Altered neurotransmission in the lateral amygdala in aged human apoE4 targeted replacement mice

Klein, Rebecca C.; Acheson, Shawn K.; Mace, Brian; Sullivan, Patrick M.; Moore, Scott D.

doi:10.1016/j.neurobiolaging.2014.02.019

Cited by 25 publications

(21 citation statements)

References 38 publications

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“…Post-synaptically, middle-aged APOE4 TR mice have reduced spontaneous excitatory postsynaptic currents in the amygdala [28], but increased excitatory activity at old age [38]. APOE TR mice show alterations in long-term potentiation (LTP) in different subregions of the hippocampus related to the NMDA glutamate receptor (NMDAR)-dependent signaling pathway: APOE4 TR mice show increased LTP in the mossy fibers compared to APOE2 TR mice [39], while APOE4 TR and APOE2 TR mice have reduced LTP compared to APOE3 TR mice in the dentate gyrus [40].…”

Section: Apoe Genotype Effects On the Normal Brainmentioning

confidence: 99%

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Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function

Battista¹,

Heinsinger²,

Rebeck³

2016

CAR

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APOE-ε4 is the strongest genetic risk factor for Alzheimer’s disease (AD), and is associated with an increase in the levels of amyloid deposition and an early age of onset. Recent data demonstrate that AD pathological changes occur decades before clinical symptoms, raising questions about the precise onset of the disease. Now a convergence of approaches in mice and humans has demonstrated that APOE-ε4 affects normal brain function even very early in life in the absence of gross AD pathological changes. Normal mice expressing APOE4 have task-specific spatial learning deficits, as well as reduced NMDAR-dependent signaling and structural changes to presynaptic and postsynaptic compartments in neurons, particularly in hippocampal regions. Young humans possessing APOE-ε4 are more adept than APOE-ε4 negative individuals at some behavioral tasks, and functional magnetic resonance imaging has shown that inheritance of APOE-ε4 has specific effects on medial temporal brain activities. These findings suggest that inheritance of APOE-ε4 causes life long changes to the brain that may be related to the late risk of AD. Several possible mechanisms of how APOE-ε4 could affect brain neurochemistry, structure, and function are reviewed.

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Section: Apoe Genotype Effects On the Normal Brainmentioning

confidence: 99%

“…APOE4 TR mice have higher levels of excitatory synaptic activity in amygdala neurons compared to other APOE genotypes [38]. APOE4 TR mice show an increased risk of seizures and synchronous hippocampal neurons firing, as well as a greater sensitivity to treatment with a drug to induce seizures [120].…”

Section: Mechanisms Of Effects Of Apoe Genotype Effectsmentioning

confidence: 99%

Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function

Battista¹,

Heinsinger²,

Rebeck³

2016

CAR

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“…In a study using the apolipoprotein E4 (apoE4)‐targeted replacement mouse to model AD (Wang et al, ), 1‐ or 7‐ month‐old mice expressing apoE4 displayed reduced excitatory synaptic transmission in the LA but no changes in inhibitory synaptic transmission (Klein et al, ). However, aged (18–20 months) apoE4 animals displayed significant increases in both inhibitory and excitatory synaptic transmission and an increased seizure phenotype (Hunter et al, ; Klein et al, ), suggesting that increased excitatory synaptic transmission predominates. The results indicate that it is unlikely that, in the LA, there are alterations in the subunit composition of the GABA A receptor; rather, increased excitatory transmission may be the result of alterations in the presynaptic release of GABA.…”

Section: Gabaergic Circuit Dysfunction Within the Blamentioning

confidence: 99%

“…In a study using the apolipoprotein E4 (apoE4)-targeted replacement mouse to model AD (Wang et al, 2005), 1-or 7month-old mice expressing apoE4 displayed reduced excitatory synaptic transmission in the LA but no changes in inhibitory synaptic transmission (Klein et al, 2010). However, aged (18-20 months) apoE4 animals displayed significant increases in both inhibitory and excitatory synaptic transmission and an increased seizure phenotype (Hunter et al, 2012;Klein et al, 2014), suggesting that increased excitatory synaptic transmission predominates.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…Acquired deficiencies in the GABAergic inhibitory system have been observed after traumatic brain injury (TBI; Reger et al, 2012;Almeida-Suhett et al, 2014;Depue et al, 2014;Guerriero et al, 2015) and status epilepticus (SE; Gean et al, 1989;Fritsch et al, 2009;Prager et al, 2014b). In addition, amygdala hyperexcitability resulting in anxiety has been observed in neuropsychiatric disorders, such as posttraumatic stress disorder (PTSD; Nuss, 2015;Truitt et al, 2009), as well as in neurodevelopmental disorders, including autism/fragile X syndrome (Olmos-Serrano et al, 2010;El-Ansary and Al-Ayadhi, 2014;Martin et al, 2014), and in neurodegenerative disorders, such as Alzheimer's disease (AD; Klein et al, 2014;Palop and Mucke, 2010).…”

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confidence: 99%

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The basolateral amygdala γ‐aminobutyric acidergic system in health and disease

Prager

Bergstrom

Wynn

et al. 2015

J of Neuroscience Research

145

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The brain comprises an excitatory/inhibitory neuronal network that maintains a finely tuned balance of activity critical for normal functioning. Excitatory activity in the basolateral amygdala (BLA), a brain region that plays a central role in emotion and motivational processing, is tightly regulated by a relatively small population of gamma-aminobutyric acid (GABA) inhibitory neurons. Disruption in GABAergic inhibition in the BLA can occur when there is a loss of local GABAergic interneurons, alterations in GABAA receptor activation, or dysregulation of mechanisms that modulate BLA GABAergic inhibition. Disruptions in GABAergic control of the BLA emerge during development, in aging populations, or after a trauma, ultimately resulting in hyperexcitability. BLA hyperexcitability manifests behaviorally as an increase in anxiety, emotional dysregulation, or the development of seizure activity. This article reviews the anatomy, development, and physiology of the GABAergic system in the BLA, and circuits that modulate GABAergic inhibition, including the dopaminergic, serotonergic, noradrenergic, and cholinergic systems. We highlight how alterations in various neurotransmitter receptors, including the acid sensing ion channel 1a (ASIC1a), cannabinoid receptor 1 (CB1), and glutamate receptor subtypes, expressed on BLA interneurons, modulate GABAergic transmission and how defects of these systems affects inhibitory tonus within the BLA. Finally, we discuss alterations in the BLA GABAergic system in neurodevelopmental (autism/Fragile X syndrome) and neurodegenerative (Alzheimer’s disease) diseases, and after the development of epilepsy, anxiety, and traumatic brain injury. A more complete understanding of the intrinsic excitatory/inhibitory circuit balance of the amygdala and how imbalances in inhibitory control contribute to excessive BLA excitability will guide the development of novel therapeutic approaches in neuropsychiatric diseases.

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Anxiolytic and antidepressant‐like effects of Ferulago angulata essential oil in the scopolamine rat model of Alzheimer's disease

Bağcı

Aydin

Mihășan

et al. 2015

Flavour & Fragrance J

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Ferulago angulata subsp. carduchorum (Apiaceae) is a shrub indigenous to western Iran, Turkey and Iraq. In traditional medicine, F. angulata is recommended for treating digestive pains, haemorrhoids, snake bites, ulcers and as a sedative. The present study analysed the possible anxiolytic, antidepressant and antioxidant properties of F. angulata essential oil in a scopolamine‐induced rat model of Alzheimer's disease. The anxiolytic and antidepressant‐like effects of F. angulata essential oil were studied using in vivo (elevated plus‐maze and forced swimming tests) approaches. Also, the antioxidant activity in the amygdala was assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. The scopolamine‐treated rats exhibited the following: a decrease in the percentage of the time spent and the number of entries in the open arm within the elevated plus‐maze test and a decrease of swimming time and an increase of immobility time in the forced swimming test. Inhalation of F. angulata essential oil significantly exhibited anxiolytic and antidepressant‐like effects and also antioxidant potential. Furthermore, in silico studies carried out by employing molecular docking experiments pointed to the existence of strong interactions of monoterpenes from F. angulata essential oil with anxiolytic and antidepressant effects with GABAA receptor. Our results suggest that the F. angulata essential oil inhalation ameliorates scopolamine‐induced anxiety and depression by attenuation of the oxidative stress in the rat amygdala. Copyright © 2015 John Wiley & Sons, Ltd.

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Altered neurotransmission in the lateral amygdala in aged human apoE4 targeted replacement mice

Cited by 25 publications

References 38 publications

Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function

Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function

The basolateral amygdala γ‐aminobutyric acidergic system in health and disease

Anxiolytic and antidepressant‐like effects of Ferulago angulata essential oil in the scopolamine rat model of Alzheimer's disease

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