Glutamate transporter-1 link astrocytes with heightened aggressive behavior induced by steroid abuse in male CF1 mice

Rodolphi, Marcelo Salimen; Kopczynski, Afonso; Carteri, Randhall Bruce; Sartor, Mônia; Fontella, Fernanda U.; Feldmann, Marceli; Hansel, Gisele; Strogulski, Nathan Ryzewski; Portela, Luis Valmor

doi:10.1016/j.yhbeh.2020.104872

Cited by 7 publications

(3 citation statements)

References 55 publications

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“…Albino CF1 mice of 3 and 18 months of age were randomly selected to receive either subcutaneous administration of a synthetic analog of testosterone, nandrolone decanoate (18m/ND) (Decadurabolin ® , Schering-Plough, Brazil) at a dose of 15 mg/kg, or an equivalent volume of vehicle (Corn oil, Salada ™ , Bunge, Brazil) once a day for 15 consecutive days [24,28]. Animals were maintained in plexiglass cages, with an average of 4 littermates, and ad libitum access to water and standard chow under controlled temperature (22 ±1 °C) and lighting (12 h light/12 h dark, lights on at 7 am) conditions.…”

Section: Animal Proceduresmentioning

confidence: 99%

“…The reported decrease in AAS during the course of aging has been the mechanistic basis for proposing exogenous hormone administration to hamper age-related physiological deficits [17][18][19][20][21]. Testosterone and its synthetic derivative nandrolone decanoate (ND) induce robust anabolic effects in various tissues, including the brain [22][23][24]. Based on these properties, administration of AAS has already been investigated to attenuate age-related brain pathologies, in which a decrease in bioenergetic function exerts a role in the progression of symptoms and the severity of disease [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice

et al. 2022

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Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18 FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14 th day, 18 FDG-mPET analyses were performed. Hypothalamic pAMPK T172 /AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18 FDG uptake. We found that ND increased the pAMPK T172 /AMPK ratio in both adult and aged mice but induced 18 FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.

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Section: Animal Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice

et al. 2022

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“…However, although testosterone synthetic analogs replacement therapy has been considered to decrease aging processes, its potential benefits to cerebral connectivity, hypothalamic mechanisms of metabolic control during ageing remains elusive, as well as if these effects are impacted by ageing. Nandrolone Decanoate, is a synthetic analog of testosterone, with robust anabolic effect, that has been previously shown to promote adaptations in synaptic bioenergetics and function [15][16][17] . Further, the administration of androgen hormones has already been investigated to attenuate cognitive damage following brain injury 18 .…”

Section: Introductionmentioning

confidence: 99%

Nandrolone supplementation promotes AMPK activation and divergent¹⁸[FDG] PET brain connectivity in adult and aged mice

Strogulski

Kopczynski²,

Girelli³

et al. 2021

Preprint

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Abnormalities in energetic and proteic homeostasis during ageing relate to neurodegenerative diseases. The mitochondria are a hub of oxidative metabolism, influencing autophagic flux. Ageing can lead to a functional disruption of these systems, leading to neuroenergetic and proteotoxic imbalance. Lower levels of testosterone have been proposed as a mechanism accelerating functional decline during ageing. In this study we investigated whether nandrolone decanoate (ND), an analog of testosterone, in aged animals improves mitochondrial bioenergetics and autophagy. Albino CF1 mice of 3 and 18 months of age, were separated in 4 groups that received daily subcutaneous injections for 15 days of either ND (15mg/kg), or vehicle. Were performed baseline and 14th day 18FDG uptake analysis, through positron emission tomography scan. High resolution respirometry was performed to assess functionally mitochondrial respiratory states and respiratory control ratio (RCR) in synaptossomes fractions. Also, hypothalamic immunocontent of AMPK, pAMPKT172, Beclin-1 and BCL-2 LC3 was assessed. Results demonstrate that aged animals did not display alterations nor in 18FDG uptake, neither in mitochondrial respiratory states. Also, aged mice displayed reduced pAMPKT172/ AMPK ratio, and increased LC3-II compared to adult controls. Curiously, ND in aged mice did neither increase 18FDG uptake, nor alter mitochondrial states. Albeit, ND increased pAMPKT172/ AMPK ratio, LC3-II turnover, as well as increased RCR. This suggest that ageing does not culminate necessarily in bioenergetics alterations in brain, although biomarkers of energetic status and autophagy are reduced. ND improved bioenergetic efficiency and autophagy in aged mice. These benefits are probably mediated by reprogramation of AMPK signalling.

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Synaptic and Extrasynaptic Mitochondria

Oliveira

Justus

Portela

et al. 2022

Handbook of Substance Misuse and Addictions

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Glutamate transporter-1 link astrocytes with heightened aggressive behavior induced by steroid abuse in male CF1 mice

Cited by 7 publications

References 55 publications

Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice

Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice

Nandrolone supplementation promotes AMPK activation and divergent¹⁸[FDG] PET brain connectivity in adult and aged mice

Synaptic and Extrasynaptic Mitochondria

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Glutamate transporter-1 link astrocytes with heightened aggressive behavior induced by steroid abuse in male CF1 mice

Cited by 7 publications

References 55 publications

Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice

Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice

Nandrolone supplementation promotes AMPK activation and divergent18[FDG] PET brain connectivity in adult and aged mice

Synaptic and Extrasynaptic Mitochondria

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Nandrolone supplementation promotes AMPK activation and divergent¹⁸[FDG] PET brain connectivity in adult and aged mice