Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis
| Autor: | Ellen Bible, Michael Wong, Catherine Kielar, Charlie C. Pontikis, Shannon L. Macauley, Jonathan D. Cooper, Lucy Maddox, Mark S. Sands, Megan A. Griffey |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Batten disease
Aging Thalamus Infantile neuronal ceroid lipofuscinosis Somatosensory system Inhibitory postsynaptic potential Article lcsh:RC321-571 PPT1 Mice Interneurons Neuronal Ceroid-Lipofuscinoses Seizures medicine Animals Palmitoyl protein thioesterase Gliosis Thalamic neurodegeneration lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cerebral Cortex Mice Knockout Neurons biology Electroencephalography medicine.disease GABAergic interneurons Mice Inbred C57BL Disease Models Animal Phenotype Neurology nervous system Microscopy Fluorescence Astrocytes Thalamic Nuclei Synapses biology.protein Disease Progression GABAergic Thiolester Hydrolases Atrophy Neuroscience Neuroglia |
| Zdroj: | Neurobiology of Disease, Vol 25, Iss 1, Pp 150-162 (2007) |
| Popis: | Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1-deficient mice (Ppt1−/−) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression, but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1−/− mice, revealing the thalamus as an important early focus of INCL pathogenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|