Impaired learning and memory in Pitx3 deficient aphakia mice: A genetic model for striatum-dependent cognitive symptoms in Parkinson's disease
Section snippets
Animals
Adult male ak mice used in this study were originally from The Jackson Laboratory (Bar Harbor, ME) (strain B6_C57BLKS-ak; JR942). They were outcrossed several times to C57BL/6 mice and maintained in the C57BL/6 background. Several breeding pairs were transferred, expanded, and maintained at the Animal Care Facility at McLean Hospital. Wild-type (wt) C57BL/6 mice were obtained from The Jackson Laboratory and used as control. Mice homozygous for retinal degeneration 1 (rd1 or Pde6brd1) mutation (
Results
The rotatord is used to measure balance, coordination, motor function and motor learning. Lesions of the striatum and cerebellum can impair rotarod performance and/or learning. As shown in Fig. 1 performance on the rotarod was similar across all three groups on day 1 which suggests lack of gross motor impairment in ak mice. Whereas wt and rd1 mice improved their performance over the next 2 days the learning curve for ak mice was nearly flat (Fig. 1, Top Panel). Analysis of the learning curves
Discussion
The major finding reported here is that deficiency of the transcription factor Pitx3 in mice results in striatum-dependent cognitive impairments. Importantly, the type of impairment we have observed in ak mice overlaps categorically with that observed in human PD since PD has been shown to involve both procedural (Allain et al., 1995, Thomas et al., 1996) and associative learning impairments (Vriezen and Moscovitch, 1990, Sprengelmeyer et al., 1995). These novel findings are interesting for
Acknowledgments
This work was supported by NIH grants MH48866 and DC006501, and an International Grant from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea. The authors are grateful to Jessie Kang for her excellent technical assistance.
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Animal models for preclinical Parkinson's research: An update and critical appraisal
2020, Progress in Brain ResearchPitx3 deficient mice as a genetic animal model of co-morbid depressive disorder and parkinsonism
2014, Brain ResearchCitation Excerpt :Measurement and diagnosis of depressive disorders in PD is difficult due to the considerable overlap between the symptoms and signs of the two illnesses (Schrag, 2006; McDonald et al., 2003). As we mentioned in a previous study (Ardayfio et al., 2008), the increased prevalence rate of non-motor symptoms, such as depressive disorders, in PD patients may be caused by biochemical and behavioral abnormalities in coping with stress (Charlett et al., 1998; King et al., 1997). Stress may play a critical role in the development of PD related and other depressive disorders (Hemmerle et al., 2012).
Molecular layer heterotopia of the cerebellar vermis in mutant and transgenic mouse models on a C57BL/6 background
2013, Brain Research BulletinCitation Excerpt :Aphakia mice have served as a valuable tool in the study of ocular development as Pitx3 plays an important role in lens formation (Rieger et al., 2001; Medina-Martinez et al., 2009). In addition, because of reports linking Pitx3 mutations in humans with Parkinson's disease (PD; Yu et al., 2011; Gui et al., 2012; Guo et al., 2011) and because of the loss of dopaminergic neurons of the substantia nigra that is observed in aphakia mice (Nunes et al., 2003; Hwang et al., 2003), these mice have been used as a model of PD (Hwang et al., 2005; Ding et al., 2007; Espadas et al., 2012; Ardayfio et al., 2008). In light of the fact that the cerebellum plays an important role in balance, posture, gait, sensory-motor function, and motor learning, our findings of MLH in aphakia mice urge caution when using these mice in behavioral and/or physiological studies where cerebellar function has been implicated.
Effects of intrastriatal botulinum neurotoxin A on the behavior of Wistar rats
2012, Behavioural Brain ResearchCitation Excerpt :A great promise of this approach is to avoid the serious side-effects of systemically administered anti-cholinergics reflected by the anti-cholinergic syndrome [9]. However, the striatum is – beside the hippocampus and the prefrontal cortex – known to be a crucial structure for learning and memory, especially for implicit procedural learning [10–15]. For example, Prado-Alcalá et al. [16] mentioned that lesions, temporal inactivation, electrical stimulation and administration of drugs that antagonize synaptic activity in the striatum lead to significant deficits in memory, and interruption of dopaminergic, GABAergic and cholinergic activity in discrete areas of the striatum is sufficient to disrupt cognitive functions.
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