Exposure to prolonged controllable or uncontrollable stress affects GABAergic function in sub-regions of the hippocampus and the amygdala

Hadad-Ophir, Osnat; Ardi, Ziv; Brande-Eilat, Noa; Kehat, Orli; Anunu, Rachel; Richter‐Levin, Gal

doi:10.1016/j.nlm.2016.06.009

Cited by 14 publications

(8 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with that, we have recently demonstrated that activation of NPY-positive interneurons in the dDG, but not vDG provides resilience, whereas activation of CCK-interneurons in the vDG, but not dDG relates to vulnerability of rats following JVS ( Regev-Tsur et al, 2020 ). These findings are further supported by a previous report showing that uncontrollable stress causes elevation of GAD65 mRNA levels only in dDG but not vDG ( Hadad-Ophir et al, 2017 ). Thus, the dDG, which responds differently to various stressors, seems to integrate emotional and cognitive aspects of an experience and share that data with the hippocampus proper, as well as with a network of brain regions such as the amygdala and prefrontal cortex ( Fa et al, 2014 ).…”

Section: Discussionsupporting

confidence: 90%

Reducing glutamic acid decarboxylase in the dorsal dentate gyrus attenuates juvenile stress induced emotional and cognitive deficits

Tripathi

Demiray

Kliche

et al. 2021

Neurobiology of Stress

View full text Add to dashboard Cite

A high degree of regional, temporal and molecular specificity is evident in the regulation of GABAergic signaling in stress-responsive circuitry, hampering the use of systemic GABAergic modulators for the treatment of stress-related psychopathology. Here we investigated the effectiveness of local intervention with the GABA synthetic enzymes GAD65 and GAD67 in the dorsal dentate gyrus (dDG) vs ventral DG (vDG) to alleviate anxiety-like behavior and stress-induced symptoms in the rat. We induced shRNA-mediated knock down of either GAD65 or GAD67 with lentiviral vectors microinjected into the dDG or vDG of young adult male rats and examined anxiety behavior, learning and memory performance. Subsequently we tested whether reducing GAD65 expression in the dDG would also confer resilience against juvenile stress-induced behavioral and physiological symptoms in adulthood. While knock down of either isoform in the vDG increased anxiety levels in the open field and the elevated plus maze tests, the knock down of GAD65, but not GAD67, in the dDG conferred a significant reduction in anxiety levels. Strikingly, this manipulation also attenuated juvenile stress evoked anxiety behavior, cognitive and synaptic plasticity impairments. Local GABAergic circuitry in the DG plays an important and highly region-specific role in control of emotional behavior and stress responding. Reduction of GAD65 expression in the dDG appears to provide resilience to juvenile stress-induced emotional and cognitive deficits, opening a new direction towards addressing a significant risk factor for developing stress and trauma-related psychopathologies later in life.

show abstract

Section: Discussionsupporting

confidence: 90%

Reducing glutamic acid decarboxylase in the dorsal dentate gyrus attenuates juvenile stress induced emotional and cognitive deficits

Tripathi

Demiray

Kliche

et al. 2021

Neurobiology of Stress

View full text Add to dashboard Cite

show abstract

“…Lastly, though our perceived stress scale has been widely validated and used to examine the effects of age-related stress previously 17 , it is subjective (vs. cortisol levels) and intended to measure negative and “out of control” stress. While stress that is perceived to be out of one’s control is consistently associated with worse CNS outcomes, low levels of (self-perceived) controlled stress may actually be beneficial for challenging the immune system and brain 45,46 . Future works that appreciate the full spectrum of stress, both positive and negative, on the aging brain are highly warranted to optimally shape treatment approaches and clinical recommendations.…”

Section: Discussionmentioning

confidence: 99%

Perceived Stress is Associated with Accelerated Monocyte/Macrophage Aging Trajectories in Clinically Normal Adults

Casaletto

Staffaroni

Elahi

et al. 2018

The American Journal of Geriatric Psychiatry

View full text Add to dashboard Cite

Our data provide evidence of accelerated immune aging among individuals with high stress. Elevated macrophage cytokine trajectories mediated the effect of age on executive function only in individuals with high stress, suggesting these constructs may be more tightly linked in elevated stress contexts. Stress interventions are warranted to optimize immune aging, with possible downstream cognitive benefits among even clinically normal adults.

show abstract

“…Additionally, we randomly shuffled mean durations to enhance the perception of arbitrary stress durations in YC. Pseudo-yoking is well-established in animal designs [50,75] and more practical in group testing sessions. All other parameters (response limit in EC, shift of cue onsets in YC) were the same as in study 1.…”

Section: Stress Inductionmentioning

confidence: 99%

A Translational Paradigm to Study the Effects of Uncontrollable Stress in Humans

Meine

Schüler

Richter‐Levin

et al. 2020

IJMS

View full text Add to dashboard Cite

Theories on the aetiology of depression in humans are intimately linked to animal research on stressor controllability effects. However, explicit translations of established animal designs are lacking. In two consecutive studies, we developed a translational paradigm to study stressor controllability effects in humans. In the first study, we compared three groups of participants, one exposed to escapable stress, one yoked inescapable stress group, and a control group not exposed to stress. Although group differences indicated successful stress induction, the manipulation failed to differentiate groups according to controllability. In the second study, we employed an improved paradigm and contrasted only an escapable stress group to a yoked inescapable stress group. The final design successfully induced differential effects on self-reported perceived control, exhaustion, helplessness, and behavioural indices of adaptation to stress. The latter were examined in a new escape behaviour test which was modelled after the classic shuttle box animal paradigm. Contrary to the learned helplessness literature, exposure to uncontrollable stress led to more activity and exploration; however, these behaviours were ultimately not adaptive. We discuss the results and possible applications in light of the findings on learning and agency beliefs, inter-individual differences, and interventions aimed at improving resilience to stress-induced mental dysfunction.

show abstract

Exposure to prolonged controllable or uncontrollable stress affects GABAergic function in sub-regions of the hippocampus and the amygdala

Cited by 14 publications

References 60 publications

Reducing glutamic acid decarboxylase in the dorsal dentate gyrus attenuates juvenile stress induced emotional and cognitive deficits

Reducing glutamic acid decarboxylase in the dorsal dentate gyrus attenuates juvenile stress induced emotional and cognitive deficits

Perceived Stress is Associated with Accelerated Monocyte/Macrophage Aging Trajectories in Clinically Normal Adults

A Translational Paradigm to Study the Effects of Uncontrollable Stress in Humans

Contact Info

Product

Resources

About