Hippocampal synaptic plasticity impairment and melatonin synthesis reduction in cognitive decline of a rodent model of Alzheimer’s disease-like pathology

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Abstract
Melatonin, the pineal gland hormone, is produced in several extra-pineal tissues. The arylalkylamine N-acetyltransferase (AANAT) enzyme activity determines the overall rate of tissue melatonin synthesis. A decline in AANAT enzyme activity during acute amyloid-β (Aβ) neurotoxicity and reduced melatonin levels in Alzheimer’s patients have been reported. These findings raise the question of whether brain melatonin synthesis is altered during cognitive decline. We investigated whether cognitive impairment induced by Aβ administration could affect the activation status of AANAT, a key hippocampal enzyme of melatonin synthesis. Male Wistar rats received intra-cerebroventricular Aβ injection. Two weeks after Aβ administration, the neuroinflammation was assessed by interleukin-1 (IL-1β) immunohistochemical staining. Hippocampal long-term potentiation (LTP) was evaluated using the technique of local field recording. The cognitive function was assessed using the Morris water maze behavioral test.The hippocampal AANAT activation status was assessed by Western blotting, and HPLC was used for melatonin level analysis. Aβ-induced spatial memory and LTP impairments were confirmed by increased escape latencies and alterations in the fEPSP slope. The Aβ provided a neuroinflammatory context, demonstrated by increased in the IL-1𝛽 staining. These alterations were accompanied by a reduction in the activation status of AANAT, as indicated by the p-AANAT/total AANAT ratio, in both the electrophysiology and behavioral experimental groups.These data suggest that the local activation status of AANAT may be contributed in the cognitive function of the hippocampus in a rodent model of cognitive decline induced by Aβ administration. Graphical abstract
Funding Information
  • Tehran University of Medical Sciences (98-02-226-43559)

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