The neuroprotection of Rattin against amyloid β peptide in spatial memory and synaptic plasticity of rats.

Rattin, a specific derivative of humanin in rats, shares the ability with HN to protect neurons against amyloid β (Aβ) peptide-induced cellular toxicity. However, it is still unclear whether Rattin can protect against Aβ-induced deficits in cognition and synaptic plasticity in rats. In the present study, we observed the effects of Rattin and Aβ31-35 on the spatial reference memory and in vivo hippocampal Long-term potentiation of rats by using Morris water maze test and hippocampal field potential recording. Furthermore, the probable molecular mechanism underlying the neuroprotective roles of Rattin was investigated. We showed that intra-hippocampal injection of Rattin effectively prevented the Aβ31-35-induced spatial memory deficits and hippocampal LTP suppression in rats; the Aβ31-35-induced activation of Caspase-3 and inhibition of STAT3 in the hippocampus were also prevented by Rattin treatment. These findings indicate that Rattin treatment can protect spatial memory and synaptic plasticity of rats against Aβ31-35-induced impairments, and the underlying protective mechanism of Rattin may be involved in STAT3 and Caspases-3 pathways. Therefore, application of Rattin or activation of its signaling pathways in the brain might be beneficial to the prevention of Aβ-related cognitive deficits.

Wang ZJ ，Han WN ，Yang GZ ，Yuan L ，Liu XJ ，Li QS ，Qi JS ... -  《-》

Melatonin protects against amyloid-β-induced impairments of hippocampal LTP and spatial learning in rats.

Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, leads to progressive loss of memory and cognitive deficits. Amyloid-β protein (Aβ) in the brain is thought to be the main cause of memory loss in AD. Melatonin, an indole hormone secreted by the pineal gland, has been reported to produce neuroprotective effects. We examined whether melatonin could protect Aβ-induced impairments of hippocampal synaptic plasticity, neuronal cooperative activity, and learning and memory. Rats received bilateral intrahippocampal injection of Aβ1-42 or Aβ31-35 followed by intraperitoneal application of melatonin for 10 days, and the effects of chronic melatonin treatment on in vivo hippocampal long-term potentiation (LTP) and theta rhythm and Morris water maze performance were examined. We showed that intrahippocampal injection of Aβ1-42 or Aβ31-35 impaired hippocampal LTP in vivo, while chronic melatonin treatment reversed Aβ1-42- or Aβ31-35-induced impairments in LTP induction. Intrahippocampal injection of Aβ31-35 impaired spatial learning and decreased the power of theta rhythm in the CA1 region induced by tail pinch, and these synaptic, circuit, and learning deficits were rescued by chronic melatonin treatment. These results provide evidence for the neuroprotective action of melatonin against Aβ insults and suggest a strategy for alleviating cognition deficits of AD.

Liu XJ ，Yuan L ，Yang D ，Han WN ，Li QS ，Yang W ，Liu QS ，Qi JS ... -  《-》

[Gly14]-Humanin Protects Against Amyloid β Peptide-Induced Impairment of Spatial Learning and Memory in Rats.

Yuan L ，Liu XJ ，Han WN ，Li QS ，Wang ZJ ，Wu MN ，Yang W ，Qi JS ... -  《-》

Colivelin ameliorates amyloid β peptide-induced impairments in spatial memory, synaptic plasticity, and calcium homeostasis in rats.

Amyloid β peptide (Aβ) has been thought to be neurotoxic and responsible for the impairment of learning and memory in Alzheimer's disease (AD). Humanin (HN), a 24 amino acid polypeptide first identified from the unaffected occipital lobe of an AD patient, is believed to be neuroprotective against the AD-related neurotoxicity. In this study, we investigated the neuroprotective effects of Colivelin (CLN), a novel HN derivative, against Aβ by using behavioral test, in vivo electrophysiological recording, and intracellular calcium imaging. Our results showed that intrahippocampal injection of CLN (0.2 nmol) effectively prevented Aβ25-35 (4 nmol)-induced deficits in spatial learning and memory of rats in Morris water maze test; the suppression of in vivo hippocampal long term potentiation (LTP) by Aβ25-35 was nearly completely prevented by CLN; in addition, CLN pretreatment also effectively inhibited Aβ25-35-induced calcium overload in primary cultured hippocampal neurons. These results indicate that CLN has significant neuroprotective properties against Aβ, and CLN may holds great promise for the treatment and prevention of AD.

Wu MN ，Zhou LW ，Wang ZJ ，Han WN ，Zhang J ，Liu XJ ，Tong JQ ，Qi JS ... -  《-》

Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP.

Tong JQ ，Zhang J ，Hao M ，Yang J ，Han YF ，Liu XJ ，Shi H ，Wu MN ，Liu QS ，Qi JS ... -  《-》