Brain nerve growth factor unbalance induced by anabolic androgenic steroids in rats.
OBJECTIVE
Anabolic androgenic steroids (AAS) are synthetic androgen-like compounds that are abused in sport communities despite their adverse effects. Nerve growth factor (NGF) influences neuronal differentiation and survival, and it also mediates higher brain functions such as learning and memory. Changes in NGF expression have been implicated in neurodegenerative disorders, including Alzheimer disease. Hence, we decided to study the effect of chronic AAS exposure on brain NGF profile, NGF-dependent cholinergic function, and related behavioral performance.


METHODS
Male Wistar rats were injected for 4 wk with either nandrolone or stanozolol at daily doses (5.0 mg·kg(-1), s.c.) that are considered equivalent to those abused by humans. NGF levels and NGF receptor (TrkA and p75NTR) expression were measured in the hippocampus and in the basal forebrain. Choline acetyltransferase expression was evaluated in basal forebrain. Spatial learning and memory were assessed using the Morris water maze.


RESULTS
AAS treatment caused region-specific changes in the expression of NGF and its receptors. Both nandrolone and stanozolol increased NGF levels in the hippocampus and reduced NGF levels in the basal forebrain, reduced p75NTR expression in the hippocampus, and failed to affect TrkA expression in the basal forebrain. Finally, AAS treatment reduced the expression of choline acetyltransferase in the basal forebrain and impaired the behavioral performance in the Morris water maze.


CONCLUSIONS
The evidence that supraphysiological doses of AAS cause neurotrophic unbalance and related behavioral disturbances raises the concern that AAS abuse in humans may affect mechanisms that lie at the core of neuronal plasticity.
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Stefano
S
Pieretti
Marica
M
Mastriota
Paolo
P
Tucci
Giuseppe
G
Battaglia
Luigia
L
Trabace
Ferdinando
F
Nicoletti
Sergio
S
Scaccianoce
D045930:Anabolic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000728:Androgens / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009277:Nandrolone / Q000008:administration & dosage / Q000009:adverse effects*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D058573:Performance-Enhancing Substances / Q000008:administration & dosage / Q000009:adverse effects*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013197:Stanozolol / Q000008:administration & dosage / Q000009:adverse effects*
D045930:Anabolic Agents; D000728:Androgens; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D058573:Performance-Enhancing Substances; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; D013197:Stanozolol; D009277:Nandrolone; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA