Parkinson's disease (PD) is characterized by selective death of the substantia nigra dopaminergic neurons, and previously we have shown that aphakia mice, which harbor spontaneous Pitx3 gene mutation, show specific degeneration of the substantia nigra dopaminergic neurons accompanied by behavioral deficits that is reversed by L-DOPA treatment or transplantation of dopaminergic neural precursors. Here, we describe transplantation of dopaminergic neural precursors to a mouse model of PD, an aphakia mouse, followed by behavioral analyses of transplanted mice.
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http://dx.doi.org/10.1007/978-1-4939-1453-1_23 | DOI Listing |
Front Cell Dev Biol
October 2024
Laboratory of Transcriptional Regulation, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.
Landmark discovery of eye defects caused by Pax6 gene mutations in humans, rodents, and even fruit flies combined with Pax6 gene expression studies in various phyla, led to the master control gene hypothesis postulating that the gene is required almost universally for animal visual system development. However, this assumption has not been broadly tested in genetically trackable organisms such as vertebrates. Here, to determine the functional role of the fish orthologue of mammalian Pax6 in eye development we analyzed mutants in medaka Pax6.
View Article and Find Full Text PDFNeurobiol Dis
August 2022
Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. Electronic address:
Parkinson's disease (PD) is characterized by the selective death of substantia nigra pars compacta (SNpc) dopaminergic neurons and includes both motor and non-motor symptoms. While numerous models exist for the study of typical PD motor deficits, fewer exist for non-motor symptoms. Previous studies have shown that a Pitx3 mouse model (aphakia or ak mouse) has specific developmental failure of the dopaminergic neuron population in the SNpc and that it can be used for the study of PD-related gross motor dysfunction as well as cognitive functional deficits.
View Article and Find Full Text PDFCell Rep
January 2022
Department of Biological Sciences, California State Polytechnic University Pomona, Pomona, CA 91768, USA. Electronic address:
Pitx3 mice lack a functioning retina and develop fewer than 10% of dopamine neurons in the substantia nigra. Del Río-Martín et al. (2019) reported that entrainment of circadian rhythms to daily light-dark (LD) cycles is absent in these mice, and that rhythms of locomotor activity, energy expenditure, and other metabolic variables are disrupted with food available ad libitum and fail to entrain to a daily feeding.
View Article and Find Full Text PDFCell Rep
January 2022
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas /Universidad Autónoma de Madrid, Calle Arturo Duperier 4, 28029 Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM, Madrid, Spain. Electronic address:
Metabolic homeostasis is under circadian regulation to adapt energy requirements to light-dark cycles. Feeding cycles are regulated by photic stimuli reaching the suprachiasmatic nucleus via retinohypothalamic axons and by nutritional information involving dopaminergic neurotransmission. Previously, we reported that Pitx3-mutant Aphakia mice with altered development of the retinohypothalamic tract and the dopaminergic neurons projecting to the striatum, are resistant to locomotor and metabolic entrainment by time-restricted feeding.
View Article and Find Full Text PDFCommun Biol
September 2021
Department of Molecular, Cellular and Biomedical Sciences, CUNY School of Medicine at City College of New York, City University of New York, New York, NY, USA.
L-Dopa induced dyskinesia (LID) is a debilitating side effect of dopamine replacement therapy for Parkinson's Disease. The mechanistic underpinnings of LID remain obscure. Here we report that diminished sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons facilitates the formation and expression of LID.
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