Ambra1 Shapes Hippocampal Inhibition/Excitation Balance: Role in Neurodevelopmental Disorders

Nobili, Annalisa; Krashia, Paraskevi; Cordella, Alberto; Barbera, Livia La; Dell’Acqua, Maria Concetta; Caruso, Angela; Pignataro, Annabella; Marino, Ramona; Sciarra, Francesca; Biamonte, Filippo; Scattoni, María Luisa; Ammassari–Teule, Martine; Cecconi, Francesco; Berretta, Nicola; Keller, Flavio; Mercuri, Nicola Biagio; D’Amelio, Marcello

doi:10.1007/s12035-018-0911-5

Cited by 26 publications

(32 citation statements)

References 72 publications

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“…The brains were removed and postfixed in paraformaldehyde at 4°C and then immersed in 30% sucrose solution at 4°C until sinking. The brains were then cut into 30-μm-thick coronal sections using a freezing microtome, to be used for immunohistochemistry and immunofluorescence 76,77 .…”

Section: Rotarod Testmentioning

confidence: 99%

Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease

et al. 2019

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Neuroinflammation is one of the hallmarks of Parkinson’s disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD – to modulate disease progression – still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.

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Section: Rotarod Testmentioning

confidence: 99%

Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease

et al. 2019

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“…Hippocampal tissues were homogenized in lysis buffer containing (in mM) 320 sucrose, 50 NaCl, 50 Tris-HCl pH 7.5, 1% Triton X-100, 1 sodium orthovanadate, 5 β-glycerophosphate, 5 NaF and protease inhibitor cocktail, incubated on ice for 30 min and centrifuged at 15,000 g for 10 min [152]. The total protein content of the supernatant was determined by the Bradford method.…”

Section: Total Protein Extractionmentioning

confidence: 99%

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

Cutuli

Landolfo

Decandia

et al. 2020

IJMS

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As major components of neuronal membranes, omega-3 polyunsaturated fatty acids (n-3 PUFA) exhibit a wide range of regulatory functions. Recent human and animal studies indicate that n-3 PUFA may exert beneficial effects on aging processes. Here we analyzed the neuroprotective influence of n-3 PUFA supplementation on behavioral deficits, hippocampal neurogenesis, volume loss, and astrogliosis in aged mice that underwent a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valid model to mimic a key component of the cognitive deficits associated with dementia. Aged mice were supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks and then cholinergically depleted with mu-p75-saporin immunotoxin. Two weeks after lesioning, mice were behaviorally tested to assess anxious, motivational, social, mnesic, and depressive-like behaviors. Subsequently, morphological and biochemical analyses were performed. In lesioned aged mice the n-3 PUFA pre-treatment preserved explorative skills and associative retention memory, enhanced neurogenesis in the dentate gyrus, and reduced volume and VAChT levels loss as well as astrogliosis in hippocampus. The present findings demonstrating that n-3 PUFA supplementation before cholinergic depletion can counteract behavioral deficits and hippocampal neurodegeneration in aged mice advance a low-cost, non-invasive preventive tool to enhance life quality during aging.

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“…Moreover, both spontaneous and evoked PV-mediated inhibitory currents are increased in L2/3 ACC pyramidal neurons of PV-Lmo4KO mice. Although the present study focused on PV neuron function in the ACC, PV neurons in other brain regions including cerebellum 4 and hippocampus 45 , could also contribute to ASD-like behavior deficits in PV-Lmo4KO mice. Whether compensatory changes in SST-mediated inhibitory inputs are specific to the ACC or also occur in other brain regions is an important question for future studies.…”

Section: Discussionmentioning

confidence: 99%

Hyperactivated PTP1B phosphatase in parvalbumin neurons alters anterior cingulate inhibitory circuits and induces autism-like behaviors

et al. 2020

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Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulty filtering information. Inhibitory interneurons filter information at pyramidal neurons of the anterior cingulate cortex (ACC), an integration hub for higher-order thalamic inputs important for social interaction. Humans with deletions including LMO4, an endogenous inhibitor of PTP1B, display intellectual disabilities and occasionally autism. PV-Lmo4KO mice ablate Lmo4 in PV interneurons and display ASD-like repetitive behaviors and social interaction deficits. Surprisingly, increased PV neuron-mediated peri-somatic feedforward inhibition to the pyramidal neurons causes a compensatory reduction in (somatostatin neuron-mediated) dendritic inhibition. These homeostatic changes increase filtering of mediodorsalthalamocortical inputs but reduce filtering of cortico-cortical inputs and narrow the range of stimuli ACC pyramidal neurons can distinguish. Simultaneous ablation of PTP1B in PV-Lmo4KO neurons prevents these deficits, indicating that PTP1B activation in PV interneurons contributes to ASD-like characteristics and homeostatic maladaptation of inhibitory circuits may contribute to deficient information filtering in ASD.

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Ambra1 Shapes Hippocampal Inhibition/Excitation Balance: Role in Neurodevelopmental Disorders

Cited by 26 publications

References 72 publications

Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease

Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

Hyperactivated PTP1B phosphatase in parvalbumin neurons alters anterior cingulate inhibitory circuits and induces autism-like behaviors

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