Effects of isoflavones on behavior, estradiol, glutamate, and GABA levels in intact middle-aged female rats.

OBJECTIVES: Estrogen and phytoestrogens, mainly isoflavones (SIF) treatment has been suggested to improve mood, behavior, and cognitive function in postmenopausal women. However, there is a lack of information on the mechanism of such treatment on the central nervous system. We used rats to investigate the effects of long-term treatment with commercial isoflavones on behavior, hormones, and brain neurotransmitter levels.

METHODS: Intact female middle-aged (12 months) rats received 50, 100, and 200 mg/kg/day of commercial isoflavones extract by gavage for 90 days. After treatment, locomotor activity, anxiety-like behavior, spatial memory, estradiol, and neurotransmitter levels were measured.

RESULTS: Isoflavones treatment decreased total body weight gain in rats received 100 (P < 0.05) and 200 mg/kg (P < 0.05). There were no differences in locomotor activity or anxiety-like behavior; however, isoflavone treatment improved spatial memory (P < 0.05). Estradiol concentration was increased (P < 0.05) in groups SIF 100 and SIF 200. Glutamate (P < 0.01) and γ-aminobutyric acid (GABA) were increased in the prefrontal cortex (PFC) of rats receiving the highest doses and in the hypothalamus in rats that received SIF200 (P < 0.05).

DISCUSSION: These findings showed that long-term treatment with commercial isoflavones decreased total body weight gain and facilitated spatial memory performance in rats and this may be involved with the increase in estradiol levels as well as the increase in GABA and glutamate levels in PFC. Furthermore, isoflavones treatment may attenuate age-related cognitive impairment and may therefore be an effective tool to combat this undesirable feature of the natural aging process.