A5022030316- Lysosomal Storage Disorders Research
- Neuroscience and Neuropharmacology Research
- Virus-based gene therapy research
- Neurogenesis and neuroplasticity mechanisms
- Alzheimer's disease research and treatments
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Nerve injury and regeneration
- Pluripotent Stem Cells Research
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- Glycogen Storage Diseases and Myoclonus
- Tryptophan and brain disorders
- Calcium signaling and nucleotide metabolism
- Memory and Neural Mechanisms
- Metabolism and Genetic Disorders
- S100 Proteins and Annexins
- Cannabis and Cannabinoid Research
- Neurological disorders and treatments
- Mesenchymal stem cell research
University of Otago
2015-2024
Brain Research New Zealand
2015-2024
University of Auckland
2006-2021
Beaumont Hospital
2017-2019
Research Network (United States)
2015
Northern Kentucky University
2008
Highland Community College - Illinois
2008
University of Iowa
2002-2003
University of Rochester Medical Center
2002
Victoria University of Wellington
1999-2001
Neutrophil accumulation is a well-established feature of Alzheimer's disease (AD) and has been linked to cognitive impairment by modulating disease-relevant neuroinflammatory vascular pathways. Neutrophils express high levels the oxidant-generating enzyme myeloperoxidase (MPO), however there controversy regarding cellular source localisation MPO in AD brain.We used immunostaining immunoassays quantify neutrophils human tissue microarrays brains APP/PS1 mice. We also multiplexed...
In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant structures drive movement. Despite their pivotal position and acknowledged diversity these are traditionally separated into broad commissural corticofugal types, until now no attempt has been made at resolving basis for diversity. We therefore probed electrophysiological morphological properties of retrogradely labeled M1 corticospinal (CSp), corticothalamic (CTh), projecting corticostriatal (CStr)...
Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance [MRI] computed tomography [CT] scanning), a far greater challenge associated with subsequent management mild TBI (mTBI), especially concussion which, by definition, characterized normal CT. To investigate whether integrity blood–brain barrier (BBB) altered in high-risk population for concussions, we studied professional mixed martial arts (MMA)...
Adeno-associated viral (AAV) vectors are attractive tools for central nervous system (CNS) gene therapy because some can cross the blood-brain barrier (BBB), allowing them to be used as minimally invasive treatments. A novel AAV vector recently evolved in vivo, AAV-PHP.eB, has been reported BBB more effectively than existing gold standard AAV9, but not under all conditions. Here, we compared efficacy of single-stranded AAV-PHP.eB and AAV9 targeting mouse CNS peripheral tissues after...
Gene transfer vectors based on lentiviruses can transduce terminally differentiated cells in the brain; however, their ability to reverse established behavioral deficits animal models of neurodegeneration has not previously been tested. When recombinant feline immunodeficiency virus (FIV)-based expressing β-glucuronidase were unilaterally injected into striatum adult deficient [mucopolysaccharidosis type VII (MPS VII)] mice, an model lysosomal storage disease, there was bihemispheric...
Our data demonstrate that vectors derived from recombinant feline immunodeficiency virus (rFIV) and adeno-associated type 5 (rAAV5) transduce cerebellar cells following direct injection into the lobules of mice. Both viruses mediated gene transfer predominantly to neurons, with up 2500 1500 Purkinje transduced for rAAV5 or rFIV-based vectors, respectively. The also stellate, basket Golgi occasional transduction granule deep nuclei. spread outside cerebellum inferior colliculus ventricular...
Abstract Brain‐derived neurotrophic factor (BDNF) plays a major role in regulating the survival and fate of progenitor cells adult brain. In order to extend previous observations normal brain advance our knowledge regarding effect BDNF on neurogenesis injured brain, this study directly compared basal injury‐induced relation cell distribution levels neuronal differentiation survival. was overexpressed subventricular zone (SVZ) via recombinant adeno‐associated virus (AAV 1/2 ) delivery, newly...
A hippocampal-diencephalic-cortical network supports memory function. The anterior thalamic nuclei (ATN) form a key anatomical hub within this system. Consistent with this, injury to the mammillary body-ATN axis is associated examples of clinical amnesia. However, there only limited and indirect support that output ATN neurons actively enhances memory. Here, in rats, we first showed mammillothalamic tract (MTT) lesions caused persistent impairment spatial working MTT also reduced rhythmic...
Alzheimer's disease (AD) is a neurodegenerative driven in large part by accumulated deposits the brain of amyloid precursor protein (APP) cleavage product amyloid-β peptide (Aβ). However, AD also characterised reductions secreted protein-alpha (sAPPα), an alternative APP. In contrast to neurotoxicity Αβ, sAPPα has many neuroprotective and neurotrophic properties. Increasing levels potential serve as therapeutic treatment that mitigates effects Aβ rescue cognitive function. Here we tested...
CLN6-Batten disease, a form of neuronal ceroid lipofuscinosis is rare lysosomal storage disorder presenting with gradual declines in motor, visual, and cognitive abilities early death by 12-15 years age. We developed self-complementary adeno-associated virus serotype 9 (scAAV9) vector expressing the human CLN6 gene under control chicken β-actin (CB) hybrid promoter. Intrathecal delivery scAAV9.CB.hCLN6 into cerebrospinal fluid (CSF) lumbar spinal cord 4-year-old non-human primates was safe,...
<h2>Abstract</h2> Neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. The expression of therapeutic proteins by neural progenitors would be enhanced viral-mediated transfer, but the effects several common recombinant viruses on primary populations have not been tested. To address this issue, we cultured from embryonic day 16–18 mouse brain serum-free medium containing epidermal growth factor basic fibroblast factor, and...
The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are inherited neurodegenerative lysosomal storage diseases with common clinical features of blindness and seizures culminating in premature death. Gene-therapy strategies for these depend on whether the missing activity is a secreted protein taken up by neighboring cells, or an intramembrane that requires careful targeting. Therapies best developed animal models large complex human-like brains. Lentiviral-mediated gene delivery to...
High-frequency deep brain stimulation (DBS) in motor thalamus (Mthal) ameliorates tremor but not akinesia Parkinson's disease. The aim of this study was to investigate whether there are effective methods Mthal treat akinesia. Glutamatergic neurons, transduced with channelrhodopsin-2 by injection lentiviral vector (Lenti.CaMKII.hChR2(H134R).mCherry), were selectively stimulated blue light (473 nm) via a chronically implanted fiber-optic probe. Rats performed reach-to-grasp task either acute...
Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, anti-seizure effects. Here, we determined the effects of chronic CBD administration in mouse model CLN1 disease (Cln1-/-) that simultaneously exhibits neuroinflammation, neurodegeneration, spontaneous seizures. Proteomic analysis showed putative receptors are expressed at similar levels brains Cln1-/- mice compared normal animals. received an oral dose (100 mg/kg/day) for...
The transcription factor encoded by Fez family zinc finger 2 ( Fezf2 ) is necessary for normal development of the cerebral cortex. However, continues to be expressed in mature brain, indicating that it might also cortical function throughout life. Here, we show a unique identity -expressing intratelencephalic-projection neurons (IT-PNs) layer 5 mouse motor cortex, using Fezf2–Gfp reporter mouse, vivo retrograde labeling, whole-cell electrophysiology with morphology reconstruction, and...