Amelioration of amyloid β-induced cognitive deficits by Zataria multiflora Boiss. Essential oil in a rat model of Alzheimer's disease

Introduction: The limitations of current Alzheimer's disease (AD) therapeutics have prompted investigation into innovative therapeutics focused on antiinflammatory, antioxidant, and neuroprotective agents including those from medicinal plants. Numerous plants have been tested for their potential for alleviating symptoms of AD. Aims: Zataria multiflora Boiss. (ZM) a member of Lamiaceae family has been used in Iranian traditional medicine for its beneficial effects on mental abilities. Therefore, the effect of its essential oil was evaluated in a rat model of AD. Methods: Amyloid β‐protein (Aβ) fragment 25–35 was injected bilaterally in the CA1 region of rats hippocampus and the effect of different doses of ZM essential oil (50, 100, or 200 μL/kg) on cognitive function was investigated in the Morris water maze. Acute toxicity of the essential oil was also studied. Results: The results showed increases in escape latency, traveled distance, heading angle, and decreases in target quadrant entries in Aβ‐received groups as compared to the control group. This impairment was reversed by ZM essential oil. The results of acute toxicity testing revealed that the calculated LD50 (1264.9 μL/kg) is much higher than the therapeutic dose (100 μL/kg). Conclusions: It seems that antioxidant, antiinflammatory, and anticholinesterase activities of ZM or its main constituents might contribute to its beneficial effects in this model. Our findings suggest that ZM may be a potentially valuable source of natural therapeutic agents for the treatment of AD. However, further investigations are necessary to establish its clinical efficacy and potential toxicity, before any recommendations concerning its use as a medication in the treatment of AD.     

Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain

There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na⁺/K⁺ ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.     

Effects of tamoxifen on tricarboxylic acid cycle enzymes in the brain of rats submitted to an animal model of mania induced by amphetamine

The neurobiological basis of bipolar disorder (BD) remains unknown; nevertheless, mitochondrial dysfunction has been identified in this disorder. Inactivation of any step in the tricarboxylic acid (TCA) cycle can impair mitochondrial ATP production. There is recent evidence indicating that PKC is an important therapeutic target for bipolar disorder. Therefore, we evaluated the effects of tamoxifen (TMX—a PKC inhibitor) on the activities of enzymes in the TCA cycle of rat brains subjected to an animal model of mania induced by amphetamine. In the reversal treatment, Wistar rats were first treated with d-AMPH or saliratsne (Sal) for 14 days. Thereafter, between days 8 and 14, the rats were administered TMX or Sal. The citrate synthase, succinate dehydrogenase, and malate dehydrogenase were evaluated in the frontal cortex, hippocampus, and striatum. The d-AMPH administration inhibited TCA cycle enzymes activity in all analyzed structures, and TMX reversed d-AMPH-induced dysfunction. In addition, we observed a negative correlation between d-AMPH-induced hyperactivity and the activity of these enzymes in the rat's brain. These findings suggested that TCA cycle enzymes inhibition can be an important link for the mitochondrial dysfunction seen in BD, and TMX exert protective effects against the d-AMPH-induced TCA cycle enzymes dysfunction.     

Cognitive impairments in patients with cerebrovascular risk factors: A comparison of Mini Mental Status Exam and Montreal Cognitive Assessment

Objective and background

Recent evidence suggests that cerebrovascular risk factors are contributing factors, not only to vascular cognitive decline, but also for Alzheimer's disease. The study aim was to compare Montreal Cognitive Assessment (MoCA) and MMSE tests in subjects with cerebrovascular risk factors.

Patients and methods

Fifty patients with cerebrovascular risk factors were administrated the MMSE and MoCA tests. Data collected for all subjects and the results were compared.

Results

Cognitive impairments revealed on both tests were more frequent in females, and correlated with the level of education (for MoCA r = 0.75, p = 0.001 and for MMSE r = 0.662, p = 0.001). Mean values of MoCA score were significantly lower in patients with two or more cerebrovascular risk factors compared with those with only one risk factor (19.92 ± 5.99 versus 23.81 ± 4.06; p = 0.049), a finding that was not evidenced by MMSE.

Conclusions

The most frequent impaired domain in MMSE (for scores both less and more than 26) was attention; but in MoCA the most frequent impaired domains were delayed recall (for scores above 26), and visuo-executive (for scores ≤26), which is a common domain involved in vascular cognitive decline. MoCA may be superior to MMSE in early detection of cognitive decline in patients with vascular risk factors.     

Chronic neuroprotective effects of low concentration lithium on SH-SY5Y cells:possible involvement of stress proteins and gene expression

To investigate the molecular mechanism underlying the neuroprotective effect of lithium on cells, in this study, we exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate(Li2CO2) for 25–50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2(PKM2) and calmodulin 3(CaM 3) expression levels were significantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II(CK2), threonine/tyrosine phosphatase 7(PYST2), and dopamine beta-hydroxylase(DBH) expression levels were significantly up-regulated. Besides, western blot analysis of stress proteins(HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins: a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modifications of proteins cited above.     

Contribution des facteurs génétiques et nutritionnels dans les hyperhomocystéinémies dans la population algérienne saine

The particular genetic polymorphisms associated to homocysteine metabolism enzymes, or more usually, a relative lack in different vitamins B group, are the main cause of the increase in this sulfur amino acid in the blood. As a fact, hyperhomocysteinemia are associated to many pathologies. The aim of this study is to determine the frequencies of the different genotypes caused by these polymorphisms, folate and vitamin B12 status and their eventual connections to hyperhomocysteinemia among a healthy adult population. The investigation has been applied to 165 apparently healthy volunteers. The homocysteine concentration was determined by IMx fluorescence polarization immunoassay. The genotypes determination was done by real-time PCR (RT-PCR) (Light Cycler 480). Folates and vitamin B12 were analyzed by SimulTRAC-SNB immunoassay. The homocysteine level was 14,69 ± 7,30 μmol/L. 22.5% of the subjects exhibited a moderate hyperhomocysteinemia (> 15 μmol/L). The major nutritional determinants of the plasmatic homocysteine rates among these subjects were blood folate and vitamin B12 levels. Blood homocysteine was the highest for the homozygote (TT) individuals for the MTHFR gene than for the heterozygote (CT) and homozygote (CC) subjects in particular for the lowest blood folate quartile. These two assessments have to be taken in consideration when evaluating the predisposition of the Algerian population for morbid and/or mortal pathologies and allow emphasizing on the necessity of screening out and eventually treating vitamin deficiencies on folates vitamin B12.