Sexual responses of male rats to odours from female rats in oestrus are not affected by female germ-free status

Nielsen, Birte L.; Jerome, Nathalie; Saint-Albin, Audrey; Joly, Fatima; Rabot, Sylvie; Meunier, Nicolas

doi:10.1016/j.bbr.2018.09.018

Cited by 9 publications

(9 citation statements)

References 55 publications

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“…To normalize for urine output, levels were divided by urinary creatinine levels measured with the QuantiChromTM Creatinine kit (BioAssay Systems). The assays were carried out at Nordic Bioscience laboratories following previously described protocols Nielsen et al 2013Nielsen et al , 2018Bager et al 2016;Genovese et al 2016). Briefly, astreptavidin-coated 96-well ELISA plates (Roche, Cat.…”

Section: Biomarkers Of Ecm Formation and Degradationmentioning

confidence: 99%

“…; Nielsen et al . ). Numerous recent studies have confirmed the association of urinary C3M (uC3M) with renal fibrosis in different rat models including 5/6 Nx, anti‐Thy 1.1, adenine nephropathy and type 2 diabetic nephropathy models (Papasotiriou et al .…”

Section: Introductionmentioning

confidence: 97%

“…The formation and degradation of ECM components lead to specific pro-collagen terminal fragments and protein neo-epitopes secreted into urine (Genovese et al 2014), which have recently been discovered as novel, early urinary biomarkers of renal fibrosis. Two of them are neo-epitopes of MMP-9-mediated degradation of type III collagen (C3M) and type IV collagen alpha 3 chain known as tumstatin (TUM) (Genovese et al 2016;Nielsen et al 2018). Numerous recent studies have confirmed the association of urinary C3M (uC3M) with renal fibrosis in different rat models including 5/6 Nx, anti-Thy 1.1, adenine nephropathy and type 2 diabetic nephropathy models (Papasotiriou et al 2015;Dower et al 2017).…”

Section: Introductionmentioning

confidence: 99%

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RAAS inhibitors directly reduce diabetes‐induced renal fibrosis via growth factor inhibition

Kőszegi

Molnár

Lionetti

et al. 2018

The Journal of Physiology

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Key points Increased activation of the renin‐angiotensin‐aldosterone system (RAAS) and elevated growth factor production are of crucial importance in the development of renal fibrosis leading to diabetic kidney disease.The aim of this study was to provide evidence for the antifibrotic potential of RAAS inhibitor (RAASi) treatment and to explore the exact mechanism of this protective effect.We found that RAASi ameliorate diabetes‐induced renal interstitial fibrosis and decrease profibrotic growth factor production.RAASi prevents fibrosis by acting directly on proximal tubular cells, and inhibits hyperglycaemia‐induced growth factor production and thereby fibroblast activation.These results suggest a novel therapeutic indication and potential of RAASi in the treatment of renal fibrosis. AbstractIn diabetic kidney disease (DKD) increased activation of renin‐angiotensin‐aldosterone system (RAAS) contributes to renal fibrosis. Although RAAS inhibitors (RAASi) are the gold standard therapy in DKD, the mechanism of their antifibrotic effect is not yet clarified. Here we tested the antifibrotic and renoprotective action of RAASi in a rat model of streptozotocin‐induced DKD. In vitro studies on proximal tubular cells and renal fibroblasts were also performed to further clarify the signal transduction pathways that are directly altered by hyperglycaemia. After 5 weeks of diabetes, male Wistar rats were treated for two more weeks per os with the RAASi ramipril, losartan, spironolactone or eplerenone. Proximal tubular cells were cultured in normal or high glucose (HG) medium and treated with RAASi. Platelet‐derived growth factor (PDGF) or connective tissue growth factor (CTGF/CCN2)‐induced renal fibroblasts were also treated with various RAASi. In diabetic rats, reduced renal function and interstitial fibrosis were ameliorated and elevated renal profibrotic factors (TGFβ1, PDGF, CTGF/CCN2, MMP2, TIMP1) and alpha‐smooth muscle actin (αSMA) levels were decreased by RAASi. HG increased growth factor production of HK‐2 cells, which in turn induced activation and αSMA production of fibroblasts. RAASi decreased tubular PDGF and CTGF expression and reduced production of extracellular matrix (ECM) components in fibroblasts. In proximal tubular cells, hyperglycaemia‐induced growth factor production increased renal fibroblast transformation, contributing to the development of fibrosis. RAASi, even in non‐antihypertensive doses, decreased the production of profibrotic factors and directly prevented fibroblast activation. All these findings suggest a novel therapeutic role for RAASi in the treatment of renal fibrosis.

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Section: Biomarkers Of Ecm Formation and Degradationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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RAAS inhibitors directly reduce diabetes‐induced renal fibrosis via growth factor inhibition

Kőszegi

Molnár

Lionetti

et al. 2018

The Journal of Physiology

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“…Although freezing is often considered an indication of fear, the behaviour is but a display of increased alertness, and the interpretation is context specific. Exposure to oestrus odours can elicit freezing in rats [30,45] and this is enhanced by sexual experience [31]. It may be that odour A induced freezing in control rats because they find it more interesting, as shown by their un-conditioned preference in the T-maze test.…”

Section: Discussionmentioning

confidence: 99%

Odour conditioning of positive affective states: Rats can learn to associate an odour with being tickled

et al. 2019

Self Cite

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Most associative learning tests in rodents use negative stimuli, such as electric shocks. We investigated if young rats can learn to associate the presence of an odour with the experience of being tickled (i.e. using an experimenter’s hand to mimic rough-and-tumble play), shown to elicit 50 kHz ultrasonic vocalisations (USVs), which are indicative of positive affect. Male, pair-housed Wistar rats (N = 24) were all exposed to two neutral odours (A and B) presented in a perforated container on alternate days in a test arena. Following 60s of exposure, the rats were either tickled on days when odour A (n = 8) or odour B (n = 8) was present, or never tickled (n = 8). When tickled, rats produced significantly more 50 kHz USVs compared to the days when not being tickled, and compared to control rats. The level of anticipatory 50 kHz USVs in the 60s prior to tickling did not differ significantly between the tickled and control rats. As a retrieval test following the odour conditioning, rats were exposed successively in the same arena to three odours: an unknown neutral odour, extract of fox faeces, and either odours A or B. Compared to controls, 50 kHz USVs of tickled rats increased when exposed to the odour they had previously experienced when tickled, indicating that these rats had learned to associate the odour with the positive experience of being tickled. In a test with free access for 5 min to both arms of a T-maze, each containing one of the odours, rats tickled with odour A spent more time in the arm with this odour. This work is the first to test in a fully balanced design whether rats can learn to associate an odour with tickling, and indicates that positive odour conditioning has potential to be used as an alternative to negative conditioning tests.

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“…Exposure to oestrus odours can elicit freezing in rats (Nielsen et al, 2013(Nielsen et al, , 2019 and this is enhanced…”

mentioning

confidence: 99%

Odour conditioning of positive affective states: Rats can learn to associate an odour with being tickled

Bombail

Jerome

Lam

et al. 2019

Preprint

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Most associative learning tests in rodents use negative stimuli, such as an electric shock. We investigated if young rats can learn to associate the presence of an odour with the experience of being tickled (i.e. using an experimenter’s hand to mimic rough-and-tumble play), shown to elicit 50 kHz ultrasonic vocalisations (USVs), which are indicative of positive affect. Male, pair-housed Wistar rats (N=24) were all exposed to two neutral odours (A and B) presented in a perforated container on alternate days in a test arena. Following 60s of exposure, the rats were either tickled on days when odour A (n=8) or odour B (n=8) was present, or never tickled (n=8). When tickled, rats produced significantly more 50 kHz USVs compared to the days when not being tickled, and compared to control rats. The level of anticipatory 50 kHz USVs in the 60s prior to tickling did not differ significantly between the tickled and control rats. Following the odour conditioning, rats were exposed successively in the same arena to three odours: an unknown neutral odour, extract of fox faeces, and either odours A or B. Compared to controls, 50 kHz USVs of tickled rats increased when exposed to the odour they had previously experienced when tickled, indicating that these rats had learned to associate the odour with the positive experience of being tickled. In a test with free access for 5 min to both arms of a T-maze, each containing one of the odours, rats tickled with odour A spent more time in the arm with this odour. This work is the first to test in a fully balanced design whether odours can be conditioned to tickling, and indicates that positive odour conditioning has potential to be used as an alternative to negative conditioning tests.

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Sexual responses of male rats to odours from female rats in oestrus are not affected by female germ-free status

Cited by 9 publications

References 55 publications

RAAS inhibitors directly reduce diabetes‐induced renal fibrosis via growth factor inhibition

RAAS inhibitors directly reduce diabetes‐induced renal fibrosis via growth factor inhibition

Odour conditioning of positive affective states: Rats can learn to associate an odour with being tickled

Odour conditioning of positive affective states: Rats can learn to associate an odour with being tickled

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