Central serotonergic neuron deficiency in a mouse model of Zellweger syndrome
| Autor: | Denis I. Crane, Rani Sadia Rahim, Adrian Cuda Banda Meedeniya |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Neuroimmunomodulation Fluorescent Antibody Technique Apoptosis Cell Count Mice Transgenic Neuropathology Tryptophan Hydroxylase Biology Serotonergic Internal medicine Peroxisomal disorder Peroxisomes medicine Animals Gliosis Zellweger Syndrome Zellweger syndrome TPH2 General Neuroscience Neurodegeneration Brain Membrane Proteins medicine.disease Axons Disease Models Animal Endocrinology Mutation medicine.symptom Raphe nuclei Neuroscience Serotonergic Neurons |
| Zdroj: | Neuroscience. 274:229-241 |
| ISSN: | 0306-4522 |
| Popis: | Zellweger syndrome (ZS) is a severe peroxisomal disorder caused by mutations in peroxisome biogenesis, or PEX, genes. A central hallmark of ZS is abnormal neuronal migration and neurodegeneration, which manifests as widespread neurological dysfunction. The molecular basis of ZS neuropathology is not well understood. Here we present findings using a mouse model of ZS neuropathology with conditional brain inactivation of the PEX13 gene. We demonstrate that PEX13 brain mutants display changes that reflect an abnormal serotonergic system - decreased levels of tryptophan hydroxylase-2, the rate-limiting enzyme of serotonin (5-hydroxytryptamine, 5-HT) synthesis, dysmorphic 5-HT-positive neurons, abnormal distribution of 5-HT neurons, and dystrophic serotonergic axons. The raphe nuclei region of PEX13 brain mutants also display increased levels of apoptotic cells and reactive, inflammatory gliosis. Given the role of the serotonergic system in brain development and motor control, dysfunction of this system would account in part for the observed neurological changes of PEX13 brain mutants. |
| Databáze: | OpenAIRE |
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