Alzheimer’s disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats’ response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD.

Recently, our research team has reported that Tualang honey was able to improve immediate memory in postmenopausal women comparable with that of estrogen progestin therapy. Therefore the aim of the present study was to examine the effects of Tualang honey supplement on hippocampal morphology and memory performance in ovariectomized (OVX) rats exposed to social instability stress. Female Sprague-Dawley rats were divided into six groups: (i) sham-operated controls, (ii) stressed sham-operated controls, (iii) OVX rats, (iv) stressed OVX rats, (v) stressed OVX rats treated with 17β-estradiol (E2), and (vi) stressed OVX rats treated with Tualang honey. These rats were subjected to social instability stress procedure followed by novel object recognition (NOR) test. Right brain hemispheres were subjected to Nissl staining. The number and arrangement of pyramidal neurons in regions of CA1, CA2, CA3 and the dentate gyrus (DG) were recorded. Two-way ANOVA analyses showed significant interactions between stress and OVX in both STM and LTM test as well as number of Nissl-positive cells in all hippocampal regions. Both E2 and Tualang honey treatments improved both short-term and long-term memory and enhanced the neuronal proliferation of hippocampal CA2, CA3 and DG regions compared to that of untreated stressed OVX rats.

A possible interaction between glucocorticoids and estrogen-induced increases in brain-derived-neurotrophic factor (BDNF) expression in enhancing depressive-like behaviour has been documented. Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17β-estradiol (E2) on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX) rats. The animals were divided into six groups: (i) nonstressed sham-operated control, (ii) stressed sham-operated control, (iii) nonstressed OVX, (iv) stressed OVX, (v) stressed OVX treated with E2 (20 μg daily, sc), and (vi) stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally). Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH) and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration was significantly decreased compared to other experimental groups. These changes were notably reversed by both E2 and Tualang honey. In conclusion, both Tualang honey and E2 mediate antidepressive-like effects in stressed OVX rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis and enhancement of the BDNF concentration.

The present study aims to evaluate the antioxidant and anxiolytic-like effect of Tualang honey in stressed ovariectomized (OVX) rats. The animals were divided into; (i) nonstressed sham-operated control rats, (ii) sham-operated control rats exposed to stress, (iii) nonstressed OVX rats, (iv) OVX rats exposed to stress, (v) OVX rats exposed to stress and treated with 17 β-oestradiol (E2) (20 μg daily, sc), and (vi) OVX rats exposed to stress and treated with Tualang honey (0.2 g/kg body weight, orally). The open field test was used to evaluate the anxiety-like behaviour and ELISA kits were used to measure oxidant/antioxidant status of the brain homogenates. The result showed that anxiety-like behavior was significantly increased in stressed OVX compared to other groups, and administering either E2 or Tualang honey significantly decreased anxiety-like behaviour in stressed OVX rats. The levels of malondialdehyde (MDA) and protein carbonyl (PCO) were significantly decreased while the levels/activities of superoxide dismutase (SOD), glutathione S-transferases (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly increased in the brain homogenates of treated stressed OVX groups compared to untreated stressed OVX. In conclusion, Tualang honey has protective effects against brain oxidative stress and may be useful alternative anxiolytic agent especially for postmenopausal women.

Recent evidence has exhibited dietary influence on the manifestation of different types of behavior induced by stressor tasks. The present study examined the effects of Tualang honey supplement administered with the goal of preventing or attenuating the occurrence of stress-related behaviors in male rats subjected to noise stress. Forty-eight adult male rats were randomly divided into the following four groups: i) nonstressed with vehicle, ii) nonstressed with Tualang honey, iii) stressed with vehicle, and iv) stressed with honey. The supplement was given once daily via oral gavage at 0.2 g/kg body weight. Two types of behavioral tests were performed, namely, the novel object recognition test to evaluate working memory and the forced swimming test to evaluate depressive-like behavior. Data were analyzed by a two-way analysis of variance (ANOVA) using IBM SPSS 18.0. It was observed that the rats subjected to noise stress expressed higher levels of depressive-like behavior and lower memory functions compared to the unexposed control rats. In addition, our results indicated that the supplementation regimen successfully counteracted the effects of noise stress. The forced swimming test indicated that climbing and swimming times were significantly increased and immobility times significantly decreased in honey-supplemented rats, thereby demonstrating an antidepressant-like effect. Furthermore, cognitive function was shown to be intensely affected by noise stress, but the effects were counteracted by the honey supplement. These findings suggest that subchronic exposure to noise stress induces depressive-like behavior and reduces cognitive functions, and that these effects can be attenuated by Tualang honey supplementation. This warrants further studies to examine the role of Tulang honey in mediating such effects.

The composition and physicochemical properties of honey are variable depending on its floral source and often named according to the geographical location. The potential medicinal benefits of Tualang honey, a multifloral jungle honey found in Malaysia, have recently been attracting attention because of its reported beneficial effects in various diseases. This paper reviews the effects of honey, particularly Tualang honey, on learning and memory. Information regarding the effects of Tualang honey on learning and memory in human as well as animal models is gleaned to hypothesize its underlying mechanisms. These studies show that Tualang honey improves morphology of memory-related brain areas, reduces brain oxidative stress, increases brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) concentrations, and reduces acetylcholinesterase (AChE) in the brain homogenates. Its anti-inflammatory roles in reducing inflammatory trigger and microglial activation have yet to be investigated. It is hypothesized that the improvement in learning and memory following Tualang honey supplementation is due to the significant improvement in brain morphology and enhancement of brain cholinergic system secondary to reduction in brain oxidative damage and/or upregulation of BDNF concentration. Further studies are imperative to elucidate the molecular mechanism of actions.

This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups, (n = 10 per group). These were non-stressed sham-operated control rats, stressed sham-operated control rats, non-stressed OVX rats, and stressed OVX rats. The rats were subjected to social instability stress procedure for 15 days. Novel object recognition, open field, and forced swim tests were conducted after the stress procedure. Serum estradiol, ACTH and corticosterone levels were measured using commercially available ELISA kits. Lower serum estradiol level and uterine weight with higher weight gain were observed in OVX rats compared to sham-operated controls. Serum ACTH, and corticosterone levels were higher in stressed compared to non-stressed groups. Memory deficit and anxiety- and depressive-like behaviour were significantly increased in stressed compared to non-stressed OVX rats but these changes were not seen in sham-operated controls. These results suggest that the high circulating corticosterone acts synergistically with low circulating estradiol to exert negative effects on mood and memory function.

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