Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability

Lyu, Dan; Tang, Ning; Womack, Andrew W; He, Yan; Lin, Qing

doi:10.4103/1673-5374.268929

Cited by 8 publications

(2 citation statements)

References 62 publications

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“…[3][4][5][6] However, over the last 20 years, experimental studies by our and other groups have shown that prolonged or repeatedly systemic (in vivo) administration of ketamine triggered neuronal apoptotic death in the developing brain. [7][8][9][10] Major areas affected are the frontal cortex (including the anterior cingulate cortex, ACC), parietal cortex, hippocampus and amygdala. 7,11 This neurodegenerative change is significantly linked to the subsequent deficits of learning and memory later in adulthood.…”

Section: Introductionmentioning

confidence: 99%

“…7,11 This neurodegenerative change is significantly linked to the subsequent deficits of learning and memory later in adulthood. 10,12,13 An in vitro electrophysiological study by our group suggests that the impairment of long-term potentiation of the synaptic transmission in the ACC contributes to the cognitive deficits. 14 However, the mechanisms still remain unclear underlying the selective vulnerability of the neonatal brain to ketamine-induced neuroapoptosis.…”

Section: Introductionmentioning

confidence: 99%

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The Increased Channel Activity of N-Methyl-D-Aspartate Receptors at Extrasynaptic Sites in the Anterior Cingulate Cortex of Neonatal Rats Following Prolonged Ketamine Exposure

Jin¹,

Wang²,

Lin³

2021

JPR

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Background: Ketamine is a dissociative anesthetic, commonly used for analgesia and anesthesia in a variety of pediatric procedures. It acts as a non-competitive antagonist to block ion channels of the N-methyl-D-aspartate receptors (NMDARs). Our previous study showed that repeated ketamine exposure developed a compensatory increase in NMDARmediated currents in neurons of the anterior cingulate cortex (ACC) of neonatal rats, and this increase was largely mediated by the GluN2B subunit-containing receptors, a predominant type of NMDARs during embryonic and early development of the brain. These data provide the molecular evidence to support that immature neurons are highly vulnerable to the development of apoptotic cell death after prolonged ketamine exposure. Methods: Using whole-cell patch-clamp electrophysiology in an in vitro preparation of rat forebrain slices containing the ACC, the present study aimed at further determining whether GluN2B-containing NMDARs at extrasynaptic sites of immature neurons were the major target of ketamine for developing a compensatory increase in NMDAR-mediated synaptic transmission. Results: Our major findings were that GluN2B subunits played a significant role in mediating ketamine-induced blockade of NMDAR-mediated currents in neonatal neurons and GluN2B-containing NMDARs expressed at extrasynaptic sites in neonatal neurons were the major player in compensatory enhancement of NMDAR-mediated currents after repeated ketamine exposure. Conclusion:These results provide new evidence to strongly indicate that GluN2Bcontaining NMDARs at extrasynaptic sites are the key molecule contributing to the high vulnerability of the neonatal brain to ketamine-induced neurotoxic effects.

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