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Roy, T., Petersen, N. N., Gopalan, G., Gising, J., Hallberg, M. & Larhed, M. (2022). 2-Alkyl substituted benzimidazoles as a new class of selective AT2 receptor ligands. Bioorganic & Medicinal Chemistry, 66, Article ID 116804.
Open this publication in new window or tab >>2-Alkyl substituted benzimidazoles as a new class of selective AT2 receptor ligands
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2022 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 66, article id 116804Article in journal (Refereed) Published
Abstract [en]

Ligands comprising a benzimidazole rather than the imidazole ring that is common in AT2R ligands e.g. in the AT2R agonist C21, can provide both high affinity and receptor selectivity. In particular, compounds encompassing benzimidazoles, substituted in the 2-position with small bulky groups such as an isopropyl (Ki = 4.0 nM) or a tert-butyl (Ki = 5.3 nM) or alternatively a thiazole heterocycle (Ki = 5.1 nM) demonstrate high affinity and AT2R selectivity. An n-butyl chain, as found in the AT1R selective sartans, makes the ligand less receptor selective. The isobutyl group on the biaryl scaffold present in most AT2R selective ligands reported so far was originally derived from the nonselective potent AT1R/AT2R ligand L-162,313. Notably, in all ligands discussed herein, the isobutyl group was substituted by an n-propyl group and ligands with high affinity to AT2R were provided and in addition the majority of them demonstrate a favorable AT2R/AT1R selectivity. The introduction of fluoro atoms in various positions had no pronounced effect on the affinity data. Ligands with a thiazole or a tert-butyl group attached to the 2-position and with a terminal trifluoromethyl butoxycarbonyl sidechain exhibited a similar stability as C21 in human liver microsomes, while other ligands examined were less stable in the microsome assay.

Place, publisher, year, edition, pages
ElsevierElsevier, 2022
Keywords
Angiotensin II type 2 receptor, AT 2 R ligands, AT 2 R, AT 1 R selectivity, Benzimidazole sulfonyl carbamates, Liver microsomes
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-477515 (URN)10.1016/j.bmc.2022.116804 (DOI)000804934100008 ()35576659 (PubMedID)
Funder
Kjell and Marta Beijer FoundationThe Swedish Brain Foundation
Note

De två första författarna delar förstaförfattarskapet

Available from: 2022-06-21 Created: 2022-06-21 Last updated: 2024-01-15Bibliographically approved
Gopalan, G., Palo-Nieto, C., Petersen, N. N., Hallberg, M. & Larhed, M. (2022). Angiotensin II AT2 receptor ligands with phenylthiazole scaffolds. Bioorganic & Medicinal Chemistry, 65, Article ID 116790.
Open this publication in new window or tab >>Angiotensin II AT2 receptor ligands with phenylthiazole scaffolds
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2022 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 65, article id 116790Article in journal (Refereed) Published
Abstract [en]

The syntheses and the AT1R and AT2R binding data of a series of new small molecule ligands are reported. These ligands comprise a phenylthiazole scaffold rather than the biphenyl or phenylthiophene scaffolds found in essentially all of the previously described ligands originating from the nonselective AT1R/AT2R ligand L-162,313 and the AT2R selective agonist C21, the latter now in Phase II/III clinical trials. A phenylthiazole rather than the phenylthiophene scaffold that is present in the AT2R selective agonist C21 and in the AT2R selective antagonist C38 had a deleterious effect on the affinity to AT2R. Nevertheless, a significant improvement could be accomplished by introduction of a small bulky alkyl group in the 2-position of the imidazole ring attached through a methylene group bridge to the phenylthiazole scaffold. Hence, a combination of a 2-tert-butyl or a 2-isopropyl group and a butoxycarbonyl furnished potent AT2R selective ligands. Furthermore, a high affinity ligand derived from L-162,313 and exhibiting a > 35 fold selectivity for AT1R was identified (10). The ligand 21 with the 2-tert-butyl group and ~ 35 fold selectivity for AT2R, demonstrated high stability in human, rat and mouse liver microsomes and a very attractive profile with regard to the inhibition of common drug-metabolizing CYP enzymes. Thus, very low levels of inhibition of CYP 3A (5%), 2D6 (12%), 2C8 (26%), 2C9 (23%) and 2B6 (24%) were observed with the 2-tert-butyl derivative comprising the methoxycarbonyl sulfonamide function, levels that are significantly lower than those obtained with C21 under the same experimental conditions.

Place, publisher, year, edition, pages
ElsevierElsevier BV, 2022
Keywords
AT(1)R selectivity, Angiotensin II type 2 receptor, Phenylthiazole scaffolds, Liver microsomes, CYP enzyme inhibition, AT(2)R
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-476618 (URN)10.1016/j.bmc.2022.116790 (DOI)000802636800004 ()35550979 (PubMedID)
Funder
Kjell and Marta Beijer FoundationThe Swedish Brain Foundation
Available from: 2022-06-21 Created: 2022-06-21 Last updated: 2024-01-15Bibliographically approved
Stam, F., Lind, S. F., Schroff, A., Zelleroth, S., Nylander, E., Gising, J., . . . Hallberg, M. (2022). Hydrogen Peroxide Induced Toxicity Is Reversed by the Macrocyclic IRAP-Inhibitor HA08 in Primary Hippocampal Cell Cultures. Current Issues in Molecular Biology, 44(10), 5000-5012
Open this publication in new window or tab >>Hydrogen Peroxide Induced Toxicity Is Reversed by the Macrocyclic IRAP-Inhibitor HA08 in Primary Hippocampal Cell Cultures
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2022 (English)In: Current Issues in Molecular Biology, ISSN 1467-3037, E-ISSN 1467-3045, Vol. 44, no 10, p. 5000-5012Article in journal (Refereed) Published
Abstract [en]

Angiotensin IV (Ang IV), a metabolite of Angiotensin II, is a bioactive hexapeptide that inhibits the insulin-regulated aminopeptidase (IRAP). This transmembrane zinc metallopeptidase with many biological functions has in recent years emerged as a new pharmacological target. IRAP is expressed in a variety of tissues and can be found in high density in the hippocampus and neocortex, brain regions associated with cognition. Ang IV is known to improve memory tasks in experimental animals. One of the most potent IRAP inhibitors known today is the macrocyclic compound HA08 that is significantly more stable than the endogenous Ang IV. HA08 combines structural elements from Ang IV and the physiological substrates oxytocin and vasopressin, and binds to the catalytic site of IRAP. In the present study we evaluate whether HA08 can restore cell viability in rat primary cells submitted to hydrogen peroxide damage. After damaging the cells with hydrogen peroxide and subsequently treating them with HA08, the conceivable restoring effects of the IRAP inhibitor were assessed. The cellular viability was determined by measuring mitochondrial activity and lactate dehydrogenase (LDH) release. The mitochondrial activity was significantly higher in primary hippocampal cells, whereas the amount of LDH was unaffected. We conclude that the cell viability can be restored in this cell type by blocking IRAP with the potent macrocyclic inhibitor HA08, although the mechanism by which HA08 exerts its effects remains unclear.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
primary cell cultures, Angiotensin IV, insulin-regulated aminopeptidase (IRAP), hippocampus
National Category
Biochemistry and Molecular Biology Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-488237 (URN)10.3390/cimb44100340 (DOI)000874192000001 ()36286055 (PubMedID)
Available from: 2022-11-10 Created: 2022-11-10 Last updated: 2022-11-10Bibliographically approved
Zelleroth, S., Nylander, E., Kjellgren, E., Gröndbladh, A. & Hallberg, M. (2022). Nandrolone decanoate and testosterone undecanoate differently affect stress hormones, neurotransmitter systems, and general activity in the male rat. Behavioural Brain Research, 432, Article ID 113971.
Open this publication in new window or tab >>Nandrolone decanoate and testosterone undecanoate differently affect stress hormones, neurotransmitter systems, and general activity in the male rat
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2022 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 432, article id 113971Article in journal (Refereed) Published
Abstract [en]

Anabolic androgenic steroids (AAS) are frequently used to improve physical appearance and strength. AAS are known to affect muscle growth, but many AAS-users also experience psychiatric and behavioral changes after long-term use. The AAS-induced effects on the brain seem to depend on the type of steroid used, but the rationale behind the observed effect is still not clear. The present study investigated and compared the impact of nandrolone decanoate and testosterone undecanoate on body weight gain, levels of stress hormones, brain gene expression, and behavioral profiles in the male rat. The behavioral profile was determined using the multivariate concentric squared field test (MCSF-test). Blood plasma and brains were collected for further analysis using ELISA and qPCR. Nandrolone decanoate caused a reduction in body weight gain in comparison with both testosterone undecanoate and control. Rats receiving nandrolone decanoate also demonstrated decreased general activity in the MCSF. In addition, nandrolone decanoate reduced the plasma levels of ACTH in comparison with the control and increased the levels of corticosterone in comparison with testosterone undecanoate. The qPCR analysis revealed brain region-dependent changes in mRNA expression, where the hypothalamus was identified as the region most affected by the AAS. Alterations in neurotransmitter systems and stress hormones may contribute to the changes in behavior detected in the MCSF. In conclusion, both AAS affect the male rat, although, nandrolone decanoate has more pronounced impact on the physiological and the behavioral parameters measured.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Anabolic androgenic steroids, Brain gene expression, Multivariate concentric square field test, Nandrolone decanoate, Testosterone undecanoate, Wistar rat
National Category
Neurosciences
Research subject
Pharmaceutical Science
Identifiers
urn:nbn:se:uu:diva-480854 (URN)10.1016/j.bbr.2022.113971 (DOI)000860386000008 ()35738337 (PubMedID)
Funder
Kjell and Marta Beijer Foundation
Available from: 2022-07-21 Created: 2022-07-21 Last updated: 2022-10-14Bibliographically approved
Grönbladh, A., Nylander, E., Zelleroth, S. & Hallberg, M. (2021). Assessing Cell Viability Effects of Opioids in Primary Cortical Cells from Rat.. Methods in Molecular Biology, 2201, 171-180
Open this publication in new window or tab >>Assessing Cell Viability Effects of Opioids in Primary Cortical Cells from Rat.
2021 (English)In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 2201, p. 171-180Article in journal (Refereed) Published
Abstract [en]

Although the number of studies that have examined the impact of opioids on cell viability is very limited, it has clearly shown that opioids commonly used in the clinic can both decrease neurogenesis and induce cell death. These negative effects induced by opioids are worrying and there is a need for further in-depth investigations addressing the impact of opioids on cell function and cell viability. A useful in vitro approach for studying the effects of opioids on cellular function and viability is using primary cortical cell cultures obtained from embryonic day 17 (E17) rat embryos. These cell cultures contain both neurons and glial cells that provide a more physiologically relevant culture condition when compared to the use of various commercially available cell lines. The primary cortical cells can be cultivated in 96-well plates, treated with various concentrations of opioids, and cell viability functions such as mitochondrial function and membrane integrity can easily be assessed using specific colorimetric assays.

Place, publisher, year, edition, pages
Springer Nature, 2021
Keywords
Cell viability, Cortex, In vitro, LDH, MTT, Membrane integrity, Mitochondrial function, Primary cell culture, Rat
National Category
Pharmacology and Toxicology
Research subject
Pharmacology
Identifiers
urn:nbn:se:uu:diva-433557 (URN)10.1007/978-1-0716-0884-5_15 (DOI)32975798 (PubMedID)
Funder
Kjell and Marta Beijer Foundation
Available from: 2021-01-31 Created: 2021-01-31 Last updated: 2022-11-15Bibliographically approved
Bakalkin, G., Kahle, A., Sarkisyan, D., Watanabe, H., Lukoyanov, N., Carvalho, L. S., . . . Nosova, O. (2021). Coordinated expression of the renin-angiotensin genes in the lumbar spinal cord: Lateralization and effects of unilateral brain injury. European Journal of Neuroscience, 54(4), 5560-5573
Open this publication in new window or tab >>Coordinated expression of the renin-angiotensin genes in the lumbar spinal cord: Lateralization and effects of unilateral brain injury
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2021 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 54, no 4, p. 5560-5573Article in journal (Refereed) Published
Abstract [en]

In spite of its apparent symmetry, the spinal cord is asymmetric in its reflexes and gene expression patterns including leftward expression bias of the opioid and glutamate genes. To examine whether this is a general phenomenon for neurotransmitter and neurohormonal genes, we here characterized expression and co-expression (transcriptionally coordinated) patterns of genes of the renin-angiotensin system (RAS) that is involved in neuroprotection and pathological neuroplasticity in the left and right lumbar spinal cord. We also tested whether the RAS expression patterns were affected by unilateral brain injury (UBI) that rewired lumbar spinal neurocircuits. The left and right halves of the lumbar spinal cord were analysed in intact rats, and rats with left- or right-sided unilateral cortical injury, and left- or right-sided sham surgery. The findings were (i) lateralized expression of the RAS genes Ace, Agtr2 and Ren with higher levels on the left side; (ii) the asymmetry in coordination of the RAS gene expression that was stronger on the right side; (iii) the decay in coordination of co-expression of the RAS and neuroplasticity-related genes induced by the right-side but not left-side sham surgery and UBI; and (iv) the UBI-induced shift to negative regulatory interactions between RAS and neuroplasticity-related genes on the contralesional spinal side. Thus, the RAS genes may be a part of lateralized gene co-expression networks and have a role in a side-specific regulation of spinal neurocircuits.

Place, publisher, year, edition, pages
John Wiley & SonsWiley, 2021
Keywords
brain injury, co-expression patterns, gene expression, neuroplasticity, renin-angiotensin system, spinal cord
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-468861 (URN)10.1111/ejn.15360 (DOI)000674007100001 ()34145943 (PubMedID)
Funder
Swedish Research Council, K2014-62X12190-19-5Swedish Research Council, 2019-01771-3P.O. Zetterling Foundation
Available from: 2022-03-04 Created: 2022-03-04 Last updated: 2024-01-15Bibliographically approved
Nosova, O., Bazov, I., Karpyak, V., Hallberg, M. & Bakalkin, G. (2021). Epigenetic and Transcriptional Control of the Opioid Prodynorphine Gene: In-Depth Analysis in the Human Brain. Molecules, 26(11), Article ID 3458.
Open this publication in new window or tab >>Epigenetic and Transcriptional Control of the Opioid Prodynorphine Gene: In-Depth Analysis in the Human Brain
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2021 (English)In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 26, no 11, article id 3458Article, review/survey (Refereed) Published
Abstract [en]

Neuropeptides serve as neurohormones and local paracrine regulators that control neural networks regulating behavior, endocrine system and sensorimotor functions. Their expression is characterized by exceptionally restricted profiles. Circuit-specific and adaptive expression of neuropeptide genes may be defined by transcriptional and epigenetic mechanisms controlled by cell type and subtype sequence-specific transcription factors, insulators and silencers. The opioid peptide dynorphins play a critical role in neurological and psychiatric disorders, pain processing and stress, while their mutations cause profound neurodegeneration in the human brain. In this review, we focus on the prodynorphin gene as a model for the in-depth epigenetic and transcriptional analysis of expression of the neuropeptide genes. Prodynorphin studies may provide a framework for analysis of mechanisms relevant for regulation of neuropeptide genes in normal and pathological human brain.

Place, publisher, year, edition, pages
MDPIMDPI AG, 2021
Keywords
prodynorphin, epigenetics, transcription, human brain
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-447678 (URN)10.3390/molecules26113458 (DOI)000660409300001 ()
Funder
Swedish Research Council, K2014-62X12190-19-5Swedish Research Council, 2019-01771-3
Available from: 2021-06-29 Created: 2021-06-29 Last updated: 2024-01-15Bibliographically approved
Watanabe, H., Kononenko, O., Sarkisyan, D., Andersen, M. S., Carvalho, L., Galatenko, V., . . . Bakalkin, G. (2021). Left-right side-specific neuropeptide mechanism mediates contralateral responses to a unilateral brain injury. eNeuro, 8(3), Article ID 0548-20.2021.
Open this publication in new window or tab >>Left-right side-specific neuropeptide mechanism mediates contralateral responses to a unilateral brain injury
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2021 (English)In: eNeuro, E-ISSN 2373-2822, Vol. 8, no 3, article id 0548-20.2021Article in journal (Refereed) Published
Abstract [en]

Neuropeptides are implicated in control of lateralized processes in the brain. A unilateral brain injury (UBI) causes the contra- and ipsilesional side-specific postural and sensorimotor deficits. To examine whether opioid neuropeptides mediate UBI induced asymmetric processes we compared effects of opioid antagonists on the contra- and ipsilesional hindlimb responses to the left- and right-sided injury in rats. UBI induced hindlimb postural asymmetry (HL-PA) with the contralesional hindlimb flexion, and activated contralesional withdrawal reflex of extensor digitorum longus (EDL) evoked by electrical stimulation and recorded with EMG technique. No effects on the interossei (Int) and peroneaus longus (PL) were evident. The general opioid antagonist naloxone blocked postural effects, did not change EDL asymmetry while uncovered cryptic asymmetry in the PL and Int reflexes induced by UBI. Thus the spinal opioid system may either mediate or counteract the injury effects. Strikingly, effects of selective opioid antagonists were the injury side-specific. The mu- and kappa-antagonists beta-funaltrexamine and nor-binaltorphimine, respectively, reduced postural asymmetry after the right but not left UBI. In contrast, the delta-antagonist naltrindole inhibited HL-PA after the left but not right side brain injury. The opioid gene expression and opioid peptides were lateralized in the lumbar spinal cord, and coordination between expression of the opioid and neuroplasticity-related genes was impaired by UBI that together may underlie the side-specific effects of the antagonists. We suggest that mirror-symmetric neural circuits that mediate effects of left and right brain injury on the contralesional hindlimbs are differentially controlled by the lateralized opioid system. Significance statement Functional specialization of the left and right hemispheres is an organizing principle of the brain. Lasting regulation of lateralized processes may be accomplished by paracrine neurohormonal mechanisms that preferentially operate in the left or right hemisphere. Our findings support this hypothesis by demonstration that mirror-symmetric neural circuits that control the left and right hindlimbs may be regulated by the left- and right-side specific neuropeptide mechanisms. Neuropeptides may differentially target the left and right counterparts of these circuits, and in this way control the left-right balance in their functional performance. This bipartite mechanism may be based on lateralization of the neuropeptide systems, and may operate in the spinal cord or control neural pathways descending from the brain to contralateral motoneurons.

Place, publisher, year, edition, pages
Society for Neuroscience, 2021
Keywords
brain injury, postural asymmetry, withdrawal reflexes, opioid system, left-right side specific regulation
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-461148 (URN)10.1523/ENEURO.0548-20.2021 (DOI)000719055700003 ()33903183 (PubMedID)
Funder
Swedish Research Council, K2014-62X-12190-19-5Swedish Research Council, 2019-01771-3Swedish Research Council, 2016-06195Lars Hierta Memorial FoundationP.O. Zetterling FoundationRegion Skåne, F2018/1490
Available from: 2021-12-13 Created: 2021-12-13 Last updated: 2021-12-13Bibliographically approved
Wannberg, J., Gising, J., Lindman, J., Salander, J., Gutiérrez-de-Terán, H., Ablahad, H., . . . Larhed, M. (2021). N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands. Bioorganic & Medicinal Chemistry, 29, Article ID 115859.
Open this publication in new window or tab >>N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands
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2021 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 29, article id 115859Article in journal (Refereed) Published
Abstract [en]

A series of meta-substituted acetophenone derivatives, encompassing N-(alkyloxycarbonyl)thiophene sulfonamide fragments have been synthesized. Several selective AT2 receptor ligands were identified, among those a tert-butylimidazole derivative (20) with a Ki of 9.3 nM, that demonstrates a high stability in human liver microsomes (t½ = 62 min) and in human hepatocytes (t½ = 194 min). This methyloxycarbonylthiophene sulfonamide is a 20-fold more potent binder to the AT2 receptor and is considerably more stable in human liver microsomes, than a previously reported and broadly studied structurally related AT2R prototype antagonist 3 (C38). Ligand 20 acts as an AT2R agonist and caused an AT2R mediated concentration-dependent vasorelaxation of pre-contracted mouse aorta. Furthermore, in contrast to imidazole derivative C38, the tert-butylimidazole derivative 20 is a poor inhibitor of CYP3A4, CYP2D6 and CYP2C9. It is demonstrated herein that smaller alkyloxycarbonyl groups make the ligands in this series of AT2R selective compounds less prone to degradation and that a high AT2 receptor affinity can be retained after truncation of the alkyloxycarbonyl group. Binding modes of the most potent AT2R ligands were explored by docking calculations combined with molecular dynamics simulations.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
AT2R ligands, Angiotensin II type 2 receptor, Carboxylic acid bioisosteres, Liver microsomes, Sulfonyl carbamates
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-433559 (URN)10.1016/j.bmc.2020.115859 (DOI)000612172300003 ()33309749 (PubMedID)
Funder
Kjell and Marta Beijer FoundationThe Swedish Brain FoundationScience for Life Laboratory, SciLifeLabSwedish National Infrastructure for Computing (SNIC)
Available from: 2021-01-31 Created: 2021-01-31 Last updated: 2024-01-15Bibliographically approved
Zelleroth, S., Nylander, E., Örtenblad, A., Stam, F., Nyberg, F., Grönbladh, A. & Hallberg, M. (2021). Structurally different anabolic androgenic steroids reduce neurite outgrowth and neuronal viability in primary rat cortical cell cultures. Journal of Steroid Biochemistry and Molecular Biology, 210, Article ID 105863.
Open this publication in new window or tab >>Structurally different anabolic androgenic steroids reduce neurite outgrowth and neuronal viability in primary rat cortical cell cultures
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2021 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 210, article id 105863Article in journal (Refereed) Published
Abstract [en]

The illicit use of anabolic androgenic steroids (AAS) among adolescents and young adults is a major concern due to the unknown and unpredictable impact of AAS on the developing brain and the consequences of this on mental health, cognitive function and behaviour. The present study aimed to investigate the effects of supra-physiological doses of four structurally different AAS (testosterone, nandrolone, stanozolol and trenbolone) on neurite development and cell viability using an in vitro model of immature primary rat cortical cell cultures. A high-throughput screening image-based approach, measuring the neurite length and number of neurons, was used for the analysis of neurite outgrowth. In addition, cell viability and expression of the Tubb3 gene (encoding the protein beta-III tubulin) were investigated. Testosterone, nandrolone, and trenbolone elicited adverse effects on neurite outgrowth as deduced from an observed reduced neurite length per neuron. Trenbolone was the only AAS that reduced the cell viability as indicated by a decreased number of neurons and declined mitochondrial function. Moreover, trenbolone downregulated the Tubb3 mRNA expression. The adverse impact on neurite development was neither inhibited nor supressed by the selective androgen receptor (AR) antagonist, flutamide, suggesting that the observed effects result from another mechanism or mechanisms of action that are operating apart from AR activation. The results demonstrate a possible AAS-induced detrimental effect on neuronal development and regenerative functions. An impact on these events, that are essential mechanisms for maintaining normal brain function, could possibly contribute to behavioural alterations seen in AAS users.

Keywords
Anabolic androgenic steroids, Neurite outgrowth, Neurotoxicity, Primary cortical cell culture, Rat
National Category
Basic Medicine Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-439046 (URN)10.1016/j.jsbmb.2021.105863 (DOI)000652020500001 ()33677017 (PubMedID)
Funder
Kjell and Marta Beijer FoundationThe Swedish Brain FoundationSwedish Research Council, 9459
Available from: 2021-03-29 Created: 2021-03-29 Last updated: 2022-08-03Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9835-870x

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