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Rodolphi 2017 Thesis
Additional label 2017-08  +
Coupling states ROUTINE  + , OXPHOS  +
Has abstract Anabolic androgenic steroids (AAS) such as
Anabolic androgenic steroids (AAS) such as nandrolone decanoate (ND) are synthetic hormones derived from testosterone. It is known that one of the most important adverse effects of abusive administration of these steroids is the increase in aggressive behavior. Evidence indicates that high doses of AAS alter morphology and cause hyperactivation of glutamatergic synapses which correlates with an aggressive exacerbated phenotype. Physiologically, glutamate is considered the main excitatory neurotransmitter in the mammalian brain. At high glutamate levels, occurs neuronal hyperexcitability mainly through the ionotropic N-methyl-d-aspartate (NMDAr) type of glutamatergic receptors and, consequently, changes in mitochondrial metabolism. Existing transporters in astrocytes predominantly perform the termination of glutamatergic excitatory signaling. In this sense, the GLT-1 glutamate astrocytic transporter is responsible for more than 90% of glutamate removal from the synaptic cleft, contributing significantly to the maintenance of glutamatergic signaling homeostasis. Administration of the β-lactam antibiotic ceftriaxone (CEF) increases GLT-1 expression and decreases glutamatergic hyperexcitability, which could potentially counteract brain mechanisms associated to increased aggressive phenotype mediated by nandrolone decanoate (ND). However, a possible molecular and behavioral interaction has not yet been explored in context. Thus, the primary objective of this work was to investigate whether increased expression of the GLT-1 astrocyte transporter modulates the glutamatergic mechanisms involved in ND-induced aggressive phenotype, and mitochondrial activity. Sixty-day-old male CF-1 mice were divided into 4 groups: oil vehicle (VEH), nandrolone (ND), ceftriaxone (CEF) and nandrolone + ceftriaxone (ND / CEF). Nandrolone was injected subcutaneously (15mg / kg) for 19 days. Ceftriaxone (200mg / kg) or saline solution were administered intraperitoneally for 5 days. After the last injection, the latency for the first attack and the number of attacks on the intruder test were evaluated. The animals were sacrificed after the test, and homogeinized cortex were used for immunoquantification of GLT-1 and phosphorylation of the NMDAr pNR2B<sup>ser1232</sup> subunit. Mitochondrial activity was evaluated in total brain sinaptossomes. Glutamate levels were measured in the cerebrospinal fluid. Compared to the vehicle group, treatment with ND significantly decreased the expression of GLT-1, increased glutamate levels and expression of the pNR2B<sup>ser1232</sup> which was mechanistically associated with an increase in the aggressive phenotype; decrease in the latency and increase in the number of attacks. Also, ND decreased mitochondrial respiratory control. Administration of CEF significantly increased GLT-1 expression and decreased glutamate levels relative to the ND group, whereas pNR2B<sup>ser1232</sup> levels and aggressive phenotype were similar to the control group. In the ND / CEF group the expression of GLT-1 and pNR2B<sup>ser1232</sup>, glutamate levels and aggressive phenotype were significantly lower than in the ND group, and similar to the control group. Furthermore, CEF was able to attenuate the alteration in the mitochondrial respiratory control caused by ND. Our results demonstrated that the levels of glutamate astrocytic transporter GLT-1 and pNR2B<sup>ser1232</sup> are important mechanism behind the increased aggressive phenotype induced by ND, and decreased mitochondrial respiratory control. Also, this model reinforces the importance of glutamate levels and astrocytic molecular targets in the regulation of the aggressive phenotype.
he regulation of the aggressive phenotype.  +
Has editor [[Kandolf G]]  +
Has info [http://www.lume.ufrgs.br/handle/10183/157966 Open Access]  +
Has publicationkeywords Androgenic anabolic steroids  + , Glutamate  + , Ceftriaxone  + , GLT-1  + , NMDAr  + , Mitochondria  +
Has title Rodolphi MS (2017) Efeitos da nandrolona e da ceftriaxona na homeostasia glutamatérgica: uma busca por mecanismos interativos entre astrócitos e neurônios envolvidos no comportamento agressivo. Dissertation p58.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Pharmacology;toxicology  +
Pathways S  + , CIV  + , ROX  +
Preparation Homogenate  +
Tissue and cell Nervous system  +
Was published by MiPNetLab BR Porto Alegre Souza DOG +
Was published in journal Dissertation +
Was published in year 2017  +
Was written by Rodolphi MS +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
09:35:25, 27 June 2019  +
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