eazy
Well-known member
Main Mechanisms of AAS Neurotoxicity
1. Apoptosis (Programmed Neuronal Death)
High-dose AAS trigger apoptotic pathways in neurons.
Mechanisms include:
Activation of caspase-dependent pathways.
Mitochondrial dysfunction leading to cytochrome c release.
Ca²⁺ (intracellular messenger that controls diverse cellular functions) overload, triggering intrinsic cell death pathways.
Demonstrated in multiple models (neuroblastoma cells, cortical neurons, PC12 cells).
2. Oxidative Stress
AAS increase reactive oxygen/nitrogen species (ROS/RNS), damaging cellular proteins, DNA, and lipids.
Oxidative stress links strongly to:
Mitochondrial damage
Apoptosis (the process of programmed cell death)
Excitotoxicity (especially via NMDA receptor overactivation)
Evidence suggests androgens are neuroprotective at physiological levels, but neurotoxic under oxidative stress.
3. Excitotoxicity
AAS enhance neuronal vulnerability to glutamate excitotoxicity, increasing Ca²⁺ influx via NMDA receptors.
Low testosterone may protect, but supraphysiologic doses amplify NMDA toxicity.
4. Neurotrophin Imbalance
Chronic AAS administration alters brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) signaling.
Results in reduced neuronal plasticity and possible depressive-like behavior.
5. HPA Axis & Monoamine Changes
Chronic AAS use alters corticosterone, dopamine, and serotonin regulation in the hippocampus and prefrontal cortex — biochemically mimicking depressive states.
Neuroprotective Findings (Context-Dependent)
Physiological androgen levels can support neuronal survival and differentiation.
However, when oxidative stress is already elevated, androgens exacerbate cell death.
The effect is dose- and context-dependent — possibly biphasic (protective → toxic).
Clinical Implications
Chronic AAS users may face latent neurodegenerative risk, including cognitive decline, visuospatial deficits, and mood instability.
These effects may remain clinically silent until middle age due to delayed neurodegenerative progression.
Treatment
Target oxidative stress, excitotoxicity, and apoptosis pathways with neuroprotective and antioxidant treatments.
Cessation, nutritional correction, psychological care, and potentially epigenetic modulation or mitochondrial-targeted interventions.
TLDR:
Anabolic–androgenic steroids (AAS) — when abused at high, nonmedical doses — can damage the brain through oxidative stress and apoptosis.
Normal testosterone levels help the brain function and protect neurons.
Too much AAS for too long flips that benefit — it causes oxidative stress, mitochondrial damage, and cell death in neurons.
This leads to mood changes, aggression, depression, and possibly long-term cognitive decline.
The damage often builds silently over time and may not show up until years later.
The key driver is oxidative stress — once that’s triggered, androgens that were once protective become toxic.
Oxidative stress is a biological imbalance between the production of reactive oxygen species (ROS) — harmful molecules like free radicals — and the body’s ability to neutralize or repair their effects using antioxidants.
In simple terms:
It’s what happens when your cells make more “oxidants” (chemical sparks) than your defenses can handle — those sparks start burning holes in your DNA, proteins, and cell membranes.
When oxidative stress lasts too long, it can damage tissues throughout the body — including the brain, where it contributes to aging, neurodegeneration, and AAS-related toxicity.
Here’s how oxidative stress damages brain cells, step by step:
Reactive oxygen species (ROS) build up — things like superoxide, hydrogen peroxide, and hydroxyl radicals. These molecules are highly unstable and attack nearby structures to steal electrons.
Mitochondria — the cell’s power plants — are the main source and target.
When steroids, drugs, or toxins overload mitochondria, they start leaking ROS.
The damage spirals: damaged mitochondria make more ROS, which further damages them.
Cell membranes are oxidized.
Lipid peroxidation breaks down the fatty layers that protect neurons.
This disrupts how electrical signals travel along nerves and how neurotransmitters are released.
Proteins and enzymes are altered.
ROS can “rust” proteins, changing their shape or disabling them.
This interferes with normal metabolism, signaling, and energy balance in neurons.
DNA and RNA are attacked.
Oxidative stress causes mutations or strand breaks in genetic material.
Cells either misfire, malfunction, or trigger self-destruction (apoptosis).
Neuroinflammation follows.
Damaged neurons release danger signals that activate microglia (the brain’s immune cells).
Chronic microglial activation adds even more oxidative and inflammatory stress.
End result: neurons die or lose function.
Over time, brain regions involved in emotion, motivation, and cognition—like the hippocampus and prefrontal cortex—shrink or weaken.
Clinically, this can show up as memory problems, depression, irritability, or slowed thinking.
SOURCE:
Neurotoxicity by Synthetic Androgen Steroids: Oxidative Stress, Apoptosis, and Neuropathology: A Review
pmc.ncbi.nlm.nih.gov
1. Apoptosis (Programmed Neuronal Death)
High-dose AAS trigger apoptotic pathways in neurons.
Mechanisms include:
Activation of caspase-dependent pathways.
Mitochondrial dysfunction leading to cytochrome c release.
Ca²⁺ (intracellular messenger that controls diverse cellular functions) overload, triggering intrinsic cell death pathways.
Demonstrated in multiple models (neuroblastoma cells, cortical neurons, PC12 cells).
2. Oxidative Stress
AAS increase reactive oxygen/nitrogen species (ROS/RNS), damaging cellular proteins, DNA, and lipids.
Oxidative stress links strongly to:
Mitochondrial damage
Apoptosis (the process of programmed cell death)
Excitotoxicity (especially via NMDA receptor overactivation)
Evidence suggests androgens are neuroprotective at physiological levels, but neurotoxic under oxidative stress.
3. Excitotoxicity
AAS enhance neuronal vulnerability to glutamate excitotoxicity, increasing Ca²⁺ influx via NMDA receptors.
Low testosterone may protect, but supraphysiologic doses amplify NMDA toxicity.
4. Neurotrophin Imbalance
Chronic AAS administration alters brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) signaling.
Results in reduced neuronal plasticity and possible depressive-like behavior.
5. HPA Axis & Monoamine Changes
Chronic AAS use alters corticosterone, dopamine, and serotonin regulation in the hippocampus and prefrontal cortex — biochemically mimicking depressive states.
Neuroprotective Findings (Context-Dependent)
Physiological androgen levels can support neuronal survival and differentiation.
However, when oxidative stress is already elevated, androgens exacerbate cell death.
The effect is dose- and context-dependent — possibly biphasic (protective → toxic).
Clinical Implications
Chronic AAS users may face latent neurodegenerative risk, including cognitive decline, visuospatial deficits, and mood instability.
These effects may remain clinically silent until middle age due to delayed neurodegenerative progression.
Treatment
Target oxidative stress, excitotoxicity, and apoptosis pathways with neuroprotective and antioxidant treatments.
Cessation, nutritional correction, psychological care, and potentially epigenetic modulation or mitochondrial-targeted interventions.
TLDR:
Anabolic–androgenic steroids (AAS) — when abused at high, nonmedical doses — can damage the brain through oxidative stress and apoptosis.
Normal testosterone levels help the brain function and protect neurons.
Too much AAS for too long flips that benefit — it causes oxidative stress, mitochondrial damage, and cell death in neurons.
This leads to mood changes, aggression, depression, and possibly long-term cognitive decline.
The damage often builds silently over time and may not show up until years later.
The key driver is oxidative stress — once that’s triggered, androgens that were once protective become toxic.
Oxidative stress is a biological imbalance between the production of reactive oxygen species (ROS) — harmful molecules like free radicals — and the body’s ability to neutralize or repair their effects using antioxidants.
In simple terms:
It’s what happens when your cells make more “oxidants” (chemical sparks) than your defenses can handle — those sparks start burning holes in your DNA, proteins, and cell membranes.
When oxidative stress lasts too long, it can damage tissues throughout the body — including the brain, where it contributes to aging, neurodegeneration, and AAS-related toxicity.
Here’s how oxidative stress damages brain cells, step by step:
Reactive oxygen species (ROS) build up — things like superoxide, hydrogen peroxide, and hydroxyl radicals. These molecules are highly unstable and attack nearby structures to steal electrons.
Mitochondria — the cell’s power plants — are the main source and target.
When steroids, drugs, or toxins overload mitochondria, they start leaking ROS.
The damage spirals: damaged mitochondria make more ROS, which further damages them.
Cell membranes are oxidized.
Lipid peroxidation breaks down the fatty layers that protect neurons.
This disrupts how electrical signals travel along nerves and how neurotransmitters are released.
Proteins and enzymes are altered.
ROS can “rust” proteins, changing their shape or disabling them.
This interferes with normal metabolism, signaling, and energy balance in neurons.
DNA and RNA are attacked.
Oxidative stress causes mutations or strand breaks in genetic material.
Cells either misfire, malfunction, or trigger self-destruction (apoptosis).
Neuroinflammation follows.
Damaged neurons release danger signals that activate microglia (the brain’s immune cells).
Chronic microglial activation adds even more oxidative and inflammatory stress.
End result: neurons die or lose function.
Over time, brain regions involved in emotion, motivation, and cognition—like the hippocampus and prefrontal cortex—shrink or weaken.
Clinically, this can show up as memory problems, depression, irritability, or slowed thinking.
SOURCE:
Neurotoxicity by Synthetic Androgen Steroids: Oxidative Stress, Apoptosis, and Neuropathology: A Review
Neurotoxicity by Synthetic Androgen Steroids: Oxidative Stress, Apoptosis, and Neuropathology: A Review - PMC
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, ...
pmc.ncbi.nlm.nih.gov
