8-[2-(2-Pentyl-Cyclopropylmethyl)-Cyclopropyl]-Octanoic Acid and Its Diastereomers Improve Age-Related Cognitive Deterioration
2012
Kanno, Takeshi | Yaguchi, Takahiro | Shimizu, Tadashi | Tanaka, Akito | Nishizaki, Tomoyuki
Racemic 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a linoleic acid derivative with cyclopropane rings instead of cis-double bonds, contains possible four diastereomers such as α,α-, α,β-, β,α-, and β,β-DCP-LA. The present study examined the effect of racemic and diastereomeric DCP-LA on age-related learning and memory disorders using accelerated-senescence-prone mice 8 (SAMP8) and accelerated-senescence-resistant mice 1 (SAMR1). In the water maze test, the acquisition and retention latencies for SAMP8 mice were significantly longer than the latency for SAMR1 mice, indicating spatial learning and memory impairment for SAMP8 mice. All the racemic (1 mg/kg, per os) and diastereomeric DCP-LA (0.25 mg/kg, per os) significantly shortened the acquisition latency for SAMP8 mice, and racemic, α,α- and α,β-DCP-LA significantly shortened the retention latency, with the advantage greater than the acetylcholine (ACh) esterase inhibitor galanthamine. The results of the present study show that all the racemic and diastereomeric DCP-LA, has the potential to improve age-related learning and memory deterioration, the potential varying among them.
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