Neonatal Ethanol Exposure Impairs Trace Fear Conditioning and Alters <scp>NMDA</scp> Receptor Subunit Expression in Adult Male and Female Rats

Goodfellow, Molly J.; Abdulla, Khalid; Lindquist, Derick H.

doi:10.1111/acer.12958

Cited by 28 publications

(16 citation statements)

References 48 publications

(65 reference statements)

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“…Several studies have reported that the NMDA glutamate receptor complex plays a central role in synaptic plasticity and memory formation2122. Abnormal decreases in PSD-95 protein expression contribute to memory impairment in vitro 2324. This study found that PSD-95 expression was markedly increased in hypothermic mice after CCI compared with that measured in the TNG.…”

Section: Discussionmentioning

confidence: 53%

The Role of Posttraumatic Hypothermia in Preventing Dendrite Degeneration and Spine Loss after Severe Traumatic Brain Injury

Wang

Zhao

Jiang

et al. 2016

Sci Rep

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Posttraumatic hypothermia prevents cell death and promotes functional outcomes after traumatic brain injury (TBI). However, little is known regarding the effect of hypothermia on dendrite degeneration and spine loss after severe TBI. In the present study, we used thy1-GFP transgenic mice to investigate the effect of hypothermia on the dendrites and spines in layer V/VI of the ipsilateral cortex after severe TBI. We found that hypothermia (33 °C) dramatically prevented dendrite degeneration and spine loss 1 and 7 days after CCI. The Morris water maze test revealed that hypothermia preserved the learning and memory functions of mice after CCI. Hypothermia significantly increased the expression of the synaptic proteins GluR1 and PSD-95 at 1 and 7 days after CCI in the ipsilateral cortex and hippocampus compared with that of the normothermia TBI group. Hypothermia also increased cortical and hippocampal BDNF levels. These results suggest that posttraumatic hypothermia is an effective method to prevent dendrite degeneration and spine loss and preserve learning and memory function after severe TBI. Increasing cortical and hippocampal BDNF levels might be the mechanism through which hypothermia prevents dendrite degeneration and spine loss and preserves learning and memory function.

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Section: Discussionmentioning

confidence: 53%

The Role of Posttraumatic Hypothermia in Preventing Dendrite Degeneration and Spine Loss after Severe Traumatic Brain Injury

Wang

Zhao

Jiang

et al. 2016

Sci Rep

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“…NMDAR has been subject of study also in the context of fear memory. Even if most of the studies support the idea that GluN2B is the subunit that is primarily involved in this kind of memory process [142][143][144][145][146], recently some studies have also pointed out an involvement of GluN2A-containing NMDARs. The group of Luo demonstrated that interfering with the activity-dependent insertion of GluN2A mediated by the ER chaperone Bip in the dorsal hippocampus was sufficient to impair the acquisition of fear conditioning test, suggesting that the interaction between the two proteins is crucial for fear memory formation [107].…”

Section: Role Of Glun2a In Learning and Memorymentioning

confidence: 99%

Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity

Franchini

Carrano

Luca

et al. 2020

IJMS

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N-Methyl-d-Aspartate Receptors (NMDARs) are ionotropic glutamate-gated receptors. NMDARs are tetramers composed by several homologous subunits of GluN1-, GluN2-, or GluN3-type, leading to the existence in the central nervous system of a high variety of receptor subtypes with different pharmacological and signaling properties. NMDAR subunit composition is strictly regulated during development and by activity-dependent synaptic plasticity. Given the differences between GluN2 regulatory subunits of NMDAR in several functions, here we will focus on the synaptic pool of NMDARs containing the GluN2A subunit, addressing its role in both physiology and pathological synaptic plasticity as well as the contribution in these events of different types of GluN2A-interacting proteins.

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“…In separate ECON and EKYN rats at both ages, we studied impairment of executive function, which is thought to be predictive of SZ progression and functional outcome (Green, 1996; Green et al, 2004). To this end, we assessed trace fear conditioning (TFC), a cognitively challenging form of classical (Pavlovian) conditioning that can be readily studied in both juvenile and adult rodents (Barnet and Hunt, 2005; Goodfellow et al, 2016) and that depends upon the integrity of interactions between the hippocampus and the PFC (Raybuck and Gould, 2010). …”

Section: Introductionmentioning

confidence: 99%

Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding

et al. 2016

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Levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine (±7nACh) and antagonist at glutamatergic N-methyl-D-aspartate (NMDA) receptors, are elevated in the brain of patients with schizophrenia (SZ). In rats, dietary exposure to KYNA’s immediate precursor kynurenine during the last week of gestation produces neurochemical and cognitive deficits in adulthood that resemble those seen in patients with SZ. The present experiments examined whether prenatal kynurenine exposure results in age-dependent changes in the kynurenine pathway (KP), expression of selected receptors, and cognitive function. Pregnant dams were fed unadulterated mash (progeny = ECON) or mash containing kynurenine (100 mg/day; progeny = EKYN) from embryonic day (ED) 15 to 22. Male offspring were assessed as juveniles, i.e. prior to puberty (postnatal day [PD] 32), or as adults (PD70) for brain KYNA levels, ±7nACh and NMDA receptor gene expression, and performance on a trace fear conditioning (TFC) task. KYNA levels were comparable between juvenile ECON and EKYN rats whereas EKYN adults exhibited a ~3-fold increase in brain KYNA relative to ECONs. NR2A expression was persistently reduced (30–40%) in EKYN rats at both ages. Compared to ECON adults, there was a 50% reduction in NR1, and a trend toward decreased ±7nACh expression, in adult EKYN rats. Surprisingly, juvenile EKYN rats performed significantly better in the TFC paradigm than controls, whereas adult EKYN animals showed the predicted deficits. Collectively, our results provide evidence that elevated KYNA in the fetal brain alters neuronal development and causes age-dependent effects on neurochemistry and cognitive performance.

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Neonatal Ethanol Exposure Impairs Trace Fear Conditioning and Alters NMDA Receptor Subunit Expression in Adult Male and Female Rats

Abstract: EtOH-induced changes in DH NMDAR subunit expression-particularly synaptic GluN2B, which is critical for TFC-are proposed to weaken long-term memory consolidation and, during behavioral testing, diminish CS-evoked freezing behavior.

Cited by 28 publications

References 48 publications

The Role of Posttraumatic Hypothermia in Preventing Dendrite Degeneration and Spine Loss after Severe Traumatic Brain Injury

The Role of Posttraumatic Hypothermia in Preventing Dendrite Degeneration and Spine Loss after Severe Traumatic Brain Injury

Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity

Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding

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