| 1. |
- Studer, Erik, et al.
(författare)
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Serotonin Depletion-Induced Maladaptive Aggression Requires the Presence of Androgens
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- The sex hormone testosterone and the neurotransmitter serotonin exert opposite effects on several aspects of behavior including territorial aggression. It is however not settled if testosterone exerts its pro-aggressive effects by reducing serotonin transmission and/or if the anti-aggressive effect of serotonin requires the presence of the androgen. Using the resident intruder test, we now show that administration of the serotonin synthesis inhibitor parachlorophenylalanine (300 mg/kg x 3 days) increases the total time of attack as well as the percentage amount of social behavior spent on attack but not that spent on threat - i.e. that it induces a pattern of unrestricted, maladaptive aggression - in gonadectomized C57Bl/6 male mice receiving testosterone replacement; in contrast, it failed to reinstate aggression in those not given testosterone. Whereas these results suggest the pro-aggressive effect of testosterone to be independent of serotonin, and not caused by an inhibition of serotonergic activity, the pCPA-induced induction of maladaptive aggression appears to require the presence of the hormone. In line with these findings, pCPA enhanced the total time of attack as well the relative time spent on attacks but not threats also in wild-type gonadally intact male C57Bl/6 mice, but failed to reinstate aggression in mice rendered hypo-aggressive by early knock-out of androgen receptors in the brain (AR(NesDel) mice). We conclude that androgenic deficiency does not dampen aggression by unleashing an anti-aggressive serotonergic influence; instead serotonin seems to modulate aggressive behavior by exerting a parallel-coupled inhibitory role on androgen-driven aggression, which is irrelevant in the absence of the hormone, and the arresting of which leads to enhanced maladaptive aggression.
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| 2. |
- Becirovic, Ema, 1992-
(författare)
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Signal Processing Aspects of Massive MIMO
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Massive MIMO (multiple-input-multiple-output) is a technology that uses an antenna array with a massive number of antennas at the wireless base station. It has shown widespread benefit and has become an inescapable solution for the future of wireless communication. The mainstream literature focuses on cases when high data rates for a handful of devices are of priority. In reality, due to the diversity of applications, no solution is one-size-fits-all. This thesis provides signal-processing solutions for three challenging situations. The first challenging situation deals with the acquisition of channel estimates when the signal-to-noise-ratio (SNR) is low. The benefits of massive MIMO are unlocked by having good channel estimates. By the virtue of reciprocity in time-division duplex, the estimates are obtained by transmitting pilots on the uplink. However, if the uplink SNR is low, the quality of the channel estimates will suffer and consequently the spectral efficiency will also suffer. This thesis studies two cases where the channel estimates can be improved: one where the device is stationary such that the channel is constant over many coherence blocks and one where the device has access to accurate channel estimates such that it can design its pilots based on the knowledge of the channel. The thesis provides algorithms and methods that exploit the aforementioned structures which improve the spectral efficiency. Next, the thesis considers massive machine-type communications, where a large number of simple devices, such as sensors, are communicating with the base station. This thesis provides a quantitative study on which type of benefits massive MIMO can provide for this communication scenario — many devices can be spatially multiplexed and their battery life can be increased. Further, activity detection is also studied and it is shown that the channel hardening and favorable propagation properties of massive MIMO can be exploited to design efficient detection algorithms. The third part of the thesis studies a more specific application of massive MIMO, namely federated learning. In federated learning, the goal is for the devices to collectively train a machine learning model based on their local data by only transmitting model updates to the base station. Sum channel estimation has been advocated for blind over-the-air federated learning since fewer communication resources are required to obtain such estimates. On the contrary, this thesis shows that individually estimating each device's channel can save a huge number of resources owing to the fact that it allows for individual processing such as gradient sparsification which in turn saves a huge number of resources that compensates for the channel estimation overhead.
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| 3. |
- Egecioglu, Emil, 1977, et al.
(författare)
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The role of ghrelin signalling for sexual behaviour in male mice.
- 2016
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Ingår i: Addiction biology. - : Wiley. - 1369-1600 .- 1355-6215. ; 21:2, s. 348-59
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin, a gut-brain signal, is well known to regulate energy homeostasis, food intake and appetite foremost via hypothalamic ghrelin receptors (GHS-R1A). In addition, ghrelin activates the reward systems in the brain, namely the mesolimbic dopamine system, and regulates thereby the rewarding properties of addictive drugs as well as of palatable foods. Given that the mesolimbic dopamine system mandates the reinforcing properties of addictive drugs and natural rewards, such as sexual behaviour, we hypothesize that ghrelin plays an important role for male sexual behaviour, a subject for the present studies. Herein we show that ghrelin treatment increases, whereas pharmacological suppression (using the GHSR-1A antagonist JMV2959) or genetic deletion of the GHS-R1A in male mice decreases the sexual motivation for as well as sexual behaviour with female mice in oestrus. Pre-treatment with L-dopa (a dopamine precursor) prior to treatment with JMV2959 significantly increased the preference for female mouse compared with vehicle treatment. On the contrary, treatment with 5-hydroxythyptohan (a precursor for serotonin) prior to treatment with JMV2959 decreased the sexual motivation compared to vehicle. In separate experiments, we show that ghrelin and GHS-R1A antagonism do not affect the time spent over female bedding as measured in the androgen-dependent bedding test. Collectively, these data show that the hunger hormone ghrelin and its receptor are required for normal sexual behaviour in male mice and that the effects of the ghrelin signalling system on sexual behaviour involve dopamine neurotransmission.
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| 4. |
- Engdahl, Cecilia, 1983, et al.
(författare)
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Role of Androgen and Estrogen Receptors for the Action of Dehydroepiandrosterone (DHEA)
- 2014
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 155:3, s. 889-896
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Tidskriftsartikel (refereegranskat)abstract
- Dehydroepiandrosterone (DHEA) is an abundant steroid hormone, and its mechanism of action is yet to be determined. The aim of this study was to elucidate the importance of androgen receptors (ARs) and estrogen receptors (ERs) for DHEA function. Orchidectomized C57BL/6 mice were treated with DHEA, DHT, 17 beta-estradiol-3-benzoate (E2), or vehicle. Orchidectomized AR-deficient (ARKO) mice and wild-type (WT) littermates were treated with DHEA or vehicle for 2.5 weeks. At termination, bone mineral density (BMD) was evaluated, thymus and seminal vesicles were weighted, and submandibular glands (SMGs) were histologically examined. To evaluate the in vivo ER activation of the classical estrogen signaling pathway, estrogen response element reporter mice were treated with DHEA, DHT, E2, or vehicle, and a reporter gene was investigated in different sex steroid-sensitive organs after 24 hours. DHEA treatment increased trabecular BMD and thymic atrophy in both WT and ARKO mice. In WT mice, DHEA induced enlargement of glands in the SMGs, whereas this effect was absent in ARKO mice. Furthermore, DHEA was able to induce activation of classical estrogen signaling in bone, thymus, and seminal vesicles but not in the SMGs. In summary, the DHEA effects on trabecular BMD and thymus do not require signaling via AR and DHEA can activate the classical estrogen signaling in these organs. In contrast, DHEA induction of gland size in the SMGs is dependent on AR and does not involve classical estrogen signaling. Thus, both ERs and ARs are involved in mediating the effects of DHEA in an organ-dependent manner.
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| 5. |
- Karlsson, Sara, 1980, et al.
(författare)
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Neural Androgen Receptors Modulate Gene Expression and Social Recognition But Not Social Investigation
- 2016
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The role of sex and androgen receptors (ARs) for social preference and social memory is rather unknown. In this study of mice we compared males, females and males lacking ARs specifically in the nervous system, ARNesDel, with respect to social preference, assessed with the three-chambered apparatus test, and social recognition, assessed with the social discrimination procedure. In the social discrimination test we also evaluated the tentative importance of the sex of the stimulus animal. Novel object recognition and olfaction were investigated to complement the results from the social tests. Gene expression analysis was performed to reveal molecules involved in the effects of sex and androgens on social behaviors. All three test groups showed social preference in the three-chambered apparatus test. In both social tests an AR independent sexual dimorphism was seen in the persistence of social investigation of female conspecifics, whereas the social interest toward male stimuli mice was similar in all groups. Male and female controls recognized conspecifics independent of their sex, whereas ARNesDel males recognized female but not male stimuli mice. Moreover, the non-social behaviors were not affected by AR deficiency. The gene expression analyses of hypothalamus and amygdala indicated that Oxtr, Cd38, Esrl, Cyp19a1, Ucn3, Crh. and Gtf2i were differentially expressed between the three groups. In conclusion, our results suggest that ARs are required for recognition of male but not female conspecifics, while being dispensable for social investigation toward both sexes. In addition, the AR seems to regulate genes related to oxytocin, estrogen and William's syndrome.
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| 6. |
- Leimbach, David, 1992, et al.
(författare)
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The electron affinity of astatine
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- One of the most important properties influencing the chemical behavior of an element is the electron affinity (EA). Among the remaining elements with unknown EA is astatine, where one of its isotopes, 211At, is remarkably well suited for targeted radionuclide therapy of cancer. With the At− anion being involved in many aspects of current astatine labeling protocols, the knowledge of the electron affinity of this element is of prime importance. Here we report the measured value of the EA of astatine to be 2.41578(7) eV. This result is compared to state-of-the-art relativistic quantum mechanical calculations that incorporate both the Breit and the quantum electrodynamics (QED) corrections and the electron–electron correlation effects on the highest level that can be currently achieved for many-electron systems. The developed technique of laser-photodetachment spectroscopy of radioisotopes opens the path for future EA measurements of other radioelements such as polonium, and eventually super-heavy elements.
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| 7. |
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| 8. |
- Näslund, Jakob, et al.
(författare)
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Differences in anxiety-like behavior within a batch of wistar rats are associated with differences in serotonergic transmission, enhanced by acute sri administration, and abolished by serotonin depletion
- 2015
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press (OUP). - 1461-1457 .- 1469-5111. ; 18:8, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The anxiety-reducing effect of long-term administration of serotonin reuptake inhibitors is usually seen only in subjects with anxiety disorders, and such patients are also abnormally inclined to experience a paradoxical anxietyenhancing effect of acute serotonin reuptake inhibition. These unique responses to serotonin reuptake inhibitors in anxietyprone subjects suggest, as do genetic association studies, that inter-individual differences in anxiety may be associated with differences in serotonergic transmission. Methods: The one-third of the animals within a batch of Wistar rats most inclined to spend time on open arms in the elevated plus maze were compared with the one-third most inclined to avoid them with respect to indices of brain serotonergic transmission and how their behavior was influenced by serotonin-modulating drugs. Results: "Anxious" rats displayed higher expression of the tryptophan hydroxylase-2 gene and higher levels of the tryptophan hydroxylase-2 protein in raphe and also higher levels of serotonin in amygdala. Supporting these differences to be important for the behavioral differences, serotonin depletion obtained by the tryptophan hydroxylase-2 inhibitor p-chlorophenylalanine eliminated them by reducing anxiety in "anxious" but not "non-anxious" rats. Acute administration of a serotonin reuptake inhibitor, paroxetine, exerted an anxiety-enhancing effect in "anxious" but not "non-anxious" rats, which was eliminated by long-term pretreatment with another serotonin reuptake inhibitor, escitalopram. Conclusions: Differences in an anxiogenic impact of serotonin, which is enhanced by acute serotonin reuptake inhibitor administration, may contribute to differences in anxiety-like behavior amongst Wistar rats..
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| 9. |
- Näslund, Jakob, et al.
(författare)
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Effects of gonadectomy and serotonin depletion on inter-individual differences in anxiety-like behaviour in male Wistar rats
- 2016
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 308, s. 160-165
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies in Wistar rats suggest inter-individual differences in anxiety-like behaviour as assessed using the elevated plus maze (EPM), both between sexes and among males, to be abolished by serotonin depletion. To shed further light on the influence of sex steroids and serotonin - and on the interplay between the two - on proneness for EPM-assessed anxiety in males, outbred Wistar rats were divided into those with high and low anxiety, respectively, and exposed to gonadectomy or sham operation followed by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine, or saline. Whereas gonadectomy enhanced anxiety-like behaviour in low anxiety rats so that these no longer differed in this regard from the high anxiety group, serotonin depletion reversed this effect, and also reduced anxiety in the low anxiety group regardless of gonadal state. A previously observed association between high anxiety-like behaviour and high expression of the serotonin-synthesizing enzyme tryptophan hydroxylase 2 (Tph2) in the raphe was confirmed in sham-operated animals but absent in gonadectomised rats, an ANCOVA revealing a significant interactive effect of baseline anxiety and gonadal state on Tph2 expression. It is suggested that androgens may contribute to upholding inter-individual differences in anxiety-like behaviour in male rats by interacting with serotonergic neurotransmission. (C) 2016 The Authors. Published by Elsevier B.V.
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| 10. |
- Näslund, Jakob, et al.
(författare)
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Expression of 22 serotonin-related genes in rat brain after sub-acute serotonin depletion or reuptake inhibition
- 2020
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 32:3, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Although the assessment of expression of serotonin-related genes in experimental animals has become a common strategy to shed light on variations in brain serotonergic function, it remains largely unknown to what extent the manipulation of serotonin levels causes detectable changes in gene expression. We therefore chose to investigate how sub-acute depletion or elevation of brain serotonin influences the expression of a number of serotonin-related genes in six brain areas. Methods: Male Wistar rats were administered a serotonin synthesis inhibitor, para-chlorophenylalanine (p-CPA), or a serotonin reuptake inhibitor, paroxetine, for 3 days and then sacrificed. The expression of a number of serotonin-related genes in the raphe nuclei, hypothalamus, amygdala, striatum, hippocampus and prefrontal cortex was investigated using real-time quantitative PCR (rt-qPCR). Results: While most of the studied genes were uninfluenced by paroxetine treatment, we could observe a robust downregulation of tryptophan hydroxylase-2 in the brain region where the serotonergic cell bodies reside, that is, the raphe nuclei. p-CPA induced a significant increase in the expression of Htr1b and Htr2a in amygdala and of Htr2c in the striatum and a marked reduction in the expression of Htr6 in prefrontal cortex; it also enhanced the expression of the brain-derived neurotrophic factor (Bdnf) in raphe and hippocampus. Conclusion: With some notable exceptions, the expression of most of the studied genes is left unchanged by short-term modulation of extracellular levels of serotonin.
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| 11. |
- Näslund, Jakob, et al.
(författare)
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Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat.
- 2013
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 1432-2072 .- 0033-3158. ; 230:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Numerous studies suggest (1) that a major physiological role of brain serotonin-containing neurons is to modulate sex steroid-driven behaviour such as sex and aggression, (2) that sex steroids influence brain serotonergic neurotransmission and (3) that brain serotonergic neurotransmission displays sexual dimorphism. Such observations indicate that an important task for brain serotonin is to either enhance or counteract sex differences in behaviour. METHODS: To test this hypothesis, we explored the effect of short-term serotonin depletion on the behaviour of adult male and female rats in a behavioural paradigm in which males and females have been shown to behave differently, i.e. the elevated plus maze. RESULTS: Two rounds of testing of untreated Wistar rats confirmed the previous observation that females make more entries into open arms (round 1, p=0.001; round 2, p=0.008) and spend more time on these arms (round 1, p≤0.001; round 2, p=0.006) than males; in addition, males displayed fewer entries into closed arms upon habituation, i.e. at the second round (p≤0.001) than did females. Administration of the tryptophan hydroxylase inhibitor para-chloro-phenylalanine, at a regimen (300mg/kg/day for 3days), markedly reducing brain content of serotonin, enhanced entries upon open arms (p=0.01) and time spent on open arms (p=0.004) in males but exerted no such effects in females (p=0.9 and p=0.9, respectively); moreover, it reduced entries into closed arms in females (p≤0.001) but not in males (p=0.1). CONCLUSIONS: Serotonin depletion abolishing the sex differences observed at baseline supports the theory that serotonin aids to uphold certain sex differences in behaviour.
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| 12. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Estrogen receptor-α expression in neuronal cells affects bone mass.
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:3, s. 983-988
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Tidskriftsartikel (refereegranskat)abstract
- It has generally been assumed that bone mass is controlled by endocrine mechanisms and the local bone environment. Recent findings demonstrate that central pathways are involved in the regulation of bone mass. Estrogen is involved in the regulation of bone homeostasis and the CNS is also a target for estrogen actions. The aim of this study was to investigate in vivo the role of central estrogen receptor-α (ERα) expression for bone mass. Nestin-Cre mice were crossed with ERα(flox) mice to generate mice lacking ERα expression specifically in nervous tissue (nestin-ERα(-/-)). Bone mineral density was increased in both the trabecular and cortical bone compartments in nestin-ERα(-/-) mice compared with controls. Femoral bone strength was increased in nestin-ERα(-/-) mice, as demonstrated by increased stiffness and maximal load of failure. The high bone mass phenotype in nestin-ERα(-/-) mice was mainly caused by increased bone formation. Serum leptin levels were elevated as a result of increased leptin expression in white adipose tissue (WAT) and slightly increased amount of WAT in nestin-ERα(-/-) mice. Leptin receptor mRNA levels were reduced in the hypothalamus but not in bone. In conclusion, inactivation of central ERα signaling results in increased bone mass, demonstrating that the balance between peripheral stimulatory and central inhibitory ERα actions is important for the regulation of bone mass. We propose that the increased bone mass in nestin-ERα(-/-) mice is mediated via decreased central leptin sensitivity and thereby increased secretion of leptin from WAT, which, in turn, results in increased peripheral leptin-induced bone formation.
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| 13. |
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| 14. |
- Studer, Christoph, et al.
(författare)
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PAR-Aware Large-Scale Multi-User MIMO-OFDM Downlink
- 2013
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Ingår i: IEEE Journal on Selected Areas in Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0733-8716 .- 1558-0008. ; 31:2, s. 303-313
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Tidskriftsartikel (refereegranskat)abstract
- We investigate an orthogonal frequency-division multiplexing (OFDM)-based downlink transmission scheme for large-scale multi-user (MU) multiple-input multiple-output (MIMO) wireless systems. The use of OFDM causes a high peak-to-average (power) ratio (PAR), which necessitates expensive and power-inefficient radio-frequency (RF) components at the base station. In this paper, we present a novel downlink transmission scheme, which exploits the massive degrees-of-freedom available in large-scale MU-MIMO-OFDM systems to achieve low PAR. Specifically, we propose to jointly perform MU precoding, OFDM modulation, and PAR reduction by solving a convex optimization problem. We develop a corresponding fast iterative truncation algorithm (FITRA) and show numerical results to demonstrate tremendous PAR-reduction capabilities. The significantly reduced linearity requirements eventually enable the use of low-cost RF components for the large-scale MU-MIMO-OFDM downlink.
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| 15. |
- Studer, Christoph, et al.
(författare)
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PAR-aware multi-user precoder for the large-scale MIMO-OFDM downlink
- 2012
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Konferensbidrag (refereegranskat)abstract
- We consider an orthogonal frequency-division multiplexing (OFDM)-based downlink transmission scheme for large-scale multi-user (MU) multiple-input multiple-output (MIMO) wireless systems. In order to transmit signals with low peak-to-average (power) ratio (PAR), we propose to exploit the massive degrees-of-freedom available in large-scale MU-MIMO-OFDM systems. Specifically, we jointly perform MU precoding, OFDM modulation, and PAR reduction by solving a convex optimization problem at the base station. Numerical results demonstrate tremendous PAR-reduction capabilities of the proposed method, which eventually enables us to use low-cost RF components for the large-scale MU-MIMO-OFDM downlink.
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| 16. |
- Studer, Erik, et al.
(författare)
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Significance and Interrelationship of the Symptoms Listed in the DSM Criteria for Premenstrual Dysphoric Disorder.
- 2023
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Ingår i: Psychiatric research and clinical practice. - 2575-5609. ; 5:3, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- While premenstrual dysphoric disorder (PMDD) as defined in DSM has become an established diagnosis, and a formal indication for drug treatment, the relative impact of the disparate symptoms named in the criteria, and to what extent they indeed constitute parts of one syndrome, remains insufficiently clarified. We have therefore explored the frequency, impact, and inter-relationship of different PMDD symptoms.Using a web survey, 10,457 Swedish women of fertile age were asked to retrospectively assess if they experience reduced functioning due to symptoms clearly associated with the premenstrual phase. Those responding affirmatively reported presence, severity, and impact of each symptom named in the PMDD criteria.Nine percent reported impairing premenstrual symptoms. Whereas irritability was reported to cause impairment in 77% of those passing the gate questions, somatic symptoms were common but seldom causing impairment. A vast majority reported presence of at least 5 different symptoms, as required to meet the PMDD criteria, but few reported each of 5 different symptoms to be severe or impairing. An analysis of the association between symptoms revealed clear-cut clustering of somatic and mood symptoms, respectively.While retrospective account suggested irritability to be the clinically most important premenstrual symptom, some of the complaints named in the PMDD criteria were not or only weakly associated with mood symptoms and also reported to be of limited clinical significance. It is concluded that regarding all symptoms listed in the DSM criteria as clinically relevant manifestations of one and the same syndrome may be questioned.
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| 17. |
- Studer, Erik, et al.
(författare)
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The effects of the dopamine stabilizer (-)-OSU6162 on aggressive and sexual behavior in rodents
- 2016
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine stabilizer (-)-OSU61612 dampens locomotion in rodents rendered hyperactive by exposure to a novel environment or treatment with amphetamine, but stimulates locomotion in habituated animals displaying low motor activity, tentatively exerting this profile by selectively blocking extrasynaptic D2 receptors. The major aim of the present study was to explore the possible usefulness of (-)-OSU61612 as an anti-aggressive drug. To this end, the effect of (-)-OSU61612 on isolation-induced aggression in male mice and estrous cycle-dependent aggression in female rats were studied using the resident intruder test; in addition, the possible influence of (-)-OSU61612 on sexual behavior in male mice and on elevated plus maze (EPM) performance in male rats were assessed. (-)-OSU61612 at doses influencing neither locomotion nor sexual activity reduced aggression in male mice. The effect was observed also in serotonin-depleted animals and is hence probably not caused by the antagonism of serotonin receptors displayed by the drug; refuting the possibility that it is due to 5-HT1B activation, it was also not counteracted by isamoltane. (-)-OSU61612 did not display the profile of an anxiogenic or anxiolytic drug in the EPM but caused a general reduction in activity that is well in line with the previous finding that it reduces exploratory behavior of non-habituated animals. In line with the observations in males, (-)-OSU61612 reduced estrus cycle-related aggression in female Wistar rats, a tentative animal model of premenstrual dysphoria. By stabilizing dopaminergic transmission, (-)-OSU61612 may prove useful as a well-tolerated treatment of various forms of aggression and irritability.
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| 18. |
- Vestlund, Jesper, et al.
(författare)
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Ghrelin and aggressive behaviours—Evidence from preclinical and human genetic studies
- 2019
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 104, s. 80-88
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Aggressive behaviour is of crucial importance in the defence for limited resources including food and mates and involves central serotonin as well as dopamine signalling. As ghrelin modulates food intake and sexual behaviour we initially investigated the hypothesis that central ghrelin signalling regulates aggressive behaviour in the resident intruder paradigm in male mice. Moreover, interaction between ghrelin signalling and serotonergic, noradrenergic as well as dopaminergic neurotransmission in aggression was investigated. The relevance of ghrelin for human aggression per se as well as for aggression induced by alcohol was evaluated in a human genetic association study comprising young men (n = 784) from the normal population assessed for anti-social behaviours. The present study demonstrates that central ghrelin infusion, but not ghrelin administered systemically, increases aggression. Moreover aggressive behaviour is decreased by pharmacological suppression of the growth hormone secretagogue receptor-1 A (GHSR-1A) by JMV2959. As indicated by the ex vivo biochemical data serotonin, rather than dopamine or noradrenaline, in amygdala may have central roles for the ability of JMV2959 to reduce aggression. This link between central serotonin, GHSR-1A and aggression is further substantiated by the behavioural data showing that JMV2959 cannot decrease aggression following depletion of central serotonin signalling. The genetic association study demonstrates that males carrying the Leu72Leu genotype of the pre-pro-ghrelin gene and displaying hazardous alcohol use are more aggressive when compared to the group carrying the Met-allele. Collectively, this contributes to the identification of central ghrelin pathway as an important modulator in the onset of aggressive behaviours in male mice.
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| 19. |
- Vestlund, Jesper, et al.
(författare)
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Neuromedin U induces self-grooming in socially-stimulated mice.
- 2020
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Ingår i: Neuropharmacology. - : Elsevier BV. - 1873-7064 .- 0028-3908. ; 162
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggest that appetite-regulating peptides modulate social behaviors. We here investigate whether the anorexigenic peptide neuromedin U (NMU) modulates sexual behavior in male mice. However, instead of modulating sexual behaviors, NMU administered into the third ventricle increased self-grooming behavior. In addition, NMU-treatment increased self-grooming behavior when exposed to other mice or olfactory social-cues, but not when exposed to non-social environments. As the neuropeptide oxytocin is released during social investigation and exogenous oxytocin induces self-grooming, its role in NMU-induced self-grooming behavior was investigated. In line with our hypothesis, the oxytocin receptor antagonist inhibited NMU-induced self-grooming behavior in mice exposed to olfactory social-cues. Moreover, dopamine in the mesocorticolimbic system is known to be a key regulator of self-grooming behavior. In line with this, we proved that infusion of NMU into nucleus accumbens increased self-grooming behavior in mice confronted with an olfactory social-cue and that this behavior was inhibited by antagonism of dopamine D2, but not D1/D5, receptors. Moreover repeated NMU treatment enhanced ex vivo dopamine levels and decreased the expression of dopamine D2 receptors in nucleus accumbens in socially housed mice. On the other hand, the olfactory stimuli-dependent NMU-induced self-grooming was not affected by a corticotrophin-releasing hormone antagonist, and NMU-treatment did not influence repetitive behaviors in the marble burying test. In conclusion, our results suggest that NMU treatment and, social cues - potentially triggering oxytocin release - together induce excessive grooming behavior in male mice. The mesolimbic dopamine system, including accumbal dopamine D2 receptors, was identified as a crucial downstream mechanism.
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| 20. |
- Zettergren, Anna, 1978, et al.
(författare)
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Proteomic analyses of limbic regions in neonatal male, female and androgen receptor knockout mice
- 2017
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Ingår i: Bmc Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is well-established that organizational effects of sex steroids during early development are fundamental for sex-typical displays of, for example, mating and aggressive behaviors in rodents and other species. Male and female brains are known to differ with respect to neuronal morphology in particular regions of the brain, including the number and size of neurons, and the density and length of dendrites in nuclei of hypothalamus and amygdala. The aim of the present study was to use global proteomics to identify proteins differentially expressed in hypothalamus/amygdala during early development (postnatal day 8) of male, female and conditional androgen receptor knockout (AR(NesDel)) male mice, lacking androgen receptors specifically in the brain. Furthermore, verification of selected sexually dimorphic proteins was performed using targeted proteomics. Results: Our proteomic approach, iTRAQ, allowed us to investigate expression differences in the 2998 most abundantly expressed proteins in our dissected tissues. Approximately 170 proteins differed between the sexes, and 38 proteins between AR(NesDel) and control males (p < 0.05). In line with previous explorative studies of sexually dimorphic gene expression we mainly detected subtle protein expression differences (fold changes < 1.3). The protein MARCKS (myristoylated alanine rich C kinase substrate), having the largest fold change of the proteins selected from the iTRAQ analyses and of known importance for synaptic transmission and dendritic branching, was confirmed by targeted proteomics as differentially expressed between the sexes. Conclusions: Overall, our results provide solid evidence that a large number of proteins show sex differences in their brain expression and could potentially be involved in brain sexual differentiation. Furthermore, our finding of a sexually dimorphic expression of MARCKS in the brain during development warrants further investigation on the involvement in sexual differentiation of this protein.
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