Direct and Retrograde Transduction of Nigral Neurons with AAV6, 8, and 9 and Intraneuronal Persistence of Viral Particles

Löw, Karin; Aebischer, Patrick; Schneider, Bernard L.

doi:10.1089/hum.2012.174

Cited by 51 publications

(40 citation statements)

References 51 publications

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“…Importantly, upon sectioning the brain no fluorescent signal was observed in the somatosensory cortex, a region projecting to the thalamus, supporting the idea that virus did not transport from the injection site to effect other brain nuclei resulting in our observed response but caution must be taken as the AAV5 and AAV6 serotype can result in axonal transport (Aschauer et al, 2013; Low et al, 2013; Salegio et al, 2013). …”

Section: Discussionsupporting

confidence: 77%

Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus

et al. 2017

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Pain is a common complication of herpes zoster (HZ) infection which results from reactivation of a latent varicella zoster virus (VZV). A third of HZ patients’ progress to a chronic pain state known as post herpetic neuralgia (PHN), and about a quarter of these patients’ have orofacial pain. The mechanisms controlling the pain responses are not understood. Studies suggest central pathways involving the thalamus could control pain related to HZ, and studies in our lab suggest vesicular GABA transporter (VGAT) in the lateral thalamus influences orofacial pain. We hypothesized that thalamic VGAT functions, in part, to reduce pain, particularly orofacial pain, associated with VZV. To address this hypothesis VZV was injected into the whisker pad. Affective and motivational aspects of pain were measured using the Place Escape/Avoidance Paradigm. Thalamic neuronal activity was modulated after injecting an adeno-associated virus (AAV) expressing an engineered acetylcholine Gi-protein coupled receptor. This receptor inhibits neuronal firing when bound by clozapine-n-oxide (CNO). VGAT expression was attenuated in the thalamus by injecting an AAV construct that expressed a VGAT silencing shRNA. VZV induced nociception was significantly decreased after administering CNO in male rats. Nociception significantly increased concomitant with increased thalamic c-fos expression after attenuating thalamic VGAT expression. These data establish that the lateral thalamus (posterior, ventral posteromedial, ventral posterolateral and/or reticular thalamic nucleus) controls VZV induced nociception in the orofacial region, and that GABA in this region appears to reduce the response to VZV induced nociception possibly by gating facial pain input.

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Section: Discussionsupporting

confidence: 77%

Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus

et al. 2017

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“…AAV vectors pseudotyped with the serotype‐6 capsid were prepared as previously described (Löw et al ., ). AAV2/6 particles were produced by transient transfection of the pDP6 and pAAV‐pgk‐β‐globin intron‐WPRE plasmids in 293‐AAV cells.…”

Section: Methodsmentioning

confidence: 97%

Motor deficits and beta oscillations are dissociable in an alpha‐synuclein model of Parkinson's disease

Brys

Nunes²,

Fuentes

2017

Eur J of Neuroscience

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Parkinson's disease (PD) is a neurodegenerative disorder characterised by progressive motor symptoms resulting from chronic loss of dopaminergic neurons in the nigrostriatal pathway. The over expression of the protein alpha-synuclein in the substantia nigra has been used to induce progressive dopaminergic neuronal loss and to reproduce key histopathological and temporal features of PD in animal models. However, the neurophysiological aspects of the alpha-synuclein PD model have been poorly characterised. Hereby, we performed chronic in vivo electrophysiological recordings in the corticostriatal circuit of rats injected with viral vector to over express alpha-synuclein in the right substantia nigra. Our model, previously shown to exhibit mild motor deficits, presented moderate dopaminergic cell loss but did not present prominent local field potential oscillations in the beta frequency range (11-30 Hz), considered a hallmark of PD, during the 9 weeks after onset of alpha-synuclein over expression. Spinal cord stimulation, a potential PD symptomatic therapy, was applied regularly from sixth to ninth week after alpha-synuclein over expression onset and had an inhibitory effect on the firing rate of corticostriatal neurons in both control and alpha-synuclein hemispheres. Dopamine synthesis inhibition at the end of the experiment resulted in severe parkinsonian symptoms such as akinesia and increased beta and high-frequency (>90 Hz) oscillations. These results suggest that the alpha-synuclein PD model with moderate level of dopaminergic depletion does not reproduce the prominent corticostriatal beta oscillatory activity associated to parkinsonian conditions.

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“…One solution to overcome this limitation can lie in the use of vectors capable of retrograde transport to distal neuronal projection sites. This can be achieved by using specific envelopes for lentiviral vectors derived from the Rhabdoviridae family or specific AAV serotypes [103,104,105,106].…”

Section: Gene Therapy Stem Cell Transplantation and Genome Editingmentioning

confidence: 99%

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

Didiášová¹,

Banning²,

Brennenstuhl³

et al. 2020

Preprint

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Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by the impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degree of mental retardation, autism, ataxia and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential use of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between the researchers and the patients.

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Direct and Retrograde Transduction of Nigral Neurons with AAV6, 8, and 9 and Intraneuronal Persistence of Viral Particles

Cited by 51 publications

References 51 publications

Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus

Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus

Motor deficits and beta oscillations are dissociable in an alpha‐synuclein model of Parkinson's disease

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

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