Abstract
This study analyzed gender differences in the progressive dopamine (DA) deficiency phenotype in the MitoPark (MP) mouse model of Parkinson’s disease (PD) with progressive loss of DA release and reuptake in midbrain DA pathways. We found that the progressive loss of these DA presynaptic parameters begins significantly earlier in male than female MP mice. This was correlated with behavioral gender differences of both forced and spontaneous motor behavior. The degeneration of the nigrostriatal DA system in MP mice is earlier and more marked than that of the mesolimbic DA system, with male MP mice again being more strongly affected than female MP mice. After ovariectomy, DA presynaptic and behavioral changes in female mice become very similar to those of male animals. Our results suggest that estrogen, either directly or indirectly, is neuroprotective in the midbrain DA system. Our results are compatible with epidemiological data on incidence and symptom progression in PD, showing that men are more strongly affected than women at early ages.
Highlights
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease with a broad spectrum of motor and non-motor features resulting from progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc) [1,2]
We found that both tonic and phasic release differed significantly between male and female MP mice at nine and 10 weeks of age (Figure 1c,d, p < 0.01)
The DA release in brain slices from male MP mice started to decline at seven weeks of age, while release in brain slices from female MP mice seemed to have a later decline at 10 weeks
Summary
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease with a broad spectrum of motor and non-motor features resulting from progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc) [1,2]. In further support for a “mitochondrial hypothesis” for PD pathophysiology, Bender et al [16] reported higher levels of mitochondrial DNA deletions in nigral neurons from PD patients. Both Bender et al [16] and Kraytsberg et al [17] reported higher levels of mitochondrial DNA deletions in nigral neurons in aged humans with sharp elevations starting shortly before age 70. This correlates with age being a known major risk factor for PD. A better understanding of the progressive cellular events that precede the appearance of behavioral symptoms will be critical for the early diagnosis of PD and development of more effective treatment strategies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
