Age-Related Differences in the in vitro Rat Hippocampus

Dunwiddie, Thomas V.

doi:10.1159/000112753

Cited by 41 publications

(3 citation statements)

References 9 publications

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“…Inputs from the entorhinal cortex and the perirhinal cortex indicate that complex object relations are integrated in the hippocampus, where their representations are preserved [24]. Any decline in oxygen delivery has significant effects on the hippocampus and memory function [25][26][27]. Accordingly, episodic memory is not a steady trait and is very sensitive to environmental and/or physiological changes [28,29].…”

Section: Discussionmentioning

confidence: 99%

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals

et al. 2020

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Cognition is a crucial element of human functionality. Like any other physical capability, cognition is both enabled and limited by tissue biology. The aim of this study was to investigate whether oxygen is a rate-limiting factor for any of the main cognitive domains in healthy young individuals. Fifty-six subjects were randomly assigned to either increased oxygen supply using hyperbaric oxygen (two atmospheres of 100% oxygen) or to a “sham” treatment (a simulation of increased pressure in a chamber with normal air). While in the chamber, participants went through a battery of tests evaluating the major cognitive domains including information processing speed, episodic memory, working memory, cognitive flexibility, and attention. The results demonstrated that from all evaluated cognitive domains, a statistically significant improvement was found in the episodic memory of the hyper-oxygenized group. The hyper-oxygenized group demonstrated a better learning curve and a higher resilience to interference. To conclude, oxygen delivery is a rate-limiting factor for memory function even in healthy young individuals under normal conditions. Understanding the biological limitations of our cognitive functions is important for future development of interventional tools that can be used in daily clinical practice.

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Section: Discussionmentioning

confidence: 99%

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals

et al. 2020

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“…At earlier stages of development, the picture appears to be different. In vitro experiments have shown an excitatory action of GABA at early stages of development in kittens (Schwartzkroin and Altschuler, 1977), rabbits (Mueller et al, 1983), and rats (Dunwiddie, 1981; Harris and Teyler, 1983; Mueller et al, 1984; Ben-Ari et al, 1989) in a large number of subsequent studies (for review, Ben-Ari et al, 2007). Experiments performed in rodent brain slices indicated that the switch from the excitatory to inhibitory action of GABA takes place during the second postnatal week (P12–P13; Ben-Ari et al, 2007).…”

Section: The Concept Of Excitatory Gaba In the Immature Brainmentioning

confidence: 99%

Excitatory GABA: How a Correct Observation May Turn Out to be an Experimental Artifact

Bregestovski¹,

Bernard²

2012

Front. Pharmacol.

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The concept of the excitatory action of GABA during early development is based on data obtained mainly in brain slice recordings. However, in vivo measurements as well as observations made in intact hippocampal preparations indicate that GABA is in fact inhibitory in rodents at early neonatal stages. The apparent excitatory action of GABA seems to stem from cellular injury due to the slicing procedure, which leads to accumulation of intracellular Cl− in injured neurons. This procedural artifact was shown to be attenuated through various manipulations such as addition of energy substrates more relevant to the in vivo situation. These observations question the very concept of excitatory GABA in immature neuronal networks.

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“…In addition to functioning during pathological hypoxia, HIF1/2 has been described to regulate embryonic development, 27 as well as neural stem cell survival and differentiation 93 , 94 during development. To determine if HIF-1α or HIF-2α KOs resulted in any neurodevelopmental delay that may affect performance on behavioral tests, we performed behavioral phenotyping at baseline (no prior shock or hypoxic stimuli) by measuring performance in the following three tests: OF, RR, and PA.…”

Section: Resultsmentioning

confidence: 99%

Astrocyte HIF-2α supports learning in a passive avoidance paradigm under hypoxic stress

Leiton

Chen

Cutrone

et al. 2018

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BackgroundThe brain is extensively vascularized, useŝ20% of the body’s oxygen, and is highly sensitive to changes in oxygen. While synaptic plasticity and memory are impaired in healthy individuals by exposure to mild hypoxia, aged individuals appear to be even more sensitive. Aging is associated with progressive failure in pulmonary and cardiovascular systems, exposing the aged to both chronic and superimposed acute hypoxia. The HIF proteins, the “master regulators” of the cellular response to hypoxia, are robustly expressed in neurons and astrocytes. Astrocytes support neurons and synaptic plasticity via complex metabolic and trophic mechanisms. The activity of HIF proteins in the brain is diminished with aging, and the increased exposure to chronic and acute hypoxia with aging combined with diminished HIF activity may impair synaptic plasticity.PurposeHerein, we test the hypothesis that astrocyte HIF supports synaptic plasticity and learning upon hypoxia.Materials and MethodsAn Astrocyte-specific HIF loss-of-function model was employed, where knock-out of HIF-1α or HIF-2α in GFAP expressing cells was accomplished by cre-mediated recombination. Animals were tested for behavioral (open field and rotarod), learning (passive avoidance paradigm), and electrophysiological (long term potentiation) responses to mild hypoxic challenge.ResultsIn an astrocyte-specific HIF loss-of-function model followed by mild hypoxia, we identified that the depletion of HIF-2α resulted in an impaired passive avoidance learning performance. This was accompanied by an attenuated response to induction in long-term potentiation (LTP), suggesting that the hippocampal circuitry was perturbed upon hypoxic exposure following HIF-2α loss in astrocytes, and not due to hippocampal cell death. We investigated HIF-regulated trophic and metabolic target genes and found that they were not regulated by HIF-2α, suggesting that these specific targets may not be involved in mediating the phenotypes observed.ConclusionTogether, these results point to a role for HIF-2α in the astrocyte’s regulatory role in synaptic plasticity and learning under hypoxia and suggest that even mild, acute hypoxic challenges can impair cognitive performance in the aged population who harbor impaired HIF function.

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Age-Related Differences in the in vitro Rat Hippocampus

Cited by 41 publications

References 9 publications

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals

Excitatory GABA: How a Correct Observation May Turn Out to be an Experimental Artifact

Astrocyte HIF-2α supports learning in a passive avoidance paradigm under hypoxic stress

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Age-Related Differences in the in vitro Rat Hippocampus

Cited by 41 publications

References 9 publications

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals

Excitatory GABA: How a Correct Observation May Turn Out to be an Experimental Artifact

Astrocyte HIF-2&alpha; supports learning in a passive avoidance paradigm under hypoxic stress

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Astrocyte HIF-2α supports learning in a passive avoidance paradigm under hypoxic stress