Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque

Liao, Chenghong; Han, Qian; Ma, Yuanye; Su, Bing

doi:10.1016/j.gene.2016.05.010

Cited by 17 publications

(25 citation statements)

References 90 publications

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“…Hence the exact mechanistic connection, if any, between our observed elevated GABA and visual behavioural alterations in older adults must remain somewhat speculative. Nevertheless, our principal finding of elevated GABA in older adults receives support from a recent gene expression study of older rhesus monkeys that reported upregulation of several components of the GABAergic system in primary visual cortex 46 . Furthermore, our behavioural findings are completely consistent with previous visual perceptual studies 6 , 18 , 20 , 21 , 23 , and there are plausible neurobiological explanations for our observed relationship between GABA levels and both visual tasks.…”

Section: Discussionsupporting

confidence: 69%

Occipital GABA levels in older adults and their relationship to visual perceptual suppression

Pitchaimuthu

Carter

et al. 2017

Sci Rep

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Several studies have attributed certain visual perceptual alterations in older adults to a likely decrease in GABA (Gamma Aminobutyric Acid) concentration in visual cortex, an assumption based on findings in aged non-human primates. However, to our knowledge, there is no direct evidence for an age-related decrease in GABA concentration in human visual cortex. Here, we estimated visual cortical GABA levels and Glx (combined estimate of glutamate and glutamine) levels using magnetic resonance spectroscopy. We also measured performance for two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion and binocular rivalry. Our results show increased visual cortical GABA levels, and reduced Glx levels, in older adults. Perceptual performance differed between younger and older groups for both tasks. When subjects of all ages were combined, visual cortical GABA levels but not Glx levels correlated with perceptual performance. No relationship was found between perception and GABA levels in dorsolateral prefrontal cortex. Perceptual measures and GABA were not correlated when either age group was considered separately. Our results challenge current assumptions regarding neurobiological changes that occur within the aging human visual cortex and their association with certain age-related changes in visual perception.

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Section: Discussionsupporting

confidence: 69%

Occipital GABA levels in older adults and their relationship to visual perceptual suppression

Pitchaimuthu

Carter

et al. 2017

Sci Rep

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“…In the aging mouse barrel cortex on the other hand, age‐related decreases in the protein levels of both GAD isoforms were observed without significant changes in mRNA expression (Liguz‐Lecznar et al ., ). Loss of GAD level in interneurons was also observed in aging visual cortex and the hippocampus (Shi et al ., ; Stanley & Shetty, ; Liao et al ., ). Such results are not always accompanied by alterations in the GABA levels in aging tissue.…”

Section: Inside the Aged Gabaergic Synapsementioning

confidence: 97%

The space where aging acts: focus on the GABAergic synapse

2017

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SummaryAs it was established that aging is not associated with massive neuronal loss, as was believed in the mid‐20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging‐related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging‐related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging‐induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases.

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“…For example, Peinemann and colleagues (2001) have reported an age-related decrease in SICI, two other studies observed no age-related effects [4, 6], and two studies observed an age-related increase in SICI [5, 7]. These mixed results may be attributed to age-related changes in cortical gene expression in the GABAergic system [8]. Specifically, the dysregulation of glutamic acid decarboxylase (GAD65) protein with age, which plays an important role in GABA synthesis, may induce an increased expression of GABA receptors as a self-regulated compensatory effect in the cortex for the reduced GABA release during normal aging [8].…”

Section: Introductionmentioning

confidence: 99%

“…These mixed results may be attributed to age-related changes in cortical gene expression in the GABAergic system [8]. Specifically, the dysregulation of glutamic acid decarboxylase (GAD65) protein with age, which plays an important role in GABA synthesis, may induce an increased expression of GABA receptors as a self-regulated compensatory effect in the cortex for the reduced GABA release during normal aging [8]. In contrast, regarding age-related changes in ICF, one study has reported that older adults exhibit less ICF than younger adults [7].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the influence of age on GABAA and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG

Noda

Zomorrodi

Cash

et al. 2017

Aging

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Gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmissions in the prefrontal cortex decreases with age. Further, cognitive function mediated through the dorsolateral prefrontal cortex (DLPFC) also declines with age. Although neuroimaging studies have demonstrated decreased levels of these substances, direct neurophysiological data investigating the effect of aging in the DLPFC in human subjects is lacking. The advent of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) has allowed for the assessment of functional neurotransmission in vivo. In the present study, we examined short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in a group of older adults (> 60 yrs) to evaluate the strength of GABAA and glutamate-mediated neurotransmission in the DLPFC, compared to younger adults (18-59 yrs). Older adults showed an increase of amplitude of N100 by the SICI paradigm, while N45 amplitude was increased and N100 amplitude was decreased by ICF. Moreover, these modulations significantly correlated with age. Our findings provide evidence for age-related alterations of excitatory and inhibitory functions in the prefrontal cortex in healthy adults. Future studies may aim to explore these neurophysiological relationships in the DLPFC in pathological forms of aging that affect cortical functioning such as mild cognitive impairment and Alzheimer's disease.

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Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque

Cited by 17 publications

References 90 publications

Occipital GABA levels in older adults and their relationship to visual perceptual suppression

Occipital GABA levels in older adults and their relationship to visual perceptual suppression

The space where aging acts: focus on the GABAergic synapse

Characterization of the influence of age on GABAA and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG

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