific actions and properties merit further exploration.

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Section: Treatmentssupporting

confidence: 87%

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice

et al. 2020

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“…Consequently, considering the similarities between the BRB and the BBB, one could imply the penetration of the BBB by the molecule. The results of numerous in vivo experiments 2,8‐13 as well as in vitro assays 1,2,8,9 can support this allegation.…”

Section: Discussionmentioning

confidence: 94%

“…injections of a lower concentration of BNN27 with affirmative results as well. [8][9][10][11][12][13] as well as in vitro assays 1,2,8,9 can support this allegation.…”

Section: F I G U R Ementioning

confidence: 87%

“…The molecule seems to selectively bind to both NGF (Nerve Growth Factor) receptors, namely TrkA and p75 NTR neurotrophin receptors, 6,7 and thus demonstrate anti-inflammatory, neurotrophic, and anti-apoptotic activities in cell cultures 8,9 and animal models [8][9][10][11][12][13] for CNS (central nervous system) and retinal disease. 5,[14][15][16] Additionally, it is highly lipophilic with proven facility to cross artificial membranes that mimic the blood-brain barrier (BBB).…”

Section: Introductionmentioning

confidence: 99%

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Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration

Tsika

Tzatzarakis

Antimisiaris

et al. 2021

Pharmacology Res & Perspec

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BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57BL/6 mice and 48 Sprague–Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro‐orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography‐mass spectrometry (LC‐MS). Non‐compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant kel = 0.465 h−1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (Cmax) in the retina was detected at 2 h (tCtruemax) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC‐MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood–retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.

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“…Additional to its effect on neuronal cells, BNN27 induces TrkA phosphorylation of TrkA-expressing BV2 mouse glial cells in culture, decreasing the levels of interleukin (IL) 6 mRNA (Pediaditakis, Efstathopoulos, et al, 2016). BNN27 has shown beneficial and neuroprotective effects in animal models of amyotrophic lateral sclerosis (Glajch et al, 2016), retinal detachment (Tsoka et al, 2018), ketamineinduced psychosis (Zoupa et al, 2019), scopolamine-induced cognitive deficits (Pitsikas & Gravanis, 2017), and a model of retina degeneration in the streptozotocin-induced diabetic rats (Ibán-Arias et al, 2018), while recent studies also showed that this microneurotrophin is able to affect locomotion, progesterone, and testosterone levels, as well as the glutamatergic and GABAergic systems of the hippocampus and prefrontal cortex in a sexdependent way (Kokras et al, 2020). We have shown that BNN27, acting through the TrkA receptor, can exert a trophic action on OLs in vitro and in vivo in the cuprizone model of demyelination (Bonetto, et al 2017).…”

Section: Significancementioning

confidence: 99%

The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model

Kalafatakis

Patellis

Charalampopoulos

et al. 2021

J of Neuroscience Research

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Myelin, produced by oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS), is an evolutionary trait of vertebrates contributing to action potential propagation over long distances. Myelin disruption occurs in demyelinating diseases and results in the cell death of either OLs or Schwann cells, leading to axonal demyelination and degeneration causing impairments in motor and cognitive function. There is a variety of demyelinating diseases with different

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Psychoactive properties of BNN27, a novel neurosteroid derivate, in male and female rats

Cited by 13 publications

References 78 publications

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice

Quantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration

The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model

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