ArticleNeurobiology of disease2011
Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice.
Article in Neurobiology of disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 186 citations in OpenAlex.
- Glial Dysfunction and Memory Impairments in a Model of Pediatric Obstructive Sleep Apnea.Glia · 2026Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- Neural stem cells of the subventricular zone: A potential stem cell pool for brain repair in Parkinson's disease.Stem cell reports · 2025Review
- Preclinical Evaluation of Novel Positron Emission Tomography (PET) Probes for Imaging Leucine-Rich Repeat Kinase 2 (LRRK2).Journal of medicinal chemistry · 2024Article
- Rbm24/Notch1 signaling regulates adult neurogenesis in the subventricular zone and mediates Parkinson-associated olfactory dysfunction.Theranostics · 2024Article
- Subthalamic nucleus but not entopeduncular nucleus deep brain stimulation enhances neurogenesis in the SVZ-olfactory bulb system of Parkinsonian rats.Frontiers in cellular neuroscience · 2024Article
- Micro-and mesoscale aspects of neurodegeneration in engineered human neural networks carrying the LRRK2 G2019S mutation.Frontiers in cellular neuroscience · 2024Article
- Beyond anosmia: olfactory dysfunction as a common denominator in neurodegenerative and neurodevelopmental disorders.Frontiers in neuroscience · 2024Review
- Efficacy of a benzothiazole-based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis.CNS neuroscience & therapeutics · 2024Article
- Leucine-rich repeat kinase 2 at a glance.Journal of cell science · 2023Article
- Amyloid precursor protein and its interacting proteins in neurodevelopment.Biochemical Society transactions · 2023Review
- Age- and Sex-Dependent Behavioral and Neurochemical Alterations in hLRRK2-G2019S BAC Mice.Biomolecules · 2022Article
- From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer's and Parkinson's diseases.Neural regeneration research · 2022Review
- Neuronal Firing and Glutamatergic Synapses in the Substantia Nigra Pars Reticulata of LRRK2-G2019S Mice.Biomolecules · 2022Article
- Changes in the Neuronal Architecture of the Hippocampus in a 6-Hydroxydopamine-Lesioned Rat Model of Parkinson Disease.International neurourology journal · 2022Article
- ERRγ Ligand Regulates Adult Neurogenesis and Depression-like Behavior in a LRRK2-G2019S-associated Young Female Mouse Model of Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement.iScience · 2022Article
- Neurogenesis in aging and age-related neurodegenerative diseases.Ageing research reviews · 2022Review
- Structural Plasticity of the Hippocampus in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The generation and maturation of adult neural stem/progenitor cells are impaired in many neurodegenerative diseases, among them is Parkinson's disease (PD). In mammals, including humans, adult neurogenesis is a lifelong feature of cellular brain plasticity in the hippocampal dentate gyrus (DG) and in the subventricular zone (SVZ)/olfactory bulb system. Hyposmia, depression, and anxiety are early non-motor symptoms in PD. There are parallels between brain regions associated with non-motor symptoms in PD and neurogenic regions. In autosomal dominant PD, mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequent. LRRK2 homologs in non-vertebrate systems play an important role in chemotaxis, cell polarity, and neurite arborization. We investigated adult neurogenesis and the neurite development of new neurons in the DG and SVZ/olfactory bulb system in bacterial artificial chromosome (BAC) human Lrrk2 G2019S transgenic mice. We report that mutant human Lrrk2 is highly expressed in the hippocampus in the DG and the SVZ of adult Lrrk2 G2019S mice. Proliferation of newly generated cells is significantly decreased and survival of newly generated neurons in the DG and olfactory bulb is also severely impaired. In addition, after stereotactic injection of a GFP retrovirus, newly generated neurons in the DG of Lrrk2 G2019S mice exhibited reduced dendritic arborization and fewer spines. This loss in mature, developed spines might point towards a decrease in synaptic connectivity. Interestingly, physical activity partially reverses the decrease in neuroblasts observed in Lrrk2 G2010S mice. These data further support a role for Lrrk2 in neuronal morphogenesis and provide new insights into the role of Lrrk2 in adult neurogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.