Effects Of Amyloid-beta Research Articles

Alzheimer’s Disease and Neuronal Network Activity

The amyloid beta-peptide theory of Alzheimer's Disease has helped to advance our understanding of the disease tremendously. A new area of research focuses on the changes in neuronal network activity that take place and may contribute to the clinical and pathological picture of Alzheimer's Disease. An apparent symptom of altered neuronal network activity in Alzheimer's Disease is an increased frequency in epileptic seizures that is observed both in human patients and in mouse models of Alzheimer's Disease. A root cause for altered network activity may be amyloid beta itself by its ability to alter synaptic (glutamatergic) transmission and to impair the induction of long-term potentiation. It is on this aspect of Alzheimer's Disease research that the current issue of NeuroMolecular Medicine will focus. Reviews will discuss the basic research and clinical aspects of the issue such as the effects of amyloid beta on synaptic transmission and neuronal networks, as well as the changes in functional MRI activation patterns observed in early stages of Alzheimer's Disease and the frequency and relevance of epileptic seizures in Alzheimer's Disease patients.

Protective effects of the sigma agonist Pre-084 in the rat retina

Aim:With the rationale that amyloid beta (AB) is toxic to the retina, we here assessed the role of TRAIL, a mediator of AB toxicity and related signal transduction, in a...

Effects of Aβ25–35 on neurogenesis in the adult mouse subventricular zone and dentate gyrus

It has been demonstrated that neuorgenesis driven by neural precursor cells persists well into the adult period. This study was to observe the effects of Amyloid-beta (25–35) peptide (Aβ25–35) on neurogenesis in the subventricular zone and dentate gyrus of adult mouse brain. Aggregated Aβ25–35(1 mg/ml, 3 μl) was injected into the lateral ventricle of adult mouse. Animals were transcardially perfused with 4% paraformaldehyde in PBS, respectively at 5, 10, 20, 30 days after the Aβ25–35 injection. All the animals were injected with BrdU (50 mg/kg, i. p) to label the neural precursor cells 24 h before the each perfusion. NeuN immunofluorescence and BrdU immunohistology were performed. It was found that Aβ25–35 could injure the mature neurons and decrease the number of NeuN positive neurons. It also showed that Aβ25–35 inhibited neurogenesis and significantly decreased the number of BrdU positive cells in the dentate gyrus of hippocampus, but it had no obvious effects on neurogenesis in the subventricular zone. The present results indicated that Aβ25–35 could impair neurogenesis in the hippocampus of adult mouse brain.

Effects of amyloid-beta on cholinergic and acetylcholinesterase-positive cells in cultured basal forebrain neurons of embryonic rat brain

The neurotoxic effects of amyloid-β 1–42 and amyloid-β 25–35 (Aβ) on cholinergic and acetylcholinesterase-positive neurons were investigated in primary cultures derived from embryonic 18-day-old rat basal forebrain. After various time intervals, the cultures were treated with 1, 5, 10 or 20 μM Aβ for different time periods. The cholinergic neurons and their axon terminals were revealed by vesicular acetylcholine transporter immunohistochemistry and the cholinoceptive cells by acetylcholinesterase histochemical staining. To assess the toxic effects of these Aβ peptides on the cholinergic neurons, image analysis was applied for quantitative determination of the numbers of axon varicosities/terminals and cells. The results demonstrate that, following treatment with 1 or 5 μM Aβ for 5, 10, 30, 60 or 120 min, no changes in vesicular acetylcholine transporter immunohistochemical staining were observed. However, after treatment for 30 min with 10 or 20 μM Aβ, the number of stained axon varicosities was reduced, and treatment for 2 h they had disappeared. In contrast, vesicular acetylcholine transporter-positivity could be seen in some of the neuronal perikarya even after 3 days after treatment. The acetylcholinesterase staining was homogeneously distributed in the control neurons. After Aβ treatment, the histochemical reaction end-product was detected in some of the neuronal perikarya or in the dendritic processes near to the soma. It is concluded that the neurotoxic effects of Aβ appear more rapidly in the cholinergic axon terminals than in the cholinergic and acetylcholinesterase-positive neuronal perikarya.

Alzheimer's Abeta1-40 peptide modulates lipid synthesis in neuronal cultures and intact rat fetal brain under normoxic and oxidative stress conditions.

The effect of amyloid beta (Abeta), the major constituent of the Alzheimer's (AD) brain on lipid metabolism was investigated in cultured nerve cells and in a fetal rat brain model. Differentiated (NGF) and undifferentiated PC12 cells or primary cerebral cell cultures were incubated with [14C]acetate in the absence or presence of Abeta1-40. Incorporation of label into lipid species was determined after lipid extraction and TLC separation. Phosphatidylcholine (PC) and phosphatidylserine (PS) synthesis was increased by Abeta1-40, in a dose dependent manner, an effect which was more pronounced in differentiated PC12 cells. A significant proportion of radioactivity (5-6%) was released into the medium with a radioactivity distribution similar to that of the cellular lipids. Cholesterol and PC were the highest labeled medium lipids. Increasing Abeta1-40 concentration up to 0.1 microg/ml in cerebral cells but not in PC12 cells, caused a relative increase (1.5 fold) in release of PS, while that of PE decreased. Stimulation of PS release may possibly be associated with apoptotic cell death. Abeta1-40 peptide (5 microg) was administered intraperitoneally into rat fetuses (18 days gestation) along with [14C]acetate (2 microCi/fetus). After 24 h, the maternal-fetal blood supply was occluded for 20 min (ischemia) followed by 15 min reperfusion. Fetuses were killed and liver and brain tissue subjected to lipid extraction and radioactivity determination after TLC. Abeta1-40 peptide increased synthesis of different classes of lipids up to 20-40% in brain tissue compared to controls. Labeling of liver lipids was decreased by Abeta1-40 by 20-30%. A general decrease in synthesis of lipids was observed after ischemia/reperfusion. Our data suggest that Abeta1-40 peptide regulates normal lipid biosynthesis but under ischemia it compromises it. The latter finding may confirm the oxidative stress etiology in AD and suggests that Abeta1-40 modulation of lipid metabolism may have Alzheimer's pathological relevance, particularly at high peptide concentrations.