ArticleHuman molecular genetics2016
Neurodevelopmental alterations and seizures developed by mouse model of infantile hypophosphatasia are associated with purinergic signalling deregulation.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- SETDB1 modulates neuroinflammation in the mouse cortex by regulating neuronal P2rx7 expression.Molecular psychiatry · 2026Article
- Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- ENPP1 inhibition as a therapeutic approach for later-onset hypophosphatasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Deficiency of Tissue Nonspecific Alkaline Phosphatase Dysregulates Microglial Morphology and Function in a Mouse Model of Infantile Hypophosphatasia.Journal of neurochemistry · 2026Article
- Establishment and behavioural characterization of a novel constitutive P2X7 receptor knockout mouse line.Purinergic signalling · 2025Article
- Diagnosis and Treatment of Hypophosphatasia.Calcified tissue international · 2025Review
- Tracking Neural Migration in Dentate Gyrus Using Thymidine Analogs.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Review
- The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion.Journal of endocrinological investigation · 2024Article
- P2X7 purinergic receptor modulates dentate gyrus excitatory neurotransmission and alleviates schizophrenia-like symptoms in mouse.iScience · 2023Article
- TNAP and P2X7R: New Plasma Biomarkers for Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Altered Purinergic Signaling in Neurodevelopmental Disorders: Focus on P2 Receptors.Biomolecules · 2023Review
- Animal Models for the Investigation of P2X7 Receptors.International journal of molecular sciences · 2023Review
- The P2X7 Receptor as a Mechanistic Biomarker for Epilepsy.International journal of molecular sciences · 2023Review
- Machine learning classification reveals robust morphometric biomarker of glial and neuronal arbors.Journal of neuroscience research · 2023Article
- Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor.International journal of molecular sciences · 2022Review
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
- Deletion of the Pyrophosphate Generating Enzyme ENPP1 Rescues Craniofacial Abnormalities in the TNAPFrontiers in dental medicine · 2022Article
- Studying the Role of P2X7 Receptor in Axonal Growth Using In Utero Electroporation Technique.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Analysis of P2X7-Induced Neuronal Branching.Methods in molecular biology (Clifton, N.J.) · 2022Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Hypomorphic mutations in the gene encoding the tissue-nonspecific alkaline phosphatase (TNAP) enzyme, ALPL in human or Akp2 in mice, cause hypophosphatasia (HPP), an inherited metabolic bone disease also characterized by spontaneous seizures. Initially, these seizures were attributed to the impairment of GABAergic neurotransmission caused by altered vitamin B6 (vit-B6) metabolism. However, clinical cases in human newborns and adults whose convulsions are refractory to pro-GABAergic drugs but controlled by the vit-B6 administration, suggest that other factors are involved. Here, to evaluate whether neurodevelopmental alterations are underlying the seizures associated to HPP, we performed morphological and functional characterization of postnatal homozygous TNAP null mice, a model of HPP. These analyses revealed that TNAP deficient mice present an increased proliferation of neural precursors, an altered neuronal morphology, and an augmented neuronal activity. We found that these alterations were associated with a partial downregulation of the purinergic P2X7 receptor (P2X7R). Even though deficient P2X7R mice present similar neurodevelopmental alterations, they do not develop neonatal seizures. Accordingly, we found that the additional blockage of P2X7R prevent convulsions and extend the lifespan of mice lacking TNAP. In agreement with these findings, we also found that exogenous administration of ATP or TNAP antagonists induced seizures in adult wild-type mice by activating P2X7R. Finally, our results also indicate that the anticonvulsive effects attributed to vit-B6 may be due to its capacity to block P2X7R. Altogether, these findings suggest that the purinergic signalling regulates the neurodevelopmental alteration and the neonatal seizures associated to HPP.
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