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

Abstract

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.

Evaluation of the Role of Melatonin in Dietary Restriction Effects on Spatial Memory Impairment Induced by Streptozotocin (STZ) in Male Rats

“…In this study, it was observed that administration of melatonin did not have significant effect on spatial memory impairment in STZ-treated rats. This observation was against a previous study claiming that exogenous melatonin can improve spatial memory in STZ-treated rats (20)(21)(22).…”

“…Previous studies have shown that dietary restriction may change melatonin production and secretion and can also shift the production and secretion time of melatonin when the SCN clock is lacking (18). Owing to the welldescribed neuroprotective effects of melatonin in some studies (19)(20)(21)(22)(23) and the fact that melatonin level is declined in aging and specially in Alzheimer's (17), there seem to be at least some dietary restriction effects related to melatonin level changes. To investigate such a hypothesis, melatonin receptors (MT1, MT2) antagonist (luzindole) was used.…”

“…Restricted feeding restores not only a rhythmic transcription of the rate-limiting enzyme for melatonin biosynthesis [aryl-alkylamine-Nacetyl-transferase (AANAT)] but also a rhythmic synthesis of melatonin in the pineal gland (18). Neuroprotective effects of melatonin have been shown in several studies (19)(20)(21)(22)(23). Many studies have reported disrupted circadian rhythms and melatonin production in aging and in Alzheimer's disease.…”

Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases β-amyloid by enhancing expression of presenilin-2

“…Nissl staining of the neurons showed comparable cell number and density in the hippocampus and cortex of the rat brains in all the three groups (Figure 2), indicating that the learning and memory impairment in H. pylori filtrate-injected rats is induced by disturbed neuronal function but not by neuron loss. Aβ level is increased in AD brains and induces cognitive deficits in AD animal models (Billings et al, 2005; Liu et al, 2013). To further disclose the underlying mechanisms for memory deficit induced by H. pylori filtrate, we detected the Aβ 40 and Aβ 42 levels in the rat brains.…”

GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease

“…By using in vivo preparations, it has been proposed that reduction of septal cholinergic and glutamatergic inputs onto GABAergic septal neurons may reduce the population of rhythmically bursting GABAergic neurons and suggest that GABAergic neurons are dysfunctional in Aβ-treated rats (Colom et al, 2010). Similarly, hippocampal Aβ 1 - 40/31 - 35 injections induce a significant impairment of spatial memory in rats and concomitant reduction in the hippocampal theta rhythm (Liu et al, 2013). Aβ effects are associated with GABAergic neurons dysfunction and greatly weakened septal theta transmission to the hippocampus rather than interfere with its generation.…”