ArticleEMBO molecular medicine2015
Lack of kinase-independent activity of PI3Kγ in locus coeruleus induces ADHD symptoms through increased CREB signaling.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Neurodevelopmental outcomes relevant to autism in juvenile mice exposed to PCB 11 in the maternal diet throughout gestation and lactation.Frontiers in toxicology · 2026Article
- Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.iScience · 2025Article
- Genetic Variants Linked to Dyslexia Co-Morbid ADHD: A Case Study of a Pakistani Outpatient.Journal of population therapeutics and clinical pharmacology = Journal de la therapeutique des populations et de la pharmacologie clinique · 2024Article
- An updated review on animal models to study attention-deficit hyperactivity disorder.Translational psychiatry · 2024Review
- Serotonin sensing by microglia conditions the proper development of neuronal circuits and of social and adaptive skills.Molecular psychiatry · 2023Article
- Distractibility and impulsivity neural states are distinct from selective attention and modulate the implementation of spatial attention.Nature communications · 2022Article
- Neuroimmune axis of cardiovascular control: mechanisms and therapeutic implications.Nature reviews. Cardiology · 2022Review
- Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder.Current neuropharmacology · 2022Review
- Nutrigenomic Studies on the Ameliorative Effect of Enzyme-Digested Phycocyanin in Alzheimer's Disease Model Mice.Nutrients · 2021Article
- Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior.Molecular psychiatry · 2021Article
- Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- The developmental neurotoxicity of legacy vs. contemporary polychlorinated biphenyls (PCBs): similarities and differences.Environmental science and pollution research international · 2020Review
- Evidence Implicating Non-Dioxin-Like Congeners as the Key Mediators of Polychlorinated Biphenyl (PCB) Developmental Neurotoxicity.International journal of molecular sciences · 2020Review
- Induction of Neuronal PI3Kγ Contributes to Endoplasmic Reticulum Stress and Long-Term Functional Impairment in a Murine Model of Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Article
- Function, Regulation and Biological Roles of PI3Kγ Variants.Biomolecules · 2019Review
- PI3Kinases in Diabetes Mellitus and Its Related Complications.International journal of molecular sciences · 2018Review
- 3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism.Archives of toxicology · 2018Article
- Differential Behavioral and Biochemical Responses to Caffeine in Male and Female Rats from a Validated Model of Attention Deficit and Hyperactivity Disorder.Molecular neurobiology · 2018Article
- Melatonin inhibits attention-deficit/hyperactivity disorder caused by atopic dermatitis-induced psychological stress in an NC/Nga atopic-like mouse model.Scientific reports · 2018Article
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10 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Although PI3Kγ has been extensively investigated in inflammatory and cardiovascular diseases, the exploration of its functions in the brain is just at dawning. It is known that PI3Kγ is present in neurons and that the lack of PI3Kγ in mice leads to impaired synaptic plasticity, suggestive of a role in behavioral flexibility. Several neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), involve an impairment of behavioral flexibility. Here, we found a previously unreported expression of PI3Kγ throughout the noradrenergic neurons of the locus coeruleus (LC) in the brainstem, serving as a mechanism that regulates its activity of control on attention, locomotion and sociality. In particular, we show an unprecedented phenotype of PI3Kγ KO mice resembling ADHD symptoms. PI3Kγ KO mice exhibit deficits in the attentive and mnemonic domains, typical hyperactivity, as well as social dysfunctions. Moreover, we demonstrate that the ADHD phenotype depends on a dysregulation of CREB signaling exerted by a kinase-independent PI3Kγ-PDE4D interaction in the noradrenergic neurons of the locus coeruleus, thus uncovering new tools for mechanistic and therapeutic research in ADHD.
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