Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus.
During adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal-dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult-generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult-generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.
Dupret
David
D
INSERM U588, University of Bordeaux II, Institute F Magendie, 146 rue Léo-Saignat, 33077 Bordeaux Cedex, France.
Montaron
Marie-Françoise
MF
Drapeau
Elodie
E
Aurousseau
Catherine
C
Le Moal
Michel
M
Piazza
Pier-Vincenzo
PV
Abrous
Djoher Nora
DN
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000089622:Doublecortin Domain Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D011500:Protein Synthesis Inhibitors; D008746:Methylazoxymethanol Acetate; D001973:Bromodeoxyuridine