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The 6-hydroxydopamine (6-OHDA) neurotoxic lesion of the midbrain dopamine (DA) system is one of the most widely used techniques for modelling Parkinson's disease in rodents. The majority of studies using this approach, however, largely limit their analysis to lesioning acutely, and looking at behavioural deficits and the number of surviving tyrosine(More)
The specification and differentiation of dentate gyrus granule neurons in the hippocampus require temporally and spatially coordinated actions of both intrinsic and extrinsic molecules. The basic helix-loop-helix transcription factor Neurogenin2 (Ngn2) and NeuroD1 are key regulators in these processes. Based on existing classification, we analyzed the(More)
The maintained expression of transcription factors throughout the development of mesodiencephalic dopaminergic (mDA) neurons suggests multiple roles at various stages in development. Two members of the forkhead/winged helix transcription factor family, Foxa1 and Foxa2, have been recently shown to have an important influence in the early development of mDA(More)
Midbrain dopaminergic neurons are highly heterogeneous. They differ in their connectivity and firing patterns and, therefore, in their functional properties. The molecular underpinnings of this heterogeneity are largely unknown, and there is a paucity of markers that distinguish these functional subsets. In this paper, we report the identification and(More)
Progress in Parkinson's disease (PD) research has been hampered by the lack of an appropriate model which exhibits the core pathology seen in the human brain. Recent advances in deriving cells with neuronal phenotypes from patients with neurodegenerative disorders through cellular reprogramming offer a unique tool for disease modelling and may help shed(More)
Huntington's disease (HD) is an incurable, inherited, progressive neurodegenerative disorder that is defined by a combination of motor, cognitive and psychiatric features. Pre-clinical and clinical studies have demonstrated an important role for the dopamine (DA) system in HD with dopaminergic dysfunction at the level of both DA release and DA receptors. It(More)
In vivo application of viral vectors for gene transfer is a commonly used tool in anatomical and functional studies, as well as in development of neuroprotective and restorative strategies for therapy. Although the most common route of administration is via direct injection into the brain parenchyma in adult animals, a number of short-term studies have been(More)
Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is(More)
Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic delivery to the neonatal rat and minipig striatum. The(More)
Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1) is commonly associated with glutamatergic neuron development. In this study, we utilized ND1(More)