Study Neurotoxicity by AAS usage (study)

[GrymReefer]

Neurotoxicity by Synthetic Androgen Steroids: Oxidative Stress, Apoptosis, and Neuropathology: A Review

Abstract

Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli.
Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS – induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462038/ And its a free full text!

just something I found while doing some research. Thought it was definitely an interesting read and some of our knowledgeable members would definitely get a kick out of some of the statements. Definitely worth reading. Great information I thought...

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"However, the well known short-term effects of steroids led to hypothesize the existence of other receptors (the so-called non-classical steroid receptors) located within the membrane. The following receptors also act in the same manner: γ-Aminobutyric acid (GABA) type A and B (GABA-A receptor, GABA-B receptor), serotonin type 3 (5-HT3), N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate receptor, and an atypical intracellular receptor like the sigma 1"

"Furthermore, the AAS induced decrease of endogenous neurosteroids biosynthesis, may explain the non-receptor-mediated effects on both aggression and anxiety"

THIS^^many different ideas about the alteration in moods/personality on cycle. May be a good explanation...

 

[CFC]

It was a nice study Grym. I did consider posting it up when pharmbiak mentioned the issues surrounding amyloid plaques from Tren administration. I wasn't sure how many would manage to understand it though.

What did you think? Do you agree with the oxidative stress hypothesis they're putting forward? I generally think it's a good model, and the ambiguity of how the oxidative environment can switch AAS from being neuroprotective to neurotoxic chimes with various other physiological mechanisms.

Also provides further insight into the ambiguous nature of oestrogens and aromatase - protective in the brain relative to a high dose of AAS with high ROS/RNS, damaging in the testes in an environment of similarly high oxidative stress with high AAS.

Thus we control aromatase to inhibit damage to HPTA, but run the risk of increased neurotoxicity in the process.

Which suggests powerful antioxidants like taurine, ALA, NAC - which are nowadays generally (well, sometimes) seen as unhelpful from a holistic health point of view - could be much more essential supplements on any AAS cycle.

 

[GrymReefer]

It was a nice study Grym. I did consider posting it up when pharmbiak mentioned the issues surrounding amyloid plaques from Tren administration. I wasn't sure how many would manage to understand it though.

stress hypothesis they'rWhat did you think? Do you agree with the oxidative e putting forward? I generally think it's a good model, and the ambiguity of how the oxidative environment can switch AAS from being neuroprotective to neurotoxic chimes with various other physiological mechanisms.

Also provides further insight into the ambiguous nature of oestrogens and aromatase - protective in the brain relative to a high dose of AAS with high ROS/RNS, damaging in the testes in an environment of similarly high oxidative stress with high AAS.

Thus we control aromatase to inhibit damage to HPTA, but run the risk of increased neurotoxicity in the process.

Which suggests powerful antioxidants like taurine, ALA, NAC - which are nowadays generally (well, sometimes) seen as unhelpful from a holistic health point of view - could be much more essential supplements on any AAS cycle.

My thought was that this may just be protective response such as a form of achieving homeostasis, but within the neurological system. Like... too many cells responding too vigorously to the supraphysiological androgen levels initiate apoptosis to help as a control measure for the over reactivity that is occuring. Now is this form of apoptosis still considered a "natural" cycle of cell death or is it almost in a form necrotic considering it may be more detrimental? It is also being caused by outside factors which is a contrast to apoptosis and necrosis cell death... I remember seeing something mentioning tumor factors as well.

I'm definitely not as knowledgeable and had to search up individual terms to gain more depth, but thats what learning is about!

 

[CFC]

I'm pretty sure what they're speculating is that these non-AR receptor mediated effects are elevating the oxidative environment and in turn making the supraphysiological amounts of AAS neurotoxic. So it's not really homeostasis, more like a runaway greenhouse effect? Apoptosis usually occurs in an attempt to preserve the functionality of the overall organ/organism - so the cell detects that the shit's hit the fan and attempts to shut down before it makes things worse.

I'll have to do more reading, but I do wonder if calcium channel blockers (which can cross the blood brain barrier) could be further neuroprotective in this situation. So not only would they offset many of the negative cardiovascular side effects caused by AAS from the influx of calcium, but they would also protect cells in the brain. If so, they could really help transform much of the risk factor involved in AAS use.

 

[GrymReefer]

That analogy with the greenhouse effect makes so much sense. You're a great teacher!

Now with the use of antioxidants, some notable ones cause an acidic environment in the body while others contribute more to alkalinity. Would this be a major factor in the function of the cells throughout the body? Considering an acidic pH in the body is associated with stress.

 

[CFC]

The body is actually pretty good at maintaining a balanced pH environment where it's needed and pumping excess H+ ions away in the urine. Obviously eating a shit ton of protein and supplements could make it harder, but if you keep your vegetable intake high, you're really helping to balance that risk. I honestly couldn't say if excess acidity would play any additional part in this scenario though.

 

[Neuroprotection]

Thanks GrymReefer. I have recently read this study, It is amazingly in-depth and very lodgical. While at first I felt it shattered the hope of safe steroid use I soon realised it gave more hope than ever. By highlighting the symple mechanisms behind the neurotoxicity, these can be targeted whilst still gaining the benefits of androgen receptor over activation. In fact, anti-oxidants and caspase inhibitors/calcium channel blockers might not only block neurotoxicity, but bring out the benefits of androgens in the brain.

 

[Intense]

Tren maybe... That's the only one I would think could have an effect.

It was a nice study Grym. I did consider posting it up when pharmbiak mentioned the issues surrounding amyloid plaques from Tren administration. I wasn't sure how many would manage to understand it though.

What did you think? Do you agree with the oxidative stress hypothesis they're putting forward? I generally think it's a good model, and the ambiguity of how the oxidative environment can switch AAS from being neuroprotective to neurotoxic chimes with various other physiological mechanisms.

Also provides further insight into the ambiguous nature of oestrogens and aromatase - protective in the brain relative to a high dose of AAS with high ROS/RNS, damaging in the testes in an environment of similarly high oxidative stress with high AAS.

Thus we control aromatase to inhibit damage to HPTA, but run the risk of increased neurotoxicity in the process.

Which suggests powerful antioxidants like taurine, ALA, NAC - which are nowadays generally (well, sometimes) seen as unhelpful from a holistic health point of view - could be much more essential supplements on any AAS cycle.

CDP-Choline is another great one.