The increment of annexin V-positive microvesicles versus annexin V-negative microvesicles in CSF of an animal model of Alzheimer's disease.

OBJECTIVE: Extracellular microvesicles (MVs) as a specific signaling molecule have received much attention in nervous system studies. Alterations in the tissue redox status in pathological conditions, such as Alzheimer's disease (AD), facilitate the translocation of cell membrane phosphatidylserine to the outer leaflet and lead to the MVs shedding. Annexin V binds with high affinity to phosphatidylserine. Some arguments exist about whether Annexin V-negative MVs should be considered in pathological conditions. MATERIAL AND METHOD: We compared the kinetics of two phenotypes of Annexin V-positive and Annexin V-negative MVs in the cerebrospinal fluid (CSF) of amyloid-ß (Aß)-treated male Wistar rats with flow cytometry technique. The Aß was injected bilaterally into the cerebral ventricles. Thioflavin T staining was used to confirm the presence of hippocampal Aß fibrils two weeks post-Aß injection. Levels of hippocampal interleukin-1ß were assessed as an inflammatory index. The CSF malondialdehyde (MDA) concentration was determined. The cognitive impairment and anxiety behaviors were assessed by object recognition and elevated plus maze tests, respectively. RESULTS: Elevation of MDA levels and a significant rise in the scoring of IL-1ß staining were found in the Aß group. The Aß induced anxiogenic behavior, impaired novel object recognition memory, and increased the CSF levels of the total number of MVs. The number of Annexin V-positive MVs was significantly higher than Annexin V-negative MVs in all groups. CONCLUSION: Data showed that Annexin V-positive MVs potentially have a significant contribution to the pathophysiology of the Aß-induced cognitive impairment. To catch a clear image of microvesicle production in pathological conditions, both phenotypes of Annexin V-positive and Annexin V-negative MVs should be analyzed and reported.

Increment of CSF fractalkine-positive microvesicles preceded the spatial memory impairment in amyloid beta neurotoxicity.

BACKGROUND: Fractalkine (CX3CL1) is a key chemokine, affects neuronal cell communication and involves in Alzheimer's disease pathogenesis. Microvesicles (MVs) participate in neuronal cells' cross-talk in physiological and pathological states. Microvesicles released in cerebrospinal fluid (CSF) may provide a valuable footprint of brain changes. Little information is available regarding the release of fractalkine-positive MVs (CX3CL1+ -MVs) in the nervous system. METHODS: We induced cognitive impairment by bilateral injection of amyloid-beta (Aß) into the cerebral ventricles. We analyzed the CSF by flow cytometry in two experiments (trained and untrained) to elucidate the presence of CX3CL1+ -MVs. The hippocampal TNF-α as an inflammatory factor was assessed by immunohistochemistry. RESULTS: The Aß induced spatial memory impairment after two weeks, verified by a decrease in the escape latency in Morris water maze test. It caused an increase in the anxiety-like behaviors demonstrated by a decrease in entries into the open arms of elevated plus maze test. The Aß increased the percent of the positive area for TNF-α staining. Histological evaluation of the hippocampus confirmed the tissue injuries. The CSF levels of CX3CL1+ -MVs, increased 2 and 7 days after Aß injection. The Aß increased the TNF-α staining and provided an inflammatory context to facilitate the MVs release. The rise of CX3CL1+ -MVs was transient and subsided after two weeks. Both trained and untrained experiments showed a similar rise pattern of CX3CL1+ -MVs. CONCLUSION: Increase of fractalkine-positive microvesicles preceded the cognitive impairment, more studies are required to approve the CX3CL1+ -MVs as a potential biomarker in the early diagnosis of Alzheimer's disease.

Chronic stress and Alzheimer's disease.

Stress is a key factor in the development and progress of diseases. In neurodegenerative conditions, stress management can play an important role in maintaining the quality of life and the capacity to improve. Neurodegenerative diseases, including Alzheimer's disease, cause the motor and cognitive malfunctions that are spontaneously stressful and also can disturb the neural circuits that promote stress responses. The interruption of those circuits leads to aggressive and inappropriate behavior. In addition, stress contributes to illness and may exacerbate symptoms. In this review, we present stress-activated neural pathways involved in Alzheimer's disease from a clinical and experimental point of view, as well as supportive drugs and therapies.

Portulaca oleracea L. prevents lipopolysaccharide-induced passive avoidance learning and memory and TNF-α impairments in hippocampus of rat.

There is a growing body of evidence that neuroinflammation can impair memory. It has been indicated that Portulaca oleracea Linn. (POL), possess anti-inflammatory activity and might improve memory disruption caused by inflammation. In this study the effect of pre-treatment with the hydro-alcoholic extract of POL on memory retrieval investigated in lipopolysaccharide (LPS) treated rats. Male Wistar rats (200-220g) received either a control diet or a diet containing of POL (400mg/kg, p.o.) for 14days. Then, they received injections of either saline or LPS (1mg/kg, i.p.). In all the experimental groups, 4h following the last injection, passive avoidance learning (PAL) and memory test was performed. The retention test was done 24h after the training and then the animals were sacrificed. Hippocampal TNF-α levels measured using ELISA as one criteria of LPS-induced neuroinflammation. The results indicated that LPS significantly impaired PAL and memory and increased TNF-α levels in hippocampus tissue. Pre-treatment with POL improved memory in control rats and prevented memory and TNF-α deterioration in LPS treated rats. Taken together, the results of this study suggest that the hydro-alcoholic extract of POL may improve memory deficits in LPS treated rats, possibly via inhibition of TNF-α and anti-inflammatory activity.