Minocycline prevents Abeta(25-35)-induced reduction of somatostatin and neprilysin content in rat temporal cortex.
OBJECTIVE
Tetracyclines have been demonstrated to inhibit formation of beta-amyloid (Abeta) aggregates and to disassemble preformed fibrils. Minocycline, a semi-synthetic second-generation tetracycline, can reverse Abeta-induced impairment of cognitive functions. Since somatostatin is involved in cognition and we recently showed that Abeta(25-35) lowers somatostatin expression in the rat temporal cortex, our aim here was to analyze the effects of minocycline on somatostatin immunoreactivity and mRNA levels in the temporal cortex of Abeta(25-35)-infused and healthy rats. Moreover, since brain levels of neprilysin, an Abeta-degrading enzyme, decrease with age, favoring the appearance of senile neuritic plaques, we tested whether minocyline could affect neprilysin expression.


METHODS
Wistar rats were thus injected with minocycline twice on the first day of treatment. On the following day, and during 14 days, Abeta(25-35) or vehicle were administered. Minocycline was injected once again on days 13 and 14. All animals were sacrificed 24 h after the last drug injection.


RESULTS
Minocycline abrogated the Abeta(25-35)-induced decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-CREB content and neprilysin levels. Minocycline alone enhanced these targets.


CONCLUSIONS
Our findings indicate that minocycline prevents the deleterious effects of Abeta(25-35) on SRIF and neprilysin expression in the rat temporal cortex and that it has protective effects per se on these parameters.
Burgos-Ramos
E
E
Departamento de Endocrinología, Hospital Universitario Infantil Niño Jesús, Spain.
Puebla-Jiménez
L
L
Arilla-Ferreiro
E
E
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D015260:Neprilysin / Q000032:analysis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000032:analysis* / Q000235:genetics; D013702:Temporal Lobe / Q000737:chemistry / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D000900:Anti-Bacterial Agents; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D013004:Somatostatin; D015260:Neprilysin; D008911:Minocycline