Minocycline prevents Aβ(25–35)-induced reduction of somatostatin and neprilysin content in rat temporal cortex

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Aims Tetracyclines have been demonstrated to inhibit formation of β-amyloid (Aβ) aggregates and to disassemble preformed fibrils. Minocycline, a semi-synthetic second-generation tetracycline, can reverse Aβ-induced impairment of cognitive functions. Since somatostatin is involved in cognition and we recently showed that Aβ(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 Aβ(25–35)-infused and healthy rats. Moreover, since brain levels of neprilysin, an Aβ-degrading enzyme, decrease with age, favoring the appearance of senile neuritic plaques, we tested whether minocyline could affect neprilysin expression. Main methods Wistar rats were thus injected with minocycline twice on the first day of treatment. On the following day, and during 14 days, Aβ(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. Key findings Minocycline abrogated the Aβ(25–35)-induced decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-CREB content and neprilysin levels. Minocycline alone enhanced these targets. Significance Our findings indicate that minocycline prevents the deleterious effects of Aβ(25–35) on SRIF and neprilysin expression in the rat temporal cortex and that it has protective effects per se on these parameters.