D-serine reduces memory impairment and neuronal damage induced by chronic lead exposure.

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From: Neural Regeneration Research(Vol. 16, Issue 5)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 5,276 words
Lexile Measure: 1360L

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Byline: Jian-Zhu. Bo, Ling. Xue, Shuang. Li, Jing-Wen. Yin, Zheng-Yao. Li, Xi. Wang, Jun-Feng. Wang, Yan-Shu. Zhang

Although exogenous D-serine has been applied as a neural regulatory intervention in many studies, the role played by D-serine in hippocampal injuries caused by lead exposure remains poorly understood. Rat models of chronic lead exposure were established through the administration of 0.05% lead acetate for 8 weeks. Simultaneously, rats were administered 30 or 60 mg/kg D-serine, intraperitoneally, twice a day. Our results showed that D-serine treatment shortened the escape latency from the Morris water maze, increased the number of times that mice crossed the original platform location, and alleviated the pathological damage experienced by hippocampal neurons in response to lead exposure. Although D-serine administration did not increase the expression levels of the N-methyl-D-aspartate receptor subtype 2B (NR2B) in the hippocampi of lead-exposed rats, 60 mg/kg D-serine treatment restored the expression levels of NR2A, which are reduced by lead exposure. These findings suggested that D-serine can alleviate learning and memory impairments induced by lead exposure and that the underlying mechanism is associated with the increased expression of NR2A in the hippocampus. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China (approval No. LX2018155) on December 21, 2018.


Lead, which is a ubiquitous environmental pollutant, causes a wide variety of long-lasting adverse effects in humans. Epidemiological and toxicological data have shown that lead exposure can impair the central nervous system (Sharma et al., 2015; Assi et al., 2016). A growing body of evidence has demonstrated that declining cognitive capacity and behavioral dysfunctions are the most common outcomes of lead exposure (Zeng et al., 2018; Santa Maria et al., 2019). Previous studies have shown that lead can induce learning and memory deficits associated with selective accumulation in the hippocampus, which is a basic anatomical structure associated with learning and memory (Zhou et al., 2018).

Evidence has suggested that damage to long-term potentiation (LTP) mechanisms, associated with N-methyl-D-aspartate receptor (NMDAR) injury, may represent the underlying mechanism that is responsible for neurologic damage observed in lead-exposed animals. Lead is a non-competitive NMDAR agonist capable of affecting the production and induction of LTP through the activation of the NMDAR, resulting in learning and memory impairments in rodents. Electrophysiological studies performed on isolated hippocampal neurons have shown that lead exposure can reduce the frequency of NMDAR single-channel opening. However, the mechanism through which lead causes NMDAR-mediated damage during the development of LTP in the hippocampus remains unclear. NMDAR is well-known to act as a crucial excitatory amino acid receptor in learning and memory processes. A previous study showed the removal of the NMDAR NR1 gene from the CA1 region in mice resulted in the development of learning and memory deficits associated with deficits in LTP (Wise and Lichtman, 2007). Lin et al. (2007) found that the disruption of the NMDAR downstream signaling pathway can prevent the induction of LTP and the formation of hippocampal-dependent memories. NMDAR is a hetero-oligomer, composed...

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Gale Document Number: GALE|A642710617