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Acute Melamine Affects Spatial Memory Consolidation via Inhibiting Hippocampal NMDAR-Dependent LTD in Rats
1Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Abstract:
Converging evidence supported that melamine could impair learning and memory and hippocampal function by mechanisms as yet unknown. The aim of this study was to obtain the first clues of how melamine affected spatial cognition, and how it may act on hippocampal function to modulate plasticity. Morris water maze test was used to probe spatial learning and memory. Pharmacological approaches were employed to modulate NMDAR and AMPAR-dependent long-term synaptic plasticity of rats' hippocampal CA1 region. Both systemic and intrahippocampal application of melamine impaired the formation of long-term spatial memory, particularly consolidation memory. The reduced expression of NMDA-NR1 and -NR2B subunits, but not AMPAR subunits, was presented. Meanwhile melamine inhibited inductions of long-term potentiation (LTP) and long-term depression (LTD) via mediating NMDARs. Notably, the specific role of hippocampal CA1 LTD in regulation of spatial consolidation has been observed in normal physiology. Moreover, the prevention of inhibited hippocampal CA1 LTD but not LTP could rescue the disruption of long-term spatial memory of the melamine-treated rats. Taken together, our findings suggested that acute melamine exposure impaired spatial memory consolidation via disrupting hippocampal NMDAR-dependent LTD. This provided an important insight into the neurophysiology of melamine-related and other psychiatric disorders.
Insights
Melamine exposure impairs spatial memory consolidation by disrupting hippocampal N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD). This finding offers insights into melamine
Area of Science:
- Neuroscience
- Toxicology
- Cognitive Science
Background:
- Melamine is known to impair learning and memory.
- The precise mechanisms underlying melamine's neurotoxicity, particularly on hippocampal function and plasticity, remain largely unknown.
Purpose of the Study:
- To investigate how melamine affects spatial cognition.
- To elucidate the impact of melamine on hippocampal function and synaptic plasticity.
Main Methods:
- Utilized the Morris water maze test to assess spatial learning and memory in rats.
- Employed pharmacological methods to modulate N-methyl-D-aspartate receptor (NMDAR) and AMPA receptor (AMPAR)-dependent synaptic plasticity in the hippocampal CA1 region.
- Analyzed the expression of NMDAR and AMPAR subunits.
Main Results:
- Systemic and intrahippocampal melamine administration impaired long-term spatial memory formation, especially memory consolidation.
- Melamine reduced the expression of NMDA-NR1 and -NR2B subunits, but not AMPAR subunits.
- Melamine inhibited the induction of long-term potentiation (LTP) and long-term depression (LTD) by mediating NMDARs.
- Preventing the inhibition of hippocampal CA1 LTD, but not LTP, rescued the spatial memory deficits.
Conclusions:
- Acute melamine exposure impairs spatial memory consolidation by disrupting hippocampal NMDAR-dependent LTD.
- This study provides crucial insights into the neurophysiological basis of melamine-induced cognitive deficits and potential links to psychiatric disorders.
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