Metabolism Changes During Aging in the Hippocampus and Striatum of Glud1 (Glutamate Dehydrogenase 1) Transgenic Mice

Choi, In Young; Lee, Phil; Wang, Wen Tung; Hui, Dongwei; Wang, Xinkun; Brooks, William M.; Michaelis, Elias K.

doi:10.1007/s11064-014-1239-9

Cited by 13 publications

(8 citation statements)

References 72 publications

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“…In previous studies, we observed small increases in Glu levels in the brains of the Glud1 tg as compared with wt mice [22, 55]. However, statistical analyses of the data in our current study did not reveal statistically significant differences in the baseline measurements of Glu between wt and tg mice.…”

Section: Discussioncontrasting

confidence: 77%

Effects of Ethanol Exposure on the Neurochemical Profile of a Transgenic Mouse Model with Enhanced Glutamate Release Using In Vivo 1H MRS

et al. 2018

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Ethanol (EtOH) intake leads to modulation of glutamatergic transmission, which may contribute to ethanol intoxication, tolerance and dependence. To study metabolic responses to the hyper glutamatergic status at synapses during ethanol exposure, we used Glud1 transgenic (tg) mice that over-express the enzyme glutamate dehydrogenase (GDH) in brain neurons and release excess glutamate (Glu) in synapses. We measured neurochemical changes in the hippocampus and striatum of tg and wild-type (wt) mice using proton magnetic resonance spectroscopy before and after the animals were fed with diets within which EtOH constituting up to 6.4% of total calories for 24 weeks. In the hippocampus, the EtOH diet led to significant increases in concentrations of EtOH, glutamine (Gln), Glu, phosphocholine (PCho), taurine, and Gln+Glu, when compared with their baseline concentrations. In the striatum, the EtOH diet led to significant increases in concentrations of GABA, Gln, Gln+Glu, and PCho. In general, neurochemical changes were more pronounced in the striatum than the hippocampus in both tg and wt mice. Overall neurochemical changes due to EtOH exposure were very similar in tg and wt mice. This study describes time courses of neurochemical profiles before and during chronic EtOH exposure, which can serve as a reference for future studies investigating ethanol-induced neurochemical changes.

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Section: Discussioncontrasting

confidence: 77%

Effects of Ethanol Exposure on the Neurochemical Profile of a Transgenic Mouse Model with Enhanced Glutamate Release Using In Vivo 1H MRS

et al. 2018

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“…These opposing effects may have mitigated any age-related difference in overall Glx concentration here, but an underlying age-related imbalance may still account for the relationship with RAVLT performance. Outside of the hippocampus, age-related decreases in glutamate have been reported in the striatum (Zahr et al, 2008; but see Choi et al (2014) for the opposite pattern), but not the cerebellum (Zahr et al, 2008, 2013), emphasizing the possible regional specificity of these metabolic imbalances. Additionally, the opposing dynamics of the glutamate-glutamine cycle may be completely masked by the combined Glx metric.…”

Section: Discussionmentioning

confidence: 98%

3T hippocampal glutamate-glutamine complex reflects verbal memory decline in aging

Nikolova

Stark

2017

Neurobiology of Aging

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The hippocampus is a critical site for alterations that are responsible for age-related changes in memory. Here, we present a relatively novel approach of examining the relationship between memory performance and Glutamate-Glutamine levels using short echo time magnetic resonance spectroscopy (MRS). Specifically, we investigated the relationship between Glx (a composite of glutamate and glutamine) levels in the hippocampus, performance on a word recall task and resting state functional connectivity (RSFC). While there was no overall difference in Glx intensity between young and aging adults, we identified a positive correlation between delayed word-list recall and Glx, bilaterally in older adults, but not in young adults. Collapsed across age, we also discovered a negative relationship between Glx intensity and RSFC between the anterior hippocampus and regions in the subcallosal gyrus, replicating a recent finding by Wagner et al., (2016). These findings demonstrate the possibly utility of Glx in identifying age-related changes in the brain and behavior and provide encouragement that MRS can be useful in predicting age-related decline before any physical abnormalities are present.

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“…A recent report for our group demonstrated that GH induced an increase in dendritic length in layer 3 of the PFC and CA1 of the dorsal hippocampus (Olivarez‐Hernández et al, ). In addition, cognitive functions decline during aging and several reports have demonstrated an increase in the extracellular levels of glutamate, that in high levels may induce neurotoxicity (Brewer, ; Choi et al, ; Zoia et al, ) and also alter mitochondrial function (Avila et al, ; Choi et al, ; Plaitakis, Zaganas, & Spanaki, ), which results in reduced dendritic length (Jia et al, ). In addition, reduced glutamatergic input to layer 5 of the PFC also reduced dendritic length of the pyramidal neurons (Kelly, Huang, Meltzer, & Martina, ).…”

Section: Discussionmentioning

confidence: 99%

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Flores-Vivaldo

Camacho-Ábrego

Picazo

et al. 2019

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Pregnancy is a complex process, involving a number of hormones and trophic factors, many of which are formed in the placenta. Several of these trophic factors have an effect at the neuronal level, such as BDNF. Consequently, recent reports have shown that exposure to these hormones (estrogen and progesterone) and trophic factors such as BDNF exert a neuroprotective effect. Here, we study the effect of the number of pregnancies on dendritic morphology of aged female rats (18 months of age). Rats of the 18‐month‐old Sprague Dawley strain with zero, one, two, and three gestations were evaluated for locomotor activity, and Golgi–Cox stain was performed to evaluate the dendritic morphology parameters, the number of dendritic spines, total dendritic length, and branching order number. Adult nulliparous rats (3 months of age) were used as another control group. Adult nulliparous and aging rats with two pregnancies showed an increase in locomotor activity. Adult nulliparous showed an increase in the dendritic spine number compared to old nulliparous rats in both layers of the PFC, the DG, and NAcc. Old rats with two and three pregnancies also showed an increase in the number of dendritic spines compared to old nulliparous rats in layers 3 and 5 of the PFC and in the CA1. Aging animals with one pregnancy also showed an increase in dendritic length compared to old nulliparous rats in the CA1. Our results clearly suggest that two and three pregnancies increase the dendritic spines number in the PFC and CA1 of aged female rats.

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Metabolism Changes During Aging in the Hippocampus and Striatum of Glud1 (Glutamate Dehydrogenase 1) Transgenic Mice

Cited by 13 publications

References 72 publications

Effects of Ethanol Exposure on the Neurochemical Profile of a Transgenic Mouse Model with Enhanced Glutamate Release Using In Vivo 1H MRS

Effects of Ethanol Exposure on the Neurochemical Profile of a Transgenic Mouse Model with Enhanced Glutamate Release Using In Vivo 1H MRS

3T hippocampal glutamate-glutamine complex reflects verbal memory decline in aging

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

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