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Alteration of corticotropin-releasing factor immunoreactivity in MPTP-treated rats
1Institute of Neuroscience, National Yang-Ming Medical College, Taipei, Taiwan, The Republic of China.
Abstract:
A decrease of corticotropin-releasing factor (CRF) concentration has been reported in patients with Parkinson's disease (PD). The present study further examined the role of CRF in an animal model of parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Results indicated that both subchronic (2 days) and chronic (7 days) MPTP treatments decreased the number of CRF immunoreactive neurons in both the paraventricular nucleus (PVN) of the hypothalamus and the central nuelcus of the amygdala (ACN). This effect lasted for almost a month after withdrawal of chronic MPTP injections. In addition, nomifensine pretreatment protected against MPTP's toxicity on DA neurons, as assessed by tyrosine hydroxylase immunoreactivity in the substantia nigra. However, the same treatment did not prevent the toxicity of MPTP on CRF neurons. Further, no significant difference was notable in the number of CRF immunoreactive neurons between normal young adult and normal middle-aged rats in both the PVN and the ACN. These results suggest that MPTP also produces a neurotoxicity on CRF neurons, and this effect is not secondary to MPTP's effect on DA neurons. Besides, altered CRF neuronal activity is involved in the process of pathological ageing, but not physiological ageing. Further, reduced CRF immunoreactivity in the PVN and ACN may imply alterations of neuroendocrine, autonomic as well as central functions caused by MPTP.
Insights
Parkinson's disease (PD) may involve decreased corticotropin-releasing factor (CRF). MPTP-induced parkinsonism in rats reduced CRF neurons, suggesting MPTP directly impacts CRF systems, not just dopamine neurons.
Area of Science:
- Neuroscience
- Endocrinology
- Pathology
Background:
- Parkinson's disease (PD) is associated with decreased corticotropin-releasing factor (CRF) concentrations.
- The role of CRF in parkinsonism requires further investigation, particularly in animal models.
Purpose of the Study:
- To investigate the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on CRF neurons in an animal model of parkinsonism.
- To determine if MPTP's neurotoxicity extends to CRF neurons independently of its effects on dopamine (DA) neurons.
Main Methods:
- MPTP was administered to rats to induce parkinsonism.
- CRF immunoreactive neurons were quantified in the paraventricular nucleus (PVN) and central nucleus of the amygdala (ACN).
- Tyrosine hydroxylase immunoreactivity was used to assess DA neuron toxicity; nomifensine was used as a neuroprotective agent.
Main Results:
- MPTP treatment significantly decreased CRF immunoreactive neurons in the PVN and ACN.
- This reduction in CRF neurons persisted for nearly a month after MPTP withdrawal.
- Nomifensine protected DA neurons but not CRF neurons from MPTP toxicity.
- No age-related changes in CRF neurons were observed in control rats.
Conclusions:
- MPTP induces neurotoxicity in CRF neurons, independent of its effects on DA neurons.
- Altered CRF neuronal activity is linked to pathological, not physiological, aging.
- Reduced CRF immunoreactivity in the PVN and ACN suggests potential neuroendocrine, autonomic, and central functional disruptions in MPTP-induced parkinsonism.
