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Cellular distribution of interleukin-1alpha-immunoreactivity after MPTP intoxication in mice
Guillaume Hébert1, Rozenn Mingam, Josette Arsaut
1INSERM U394, Neurobiologie Intégrative, Institut François Magendie, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
Abstract:
In young rodents, peripheral injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) results in a dopaminergic nigrostriatal denervation (during the first week after injection), followed by a spontaneous dopaminergic reinnervation. Sprouting from residual neurons has been proposed to account for this event. It has been shown that an inflammatory process takes place during striatal dopaminergic denervation but its consequences remain controversial. Some clues notably indicate that interleukin (IL)-1alpha may participate in MPTP-induced inflammation and promote recovery. We therefore studied the immunohistochemical localization of IL-1alpha expression in the striatum and ventral mesencephalon at different times (1, 3, 6, 16, and 30 days) after MPTP injection in mice. IL-1alpha-immunoreactivity (ir) was observed in striatum, substantia nigra pars compacta, and ventral tegmental area. Apart from a few localization in mesencephalic activated microglia, IL-1alpha was almost exclusively found in activated astrocytes. However, in the striatal parenchyma, another component of IL-1alpha-ir colocalized with tyrosine hydroxylase (TH)-ir, a marker for dopaminergic neurons. Moreover, some parenchymal TH-positive axons were also found to express the growth cone-associated protein (GAP)-43, a marker for axonal growth cones. In the striatum, IL-1alpha-ir was also detected in a non-astrocytic perivascular component, with a distribution similar to GAP-43-ir. IL-1alpha could thus directly or indirectly influence striatal reorganization after MPTP.
Insights
Interleukin-1alpha (IL-1alpha) is found in activated astrocytes and dopaminergic neurons following MPTP-induced brain injury. This suggests IL-1alpha may play a role in the recovery and reinnervation of dopaminergic pathways.
Area of Science:
- Neuroscience
- Neuroinflammation
- Neuroregeneration
Background:
- N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes dopaminergic neurodegeneration in rodents, followed by spontaneous reinnervation.
- Inflammation is implicated in MPTP-induced denervation, with interleukin-1alpha (IL-1alpha) potentially promoting recovery.
Purpose of the Study:
- To investigate the immunohistochemical localization of IL-1alpha in the mouse striatum and ventral mesencephalon after MPTP injection.
- To explore the potential role of IL-1alpha in the neuroinflammatory and neuroregenerative processes following MPTP exposure.
Main Methods:
- Mice were injected with MPTP, and brain tissue was collected at multiple time points (1, 3, 6, 16, 30 days).
- Immunohistochemistry was used to detect IL-1alpha, tyrosine hydroxylase (TH)-ir, and growth cone-associated protein (GAP)-43 expression.
Main Results:
- IL-1alpha immunoreactivity was observed in the striatum, substantia nigra, and ventral tegmental area, primarily in activated astrocytes.
- A subset of IL-1alpha immunoreactivity colocalized with TH-ir in the striatal parenchyma, indicating expression in dopaminergic neurons or their processes.
- IL-1alpha was also found in a perivascular component in the striatum, mirroring the distribution of GAP-43-ir, a marker for axonal growth cones.
Conclusions:
- IL-1alpha is expressed in activated astrocytes and potentially within dopaminergic neurons and their growth cones after MPTP treatment.
- These findings suggest that IL-1alpha may directly or indirectly influence striatal reorganization and dopaminergic reinnervation following neurotoxic injury.
