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Abstract Many patients with sporadic Alzheimer's disease (AD) suffer from memory impairment, anxiety- and depression. The systemic utility of N-Methyl- d -Aspartate (NMDA) receptor antagonists has been shown to be potential therapeutic target for memory loss in AD. However, there is no evidence that shows whether NMDA receptor antagonists have the same effects when these blockers are directly used within the brain regions including hippocampus. It might be an urgent to further explore the therapeutic role of NMDA receptor antagonists in behavioral abnormalities such as anxiety and depression in AD. The aim of this study was to determine whether blockade of the hippocampal NMDA receptors could attenuate neurobehavioral abnormalities in rats with sporadic AD. Twelve days after AD induction by streptozotocin (STZ), animals received either vehicle or MK-801 (NMDA receptor antagonist) in the hippocampus for 10 days. Two or five days after the last MK-801 treatment, spatial memory, anxiety- and depression-related behaviors, and inflammatory cytokines (interleukin-(IL)-6, IL-1β and tumor necrosis factor (TNF)-α) were evaluated. Our findings indicated that STZ treatment significantly elevated hippocampal inflammation, impaired spatial memory, and increased anxiety- and depression-related symptoms in rats. Interestingly, the hippocampal NMDA receptor blockade improved these neurobehavioral phenotypes and decreased inflammatory cytokines in the hippocampus of STZ-treated rats. Hippocampal NMDA receptors might be involved in neurobehavioral abnormalities via inflammation in sporadic AD. Highlights • Sporadic Alzheimer-like disease was induced by ICV injection of streptozocin (STZ). • Hippocampal NMDA receptor blockade improved memory in STZ-treated rats. • Hippocampal NMDA receptor blockade decreased anxiety behavior in STZ-treated rats. • Hippocampal NMDA receptor blockade reduced depression symptoms in STZ-treated rats. • NMDA receptor blockade reduced hippocampal inflammation in STZ-treated rats. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a common neurodegenerative disorder in elderly people with an impairment of cognitive decline and memory loss. β-amyloid (Aβ) as a potent neurotoxic peptide has a pivotal role in the pathogenesis of AD. This disease begins with impairment in synaptic functions before developing into later neuro-degeneration and neuronal loss. The aim of this study was to evaluate the synaptic plasticity and electrophysiological function of granule cells in hippocampal dentate gyrus (DG) after intracere broventricular (i.c.v.) administration of aggregated Aβ (1-42) peptide in vivo. Methods: Animals were divided to control and Aβ (1-42) groups. Long-term potentiation (LTP) in perforant path-DG synapses was assessed in order to investigate the effect of aggregated Aβ (1-42) on synaptic plasticity. Field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured. Results: Administration of Aβ (1-42) significantly decreased fEPSP slope and PS amplitude in Aβ (1-42) group comparing with the control group and had no effect on baseline activity of neurons. Conclusion: The present study indicates that administration of aggregated form of Aβ (1-42) into the lateral ventricle effectively inhibits LTP in granular cells of the DG in hippocampus in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer׳s disease (AD) is a neurodegenerative disorder with a progressive cognitive decline and memory loss. Multiple pathogenetic factors including aggregated β-amyloid (Aβ), neurofibrillary tangles (NFTs), cholinergic dysfunction and oxidative stress are involved in AD. Aβ, a major constituent of the senile plaques, is a potent neurotoxic peptide and has a pivotal role in cognitive deficit and reduced synaptic plasticity in AD. In the present study we examined the protective effect of troxerutin, as a multipotent bioflavonoid, on Aβ (1–42)-induced impairment of evoked field potential in hippocampal DG neurons. Male Wistar rats were divided into four groups including Aβ (42–1), Aβ (1–42), Aβ (1–42) plus troxerutin and Aβ (42–1) plus troxerutin groups. Aβ was injected intracerebroventricularly (i.c.v.) into right lateral ventricle and after two weeks the evoked field potential recorded from perforant path-DG synapses to assess paired pulse paradigm and long term potentiation (LTP). Administration of Aβ (1–42) drastically attenuated the LTP of DG neurons, while there was no significant difference in evoked field potentials between Aβ (1–42) plus troxerutin group with respect to Aβ (42–1) group. This study revealed that troxerutin improves the synaptic failure induced by Aβ peptide and can be introduced as a promising multi-potent pharmacological agent in prevention or treatment of AD in the future. [Copyright &y& Elsevier]