Underlying mechanisms behind the neuroprotective effect of vanillic acid against diabetes-associated cognitive decline: An in vivo study in a rat model.

Hippocampal synaptic dysfunction, oxidative stress, neuroinflammation, and neuronal loss play critical roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The study aimed to investigate the effects of vanillic acid (VA), a phenolic compound, against DACD and explore the potential underlying mechanisms. Following confirmation of diabetes, rats were treated with VA (50 mg/kg/day; P.O.) or insulin (6 IU/rat/day; S.C.) for 8 consecutive weeks. The cognitive performance of the rats was evaluated using passive-avoidance and water-maze tasks. Long-term potentiation (LTP) was induced at hippocampal dentate gyrus (DG) synapses in response to high-frequency stimulation (HFS) applied to the perforant pathway (PP) to evaluate synaptic plasticity. Oxidative stress factors, inflammatory markers, and histological changes were evaluated in the rat hippocampus. This study showed that streptozotocin (STZ)-induced diabetes caused cognitive decline that was associated with inhibition of LTP induction, suppression of enzymatic antioxidant activities, enhanced lipid peroxidation, elevated levels of inflammatory proteins, and neuronal loss. Interestingly, chronic treatment with VA alleviated blood glucose levels, improved cognitive decline, ameliorated LTP impairment, modulated oxidative-antioxidative status, inhibited inflammatory response, and prevented neuronal loss in diabetic rats at a level comparable to insulin therapy. The results suggest that the antihyperglycemic, antioxidative, anti-inflammatory, and neuroplastic properties of VA may be the mechanisms behind its neuroprotective effect against DACD.

Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention.

Aims: This study was designed to investigate the effects of resistance training (RT) and hawthorn extract (Ha) on Glypican-4 (GPC-4) and Insulin-regulated glycosylphosphatidylinositol-specific phospholipase D (GPLD1) serum levels in T2DM and to examine the relationship of these variables with glycemic indexes. Method: 40 male Wistar rats were divided into five equal groups: Healthy Control (H-C), Diabetes Control (D-C), Diabetes Resistance training (D-RT), Diabetes Hawthorn (D-Ha), and Diabetes Resistance training Hawthorn (D-RT-Ha). T2DM was induced with a 4-week high-fat diet (HFD) and one dose of STZ intraperitoneal injection (35 mg/kg). 1-week after the injection, RT (with a range of 50%-100%1RM/3 day/week) and gavage of Ha extract (100 mg/kg/day) was performed for 12 weeks. Results: The glycemic indices improvement (reducing blood glucose and increasing serum insulin level) caused by RT and/or Ha increased GPC-4 and decreased GPLD1 in the T2DM rats, but these positive changes were more effective in the combination of RT + Ha. A strong correlation was also observed between GPC-4 and GPLD1 with blood glucose and insulin. Conclusion: The increase in serum GPC-4 levels was probably due to the direct effect of RT + Ha, and the improvement of glycemic indexes after RT and Ha. The double effect of RT + Ha can be a regulatory mechanism for GPC-4 and its related factors in controlling T2DM complications.

The effects of polyvinyl alcohol-coated selenium nanoparticles on memory impairment in rats.

Some mineral elements exert beneficial neuroprotection, especially in the form of nanoparticles. The aim of the present study was to evaluate the effects of selenium nanoparticles (SeNPs) and polyvinyl alcohol (PVA)-coated SeNPs (PVA-SeNPs) on Alzheimer's disease (AD) in a rat model of AD. Twenty-eight rats were randomly divided into four groups of seven rats: control, Alz, Alz + Se, and Alz + Se-PV groups. PVA-SeNPs and SeNPs were chemically synthesized and orally administrated (0.4 mg/kg) to the AD rats for one month. AD was induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ). The memory function was assessed by the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The expression of hippocampal brain-derived neurotrophic factor (BDNF) and stress oxidative markers (MDA and TAC), and the number of amyloid-beta (Aß) plaques were assessed using ELISA kits, biochemical methods, and Congo red staining, respectively. The results of the behavioral tests showed that the discrimination index in the NOR test increased in the Alz + PVA-SeNPs group compared to the Alz group. Memory performance in the PAL task improved in the PVA-SeNPs and SeNPs groups compared to the Alz group. The level of the BDNF in both of the Alz treatment groups (PVA-SeNPs and SeNPs) showed a significant increase compared to the Alz group. MDA levels and Aß plaques decreased in both NPs-treated Alz groups, while TAC levels decreased in all Alz groups. PVA-SeNPs were more effective than SeNPs in the improvement of the cognition deficit. The results suggest that PVA-SeNPs improve the cognition and memory deficit induced by an ICV injection of STZ through a decrease in the number of Aß plaques and malondialdehyde levels and an increase in the BDNF levels.

Chitosan-coated Selenium nanoparticles enhance the efficiency of stem cells in the neuroprotection of streptozotocin-induced neurotoxicity in male rats.

Alzheimer's disease (AD) is one of the common neurodegenerative diseases characterized by memory impairment. The protective effects of stem cell-based therapy have been reported in AD. In this study, it was assumed that Chitosan-coated Selenium nanoparticles (ChSeNPs) increase the efficiency of stem cells in the attenuation of neurotoxicity in the rat AD model. The AD model was induced using Streptozotocin (STZ) and treated by the adipose-derived mesenchymal stem cells (AMSCs) and SeNPs/ChSeNPs (0.4 mg/kg). Passive avoidance learning and recognition memory were assessed using shuttle box and novel object recognition tasks. The amyloid-beta deposition, the injected cells' homing and survival, antioxidant capacity, and BDNF concentration were evaluated using the histological, biochemical, and ELISA methods. The results showed that the combined administration of ChSeNPs and AMSCs is more effective in increasing the step-through latency and discrimination index than administering SeNPs and stem cells. Combined therapy caused a significant increase in antioxidant capacity that ChSeNPs was more effective than SeNPs, while AMSCs beside SeNPs had a greater effect on BDNF levels compared to conventional treatment of nanoparticles or AMSCs alone. Ultimately, the homing and survival of the transplanted AMSCs were greater in the group that received both stem cells and ChSeNPs. Taken together, it seems that the administration of ChSeNPs enhances the efficiency of transplanted stem cells in decreasing the neurotoxicity induced by STZ through an increase in the antioxidant capacity.

Administration of Selenium Nanoparticles Reverses Streptozotocin-Induced Neurotoxicity in the male rats.

Alzheimer's disease is the most common neurodegenerative disease associated with deposition of amyloid-beta and the increased oxidative stress. High free radical scavenging ability of selenium nanoparticles (SeNPs) has been acknowledged, so in the present study, the effects of treatment with SeNPs on Streptozotocin (STZ)-induced neurotoxicity were evaluated in the male rats. Learning and memory impairment was induced by intraventricular injection of STZ. Following induction of memory impairment, the rats received 0.4 mg/kg of SeNPs daily for one month. Memory function, antioxidant capacity, and deposition of Amyloid ß (Aß) were assessed using the shuttle box task, biochemical methods, and Congo red staining. Injection of STZ caused memory impairment, a decrease in the level of total thiol group (TTG), and an increase in the malondialdehyde (MDA) content and deposition of Aß. Administration of SeNPs reversed the neurotoxicity induced by STZ. It seems that SeNPs likely had neuroprotective effects on the animal model of Alzheimer's disease through increasing antioxidants҆ capacity.

Synergistic effects of adipose-derived mesenchymal stem cells and selenium nanoparticles on streptozotocin-induced memory impairment in the rat.

AIMS: Memory impairment is determined to be the most well-known symptom of Alzheimer's disease (AD). Although cell therapy seems is an efficient therapeutic strategy to attenuate the AD-related memory impairment, transplanted cells have a short lifespan and do not survive long term in the recipient animals. Herein, we investigated whether the combination therapy of Selenium nanoparticles (SeNPs) and stem cells attenuates the neurotoxicity in an AD animal model. MATERIAL AND METHODS: The adipose-derived mesenchymal stem cells (AMSCs) were transplanted in the AD model. In addition to cell injections, the animals also received oral administration of SeNPs (0.4 mg/kg) for one month. Recognition memory, cell survival, and BDNF concentration were assessed using the novel object recognition task, immunofluorescence, and ELISA methods. KEY FINDINGS: Our results showed that the combined therapy was more effective in increasing the discrimination index than the administering SeNPs or AMSCs alone. Moreover, SeNPs and stem cells together had the greatest effects in reducing the deposition of Aß and increasing the concentration of BDNF. Ultimately, the survival and proliferation of transplanted cells were more in the group that received stem cells besides SeNPs. SIGNIFICANCE: Taken together, it seems that the transplantation of MSCs combined with SeNPs could achieve better results in the neuroprotection in the AD model than a conventional treatment of SeNPs or stem cells alone.

Coenzyme Q10 supplementation reverses diabetes-related impairments in long-term potentiation induction in hippocampal dentate gyrus granular cells: An in vivo study.

Diabetes mellitus (DM) is associated with impaired hippocampal synaptic plasticity. Coenzyme Q10 (CoQ10) acts as an antioxidant and exerts neuroprotective effects. Accordingly, this study aimed at evaluating the effects of CoQ10 on hippocampal long-term potentiation (LTP) and paired-pulse facilitation (PPF) in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were randomly divided into six groups (n = 8 per group) as follows and treated for 90 days: the control, control + low dose of CoQ10 (100 mg/kg), control + high dose of CoQ10 (600 mg/kg), diabetic, diabetic + low dose of CoQ10, and diabetic + high dose of CoQ10 groups. Diabetes was induced by a single intraperitoneal injection of 50 mg/kg STZ. The population spike (PS) amplitude and slope of excitatory post synaptic potentials (EPSPs) were measured in dentate gyrus (DG) area in response to the stimulation applied to the perforant path (PP). The results showed that the STZ-induced diabetes impaired LTP induction in the PP-DG synapses. This finding is supported by the decreased EPSP slope and PS amplitude of LTP (P < 0.05). Both low- and high-dose CoQ10 supplementation in the control and diabetic animals enhanced EPSP slope and PS amplitude of LTP in the granular cells of DG (P < 0.05). PPF was affected by LTP induction in diabetic animals receiving the high dose of CoQ10 (P < 0.05). It is suggested that CoQ10 administration could attenuate deteriorative effect of STZ-induced diabetes on in vivo LTP in the DG. The enhanced transmitter release can be partly one of the possible underlying mechanism(s) responsible for the LTP induction in the diabetic animals treated with CoQ10.

Intracerebroventricular microinjection of kaempferol on memory retention of passive avoidance learning in rats: involvement of cholinergic mechanism(s).

Purpose of the study: Kaempferol (KM) is a flavonoid found in plant-derived foods and medicinal plants. Recently, it is well established that KM plays a protective role to develop Alzheimer's disease. The current study aimed at evaluating the effect of intracerebroventricular micro-injection of KM on memory retention of passive avoidance learning (MRPAM) and identifying the potentially related cholinergic mechanisms (ChMs) in rats. Materials and methods: In the current study, male Wistar rats randomly divided into control, vehicle and KM (10, 20 and 40 µg/rat) groups. Moreover, MRPAM was evaluated by shuttle box test. The role of ChM was studied using non-selective and selective acetylcholine antagonists (scopolamine [SCN], 4-DAMP and methoctramine [MN], respectively) as well as pirenzepine (PZ) in combination with KM. Results: The employment of KM (40 µg/rat) improved the SCN-induced memory impairment in MRPAM. Co-treatment with KM (40 µg/rat) plus 4-DAMP significantly increased the step-through latency (STL, P < 0.05; 167 ± 28 s) and decreased the total dark chamber (TDC, P < 0.05; 121 ± 31 s) compared with those of the 4-DAMP group (STL: 75 ± 13 s; TDC: 178 ± 46 s). Co-treatment with KM (40 µg/rat) plus PZ attenuated STL, and also increased TDC (P < 0.01; 220 ± 28 s) compared with those of the PZ group. Co-treatment with KM (10 and 20 µg/rat) and MN increased STL (P < 0.05), and deceased TDC compared with those of the MN group (P < 0.01). Conclusions: Totally, the results of the present study showed that cholinergic system may be involved in improving effect of KM on SCN-induced memory impairment.

Effect of coenzyme Q10 supplementation on diabetes induced memory deficits in rats.

The main objective of current work was to determine the effects of low and high dose supplementation with coenzyme Q10 (CoQ10) on spatial learning and memory in rats with streptozotocin (STZ)-induced diabetes. Male Wistar rats (weighing 220 ± 10) were randomly divided into six groups: (i) Control (Con, n = 8); (ii) Control+ Low dose of CoQ10 (100 mg/kg) (CLD, n = 10); (iii) Control+ high dose of CoQ10 (600 mg/kg) (CHD, n = 10); (iv) Diabetic (D, n = 10); (v) Diabetic + Low dose of CoQ10 (100 mg/kg) (DLD, n = 10); (vi) Diabetic + high dose of CoQ10 (600 mg/kg) (DHD, n = 10). Diabetes was induced by a single intraperitoneal injection of 50 mg/kg STZ. CoQ10 was administered intragastrically by gavage once a day for 90 days. After 90 days, Morris water maze (MWM) task was used to evaluate the spatial learning and memory in rats. Diabetic animals showed a slower rate of acquisition with respect to the control animals [F (1, 51) = 92.81, P < 0.0001, two-way ANOVA]. High dose (but no low dose) supplementation with CoQ10 could attenuate deteriorative effect of diabetes on memory acquisition. Diabetic animals which received CoQ10 (600 mg/kg) show a considerable decrease in escape latency and traveled distance compared to diabetic animals (p < 0.05, two-way ANOVA,). The present study has shown that low dose supplementation with CoQ10 in diabetic rats failed to improve deficits in cognitive function but high dose supplementation with CoQ10 reversed diabetes-related declines in spatial learning.

Investigation of protective effects of coenzyme Q10 on impaired synaptic plasticity in a male rat model of Alzheimer's disease.

Oxidative stress plays a key role in contributing to ß-amyloid (Aß) deposition in Alzheimer's disease (AD). Coenzyme Q10 (Q10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals. In this study, we investigated the neuroprotective effects of Q10 on Aß-induced impairment in hippocampal long-term potentiation (LTP), a widely researched model of synaptic plasticity, which occurs during learning and memory, in a rat model of AD. In this study, 50 adult male Wistar rats were assigned to five groups: control group (saline); sham group; intraventricular PBS injection, Aß group; intraventricular Aß injection, Q10 group; and Q10 via oral gavage and Q10 + Aß group. Q10 was administered via oral gavage, once a day, for 3 weeks before and 3 weeks after the Aß injection. After the treatment period, in vivo electrophysiological recordings were performed to quantify the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the hippocampal dentate gyrus. LTP was created by a high-frequency stimulation of the perforant pathway. Following LTP induction, the EPSP slope and PS amplitude were significantly diminished in Aß-injected rats, compared with sham and control rats. Q10 treatment of Aß-injected rats significantly attenuated these decreases, suggesting that Q10 reduces the effects of Aß on LTP. Aß significantly increased serum malondialdehyde levels and total oxidant levels, whereas Q10 supplementation significantly reversed these parameters and increased total antioxidant capacity levels. The present findings suggested that Q10 treatment offers neuroprotection against the detrimental effects of Aß on hippocampal synaptic plasticity via its antioxidant activity.

Influence of Chronic Coenzyme Q10 Supplementation on Cognitive Function, Learning, and Memory in Healthy and Diabetic Middle-Aged Rats.

Diabetes mellitus can induce impairment in learning and memory. Cognitive and memory deficits are common in older adults and especially in those with diabetes. This is mainly because of hyperglycemia, oxidative stress, and vascular abnormalities. Coenzyme Q10 (CoQ10) can decrease oxidative stress, hyperglycemia, and inflammatory markers, and improve vascular function. Therefore, the aim of the present study was to investigate the possible effects of CoQ10 on cognitive function, learning, and memory in middle-aged healthy and diabetic rats. Adult middle-aged male Wistar rats (390-460 g, 12-13 months old) were divided into 6 experimental groups. Diabetes was induced by a single i.p. injection of streptozotocin (60 mg/kg). CoQ10 (20 or 120 mg/kg, orally by gavage) was administered for 45 days. The cognitive function and learning memory of rats were evaluated using novel object recognition (NOR) and passive avoidance tests. The discrimination index of the NOR test in the diabetic groups receiving CoQ10 (20 or 120 mg/kg) and the healthy group receiving CoQ10 (120 mg/kg) was significantly higher than that in the control group. In addition, the step through latency was significantly longer and the time spent in the dark compartment was significantly shorter in the diabetic groups receiving CoQ10 than in the control group. CoQ10 supplementation can improve learning and memory deficits induced by diabetes in older subjects. In addition, CoQ10 at higher doses can improve cognitive performance in older healthy subjects.

Effects of the hydroalcoholic extract of Rosa damascena on learning and memory in male rats consuming a high-fat diet.

CONTEXT: High-fat diet (HFD) can cause deficits in learning and memory through oxidative stress and increase Alzheimer disease risk. Rosa damascena Mill. (Rosaceae) extract possesses potent antioxidant properties. OBJECTIVE: This study investigated the effects of the hydroalcoholic extracts of petals of R. damascena on learning and memory in male rats consuming an HFD. MATERIALS AND METHODS: Forty male Wistar rats (200-250 g) were randomly assigned to four groups: control, R. damascena extract, HFD and HFD + extract. The extract (1 g/kg bw daily) was administered by oral gavage for 1 month. Animals were allowed free access to high-fat chow for 3 months. The Morris water maze and the passive avoidance learning tests were used to assess learning and memory. RESULTS: In the passive avoidance learning test, the step-through latencies in the retention test (STLr) of the extract (147.4 ± 23.3) and HFD (150.3 ± 25.2) groups were significantly lower than those of the control group (270.4 ± 10.5) (respectively, p < 0.001 and p < 0.01). STLr was significantly higher in the HFD + extract group (265.3 ± 10.6) than in the HFD group (150.3 ± 25.2) (p < 0.01). Time spent in the dark compartment (TDC) in the HFD + extract group (5.3 ± 2.6) was significantly lower than that in the HFD group (85.8 ± 19.1) (p < 0.05). DISCUSSION AND CONCLUSION: Our results indicate that, while HFD or R. damascena extract alone leads to memory deficits, R. damascena extract exerted a positive effect on HFD-induced memory deficits. We hypothesize that the observed effects of R. damascena extract are likely due to its strong antioxidant properties.

Effects of Hypericum Scabrum extract on anxiety and oxidative stress biomarkers in rats fed a long-term high-fat diet.

The continuous and long-term consumption of a high-fat diet (HFD) leads to weight gain and obesity. A HFD and obesity increase the risks of psychiatric disorders, such as anxiety and depression. In this study, we investigated the effects of a Hypericum Scabrum (H. scabrum) extract, which is an antioxidant, on anxiety in rats fed a long-term HFD. Sixty male Wistar rats were divided into the following six groups: (1) Control (standard diet), (2) Ext100 [standard diet supplemented with extract (100 mg/kg once/day)], (3) Ext300 [standard diet supplemented with extract (300 mg/kg once/day)], (4) HFD, (HFD), (5) HFD + Ext100, and (6) HFD + Ext300. The groups were fed their diet for 3 months. Anxiety was measured with the elevated plus-maze test. At the end of the study, blood samples were taken, and biochemical parameters and oxidative stress biomarker levels were determined in the plasma. Compared to the control group, the HFD group exhibited significant decreases in both the time in the open arms and number of entries into the open arms. H. scabrum extract supplementation significantly increased these parameters in the HFD-fed groups. The HFD significantly increased serum malondialdehyde levels and significantly decreased total glutathione levels, while H. scabrum extract supplementation significantly reversed these parameters. In conclusion, these results showed that a HFD increased anxiety behavior. In contrast, H. scabrum extract supplementation had anxiolytic effects and reversed the effects of the HFD, which suggested that the effects of H. scabrum extract supplementation were due to its strong antioxidant properties.

Study of the effect of extract of Thymus vulgaris on anxiety in male rats.

There is some evidence in traditional medicine for the effectiveness of Thymus vulgaris ( bǎi lǐ xiang) in the treatment of anxiety in humans. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of extract of T. vulgaris on rat behavior in the EPM. In the present study, the data were obtained from male Wistar rats. Animals were divided into four groups: saline group and T. vulgaris groups (50 mg/kg, 100 mg/kg, and 200 mg/kg infusion for 7 days by feeding). During the test period, the total distance covered by animals, the number of open- and closed-arm entries, and the time spent in open and closed arms of the EPM were recorded. T. vulgaris increased open-arm exploration and open-arm entry in the EPM, whereas extract of this plant has no effects on the total distance covered by animals and the number of closed-arm entries. The results of the present experiment indicate that T. vulgaris may have an anxiolytic profile in rat behavior in the EPM test, which is not influenced by the locomotor activity. Further research is required to determine the mechanisms by which T. vulgaris extract exerts an anxiolytic effect in rats.

The treatment combination of vitamins E and C and astaxanthin prevents high-fat diet induced memory deficits in rats.

Cognitive function is impaired by imbalanced diet consumption. High-fat diet (HFD) induces oxidative stress and metabolic disorders, which results in neuronal damage and interferes with synaptic transmission and neurogenesis; hence, a decline in learning and memory. Antioxidants are believed to have positive effects on cognitive function. The objective of this study was to determine the relation between the chronic consumption of a HFD and antioxidants on passive avoidance learning (PAL) in male rats. Wistar rats were randomly assigned into the following five groups (N=6-8): Control group-consumed an ordinary diet; HFD group-received high-fat diets only; ANO group-received HFD plus antioxidants (vitamins C and E and astaxanthin (ASX)); RHFD group-received the restricted HFD (30% less than the HFD group); and RANO group-received restricted HFD plus antioxidants (30% less than the ANO group). Following 6months of controlled dietary condition as mentioned above, in each experimental group, the PAL was assessed using shuttle box apparatus. Our results showed that HFD caused a decrease in step through latency in the retention test (STLr) and increased the time spent in the dark compartment in the retention test (TDC) when compared to the control group. Antioxidant supplementation caused an increase in STLr and decrease in TDC when compared to the control group. Furthermore, RHFD and RANO had no significant effect on STLr and TDC compared with the control group. According to our results, HFD impairs PAL and the combination of vitamins C and E and astaxanthin improves PAL deficits in the HFD group.

The protective effect of Borago Officinalis extract on amyloid ß (25-35)-induced long term potentiation disruption in the dentate gyrus of male rats.

Alzheimer's disease (AD) begins with impairment in synaptic functions before developing into later neurodegeneration and neural loss. In the present study we have examined the protective effects of Borago Officinalis (borage) extract on amyloid ß (Aß)--Induced long term potentiation (LTP) disruption in hippocampal dentate gyrus (DG). Wistar male rats received intrahippocampal (IHP) injection of the Aß (25-35) and borage extract throughout gestation (100 mg/kg). LTP in perforant path- DG synapses was assessed using electrophysiology method and field excitatory post- synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured by 400 Hz tetanization. Finally, the total thiol content of hippocampus was measured using colorimetric reaction based on the Ellman's method. The results showed that Aß (25-35) significantly decreased fEPSP slope and SP amplitude comparing with the control and sham group, whereas borage extract administration increased these parameters compared to the Aß group. Aß induced a remarkable decrease in total thiol content of hippocampus and borage prevented the decrease of the hippocampal total sulfhydryl (SH) groups. This data suggest that Aß (25-35) can effectively inhibit LTP in the granular cells of the DG in hippocampus, and borage supplementation reverse the synaptic plasticity in DG following Aß treatment and that borage consumption may lead to an improvement of AD-induced cognitive dysfunction.

Protective effects of Borago officinalis extract on amyloid ß-peptide(25-35)-induced memory impairment in male rats: a behavioral study.

Alzheimer's disease (AD) is a neurodegenerative disorder and most common form of dementia that leads to memory impairment. In the present study we have examined the protective effects of Borago officinalis (borage) extract on Amyloid ß (A ß)-Induced memory impairment. Wistar male rats received intrahippocampal (IHP) injection of the A ß (25-35) and borage extract throughout gestation (100 mg/kg). Learning and memory functions in the rats were examined by the passive avoidance and the Morris water maze (MWM) tasks. Finally, the antioxidant capacity of hippocampus was measured using ferric ion reducing antioxidant power (FRAP) assay. The results showed that A ß (25-35) impaired step-through latency and time in dark compartment in passive avoidance task. In the MWM, A ß (25-35) significantly increased escape latency and traveled distance. Borage administration attenuated the A ß-induced memory impairment in both the passive avoidance and the MWM tasks. A ß induced a remarkable decrease in antioxidant power (FRAP value) of hippocampus and borage prevented the decrease of the hippocampal antioxidant status. This data suggests that borage could improve the learning impairment and oxidative damage in the hippocampal tissue following A ß treatment and that borage consumption may lead to an improvement of AD-induced cognitive dysfunction.

Preventive effect of Teucrium polium on learning and memory deficits in diabetic rats.

BACKGROUND: Cognitive impairment occurs in diabetes mellitus. Teucrium polium L. (Lamiaceae) has been used in folk medicine to improve mental performance. Here we hypothesized that chronic treatment with an aqueous extract of Teucrium polium (100, 200 and 400 mg/kg, p.o.) would have an effect on passive avoidance learning (PAL) and memory in control and streptozocin-induced diabetic rats. MATERIAL/METHODS: Treatments were begun at the onset of hyperglycemia, and PAL was assessed 30 days later. A retention test was performed 24 h (hours) after training. After PAL and memory assessment, animals were weighed and blood samples were drawn for plasma glucose measurement. RESULTS: Diabetes caused impairment in acquisition of PAL and retrieval of memory. Teucrium polium treatment (200 and 400 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. The 100 mg/kg dose did not affect cognitive function. Teucrium polium treatment partially improved the reduced body weight and hyperglycemia of treated diabetic rats, although the differences were not significant compared to non-treated diabetic rats. CONCLUSIONS: These results show that Teucrium polium prevented the deleterious effects of diabetes on PAL and memory. Antioxidant, anticholinesterase and hypoglycemic effects of Teucrium may be involved in the obtained effects. Therefore, Teucrium polium appears to be a promising candidate for memory improvement in diabetes, but this needs confirmation by future clinical studies.

Effects of Hypericum perforatum extract on diabetes-induced learning and memory impairment in rats.

Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin-induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients.

Ascorbic acid supplementation could affect passive avoidance learning and memory in rat.

Ascorbic acid (vitamin C) is required for health and, in particular, its supplementation has beneficial effects in some pathological conditions. There are conflicting reports regarding the usefulness of ascorbic acid in the treatment of dementia. In this study, we investigated the effects of acute, short- and long-term pre-training administration of ascorbic acid (60,120 mg/kg) on passive avoidance learning (PAL) and memory in rats. Retention test was done 24h after training. The results showed that acute injection of ascorbic acid had no significant effect on PAL. On the other hand, both in the short- and long-term ascorbic acid treated groups trials to acquisition were less than control group. Also, ascorbic acid prolonged the step-through latency (STL) and decreased the time spent in the dark compartment in retention test. Thus, it can be concluded that short- and long-term supplementation with ascorbic acid has facilitatory effects on acquisition and retrieval processes of passive avoidance learning and memory in rats.