The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids

Gomes, Fabiano Guimarães Novaes; Fernandes, Jansen; Campos, Diego Vannucci; Cassilhas, Ricardo Cardoso; Viana, Gustavo Monteiro; D’Almeida, Vânia; Rêgo, Marta Karavisch de Moraes; Buainain, Pedro I.; Cavalheiro, Ésper A.; Arida, Ricardo Mário

doi:10.1016/j.psyneuen.2014.08.009

Cited by 51 publications

(41 citation statements)

References 66 publications

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“…One of these tests, Paired Associates Learning, has previously been shown to predict the development of dementia (Swainson et al, 2001). Consistent with our human findings, rodent studies have shown that AAS exposure can impair performance on the Morris water maze test of spatial learning and memory (Magnusson et al, 2009; Novaes Gomes et al, 2014; Pieretti et al, 2012; Tanehkar et al, 2013). Impaired inhibitory control and attention also were recently reported in men actively taking AAS, with greater impairment found in adolescent- than adult-onset AAS users (Hildebrandt et al, 2014).…”

Section: Introductionsupporting

confidence: 90%

“…Our negative finding could have resulted if AAS-induced abnormalities are limited to dentate gyrus granule cells, the neurogenesis of which is inhibited by AAS (Brannvall et al, 2005; Novaes Gomes et al, 2014). Since dentate gyrus volume averages less than 5% of total hippocampal volume (Boldrini et al, 2013; McKinnon et al, 2009), even large dentate gyrus volume changes might have gone undetected with the present methods, which had a variability (standard deviation) of about 8% for whole hippocampus measurement.…”

Section: Discussionmentioning

confidence: 83%

“…The hippocampus is involved in spatial memory processes (Squire, 1992). In rats, AAS induce hippocampal apoptosis (Ma and Liu, 2015; Tugyan et al, 2013), and inhibit hippocampal neurogenesis (Brannvall et al, 2005; Novaes Gomes et al, 2014), suggesting that AAS could reduce hippocampal volume, which could be a basis for the AAS-associated spatial memory impairments observed in human and animal studies. The dACC is a cognitive control region involved in attentional processes (Bush and Shin, 2006), which as noted above are abnormal in human AAS users (Hildebrandt et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Brain and cognition abnormalities in long-term anabolic-androgenic steroid users

Kaufman

Janes

Hudson

et al. 2015

Drug and Alcohol Dependence

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Background Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans. Methods This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS). Results AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053). Conclusions Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction.

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Section: Introductionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Brain and cognition abnormalities in long-term anabolic-androgenic steroid users

Kaufman

Janes

Hudson

et al. 2015

Drug and Alcohol Dependence

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“…Conversely, experimental evidences have demonstrated that both aerobic and anaerobic exercises can significantly increase neuronal proliferation in these regions, an effect that has been correlated to the improved mnemonic capacity and neuronal survival [128,129]. In this context, rats submitted to strength exercise in a vertical ladder showed up-regulation of Ki-67 throughout the dentate gyrus, which is considered a marker of neurogenesis [130]. However, chronic administration of nandrolone decanoate abolished this effect, suggesting that AS abuse can decrease the neurogenic effect induced by exercise.…”

Section: Long-term As Abuse and Cognitive Impairmentsmentioning

confidence: 99%

Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

Seara¹,

Fortunato²,

Carvalho³

et al. 2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Since its discovery, several chemical modifications in the testosterone molecule have been done by pharmaceutical industry in order to improve its pharmacological effects, resulting in the creation of anabolic steroids (AS). Despite the therapeutic benefits, AS abuse has spread among elite and recreational athletes in the search for improvements on physical appearance and physical performance. Illicit use of anabolic AS has been correlated with several adverse effects, such as cardiovascular, endocrine, reproductive, and neurobehavioral dysfunctions. Recently, declines on cognitive and mnemonic performance have been demonstrated clinically and experimentally. Experimental studies have demonstrated that these neurological dysfunctions are correlated to spread neuronal apoptosis throughout important areas of the central nervous system (CNS), such as hippocampus and cortex. Several pathophysiological mechanisms have been linked to the AS-induced neurotoxicity, including redox imbalance and recruitment of pro-apoptotic downstream pathways. Furthermore, exposure to AS has arisen as a potential risk factor to the development of Alzheimer's disease. Altogether, these evidences imply that AS abuse per se induces neurodegeneration and can aggravate the prognosis of neurodegenerative diseases.

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“…Few studies have assessed potential neural mechanisms underlying the interactions of AAS and exercise in the expression of anxiety, but those that have been performed point to regulation in the hippocampus as having an important role. For example, Gomes et al (2014) reported that anti-apoptotic and pro-proliferative processes in the hippocampus that were elicited by strength exercise and were presumed to contribute to the anxiolytic actions of exercise were impaired by AAS exposure in adult male rats. In male mice, both wheel running and AAS influenced the levels of mRNA encoding the presumed anxiolytic molecule, brain-derived neurotrophic factor (BDNF; Pedersen et al 2009; Zoladz and Pilc 2010; Novak et al 2012) when mice were treated during adolescence; however, the interactions of AAS and exercise did not necessarily correlate well with changes in hippocampal BDNF mRNA (Onakomaiya et al 2014).…”

Section: Interactions Of Aas and Exercisementioning

confidence: 99%

Mad men, women and steroid cocktails: a review of the impact of sex and other factors on anabolic androgenic steroids effects on affective behaviors

Onakomaiya

Henderson

2016

Psychopharmacology

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Rationale For several decades, elite athletes and a growing number of recreational consumers have used anabolic androgenic steroids (AAS) as performance enhancing drugs. Despite mounting evidence that illicit use of these synthetic steroids has detrimental effects on affective states, information available on sex-specific actions of these drugs is lacking. Objectives The focus of this review is to assess information to date on the importance of sex and its interaction with other environmental factors on affective behaviors, with an emphasis on data derived from non-human studies. Methods The PubMed database was searched for relevant studies in both sexes. Results Studies examining AAS use in females are limited, reflecting the lower prevalence of use in this sex. Data, however, indicate significant sex-specific differences in AAS effects on anxiety-like and aggressive behaviors, interactions with other drugs of abuse, and the interplay of AAS with other environmental factors such as diet and exercise. Conclusions Current methods for assessing AAS use have limitations that suggest biases of both under- and over-reporting, which may be amplified for females who are poorly represented in self-report studies of human subjects and are rarely used in animal studies. Data from animal literature suggest that there are significant sex-specific differences in the impact of AAS on aggression, anxiety, and concomitant use of other abused substances. These results have relevance for human females who take these drugs as performance enhancing substances and for transgender XX individuals who may illicitly self-administer AAS as they transition to a male gender identity.

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The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids

Cited by 51 publications

References 66 publications

Brain and cognition abnormalities in long-term anabolic-androgenic steroid users

Brain and cognition abnormalities in long-term anabolic-androgenic steroid users

Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

Mad men, women and steroid cocktails: a review of the impact of sex and other factors on anabolic androgenic steroids effects on affective behaviors

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