Lentiviral Transduction of Neurons in Adult Brain: Evaluation of Inflammatory Response and Cognitive Effects in Mice

Kunitsyna, Tatiana A.; Ivashkina, Olga I.; Roshchina, M. A.; Торопова, К. А.; Анохин, К. В.

doi:10.1007/s10517-016-3404-4

Cited by 6 publications

(3 citation statements)

References 12 publications

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“…We avoided using this approach because microglia can respond to viral infection (Kunitsyna et al, 2016;Martianova et al, 2019), which may be a confounder in these types of studies. In virusinfected animals, CNO-induced activation of hM3Dq was able to elicit allodynia in male rats (Grace et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice

Binning

Hogan-Cann

Sakae

et al. 2020

Brain, Behavior, and Immunity

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Section: Discussionmentioning

confidence: 99%

Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice

Binning

Hogan-Cann

Sakae

et al. 2020

Brain, Behavior, and Immunity

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“…In this study we found that expression of Il1b and Ccl2 are increased in the VTA of mice expressing shMdk, and that Ccl2 expression is increased in the VTA of Mdk −/− mice. One caveat to the lentiviral injections is that the lentivirus could potentially activate glia at the site of injection, causing increased cytokine expression (Kunitsyna et al 2016). Since we found that Ccl2 expression increased in both the Mdk knockout mice and in mice injected with Mdk lentivirus, it is likely that this increase is due to a specific effect of decreased Mdk levels.…”

Section: Discussionmentioning

confidence: 99%

Midkine in the mouse ventral tegmental area limits ethanol intake and Ccl2 gene expression

Lasek

2017

Genes Brain and Behavior

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Midkine (MDK) is a cytokine and neurotrophic factor that is more highly expressed in the brains of human alcoholics and in mice predisposed to drink large amounts of ethanol, suggesting that MDK may regulate ethanol consumption. Here we measured ethanol consumption in male and female Mdk knockout (−/−) mice using the two-bottle choice and the drinking in the dark (DID) tests. We found that Mdk −/− mice consumed significantly more ethanol than wild type controls in both tests. To determine if MDK acts in the ventral tegmental area (VTA) to regulate ethanol consumption, we delivered lentivirus expressing a Mdk shRNA into the VTA of male C57BL/6J mice to locally knockdown Mdk and performed the DID test. Mice expressing a Mdk shRNA in the VTA consumed more ethanol than mice expressing a control non-targeting shRNA, demonstrating that the VTA is one site in the brain through which MDK acts to regulate ethanol consumption. Since MDK also controls the expression of inflammatory cytokines in other organs, we examined gene expression of interleukin-1 beta (Il1b), tumor necrosis factor alpha (Tnf) and the chemokine (C-C motif) ligand 2 (Ccl2) in the VTA of Mdk −/− mice and in mice expressing Mdk shRNA in the VTA. Expression of Ccl2 was elevated in the VTA of Mdk −/− mice and in mice expressing Mdk shRNA in the VTA. These results demonstrate that MDK functions in the VTA to limit ethanol consumption and levels of CCL2, a chemokine known to increase ethanol consumption.

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“…However, it has been shown that intra-hippocampal injection of a lentiviral particles (p156-CMV-EGFP, which is a similar construct to ours) with minimum content of transgenes does not change learning and memory of mice in the hippocampal-dependent fear conditioning task (Kunitsyna et al, 2016). Therefore, it is unlikely that GFP expression per se could improve avoidance memory in our study.…”

Section: Discussionmentioning

confidence: 55%

Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif

et al. 2021

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Rabies is a life-threatening viral infection of the brain. Rabies virus (RABV) merely infects excitable cells including neurons provoking drastic behaviors including negative emotional memories. RABV glycoprotein (RVG) plays a critical role in RABV pathogenesis. RVG interacts with various cytoplasmic PDZ (PSD-95/Dlg/ZO-1) containing proteins through its PDZ binding motif (PBM). PTZ domains have crucial role in formation and function of signal transduction.Hippocampus is one of the cerebral regions that contains high load of viral antigens. We examined impact of RVG expression in the dorsal hippocampus on aversive as well as spatial learning and memory performance in rats.Two μl of the lentiviral vector (~10 8 T.U. /ml) encoding RVG or ∆RVG (deleted PBM) genomes was microinjected into the hippocampal CA1. After one week, rat's brain was cross-sectioned and RVG/∆RVG-expressing neuronal cells were confirmed by fluorescent microscopy. Passive avoidance and spatial learning and memory were assessed in rats by Shuttle box and Morris water maze (MWM).In the shuttle box, both RVG and ∆RVG decreased the time spent in the dark compartment compared to control (p<0.05). In MWM, RVG and ∆RVG did not affect the acquisition of spatial task. RVG-expressing rats reached the platform position in the probe test sooner than control and ∆RVG groups (p<0.05). Rats expressing ∆RVG significantly swam farther from the hidden platform than RVG group (p<0.05).Our data indicate RVG expression in the hippocampus strengthens aversive and spatial learning and memory performance. The boosting effect on spatial but not avoidance memory is mediated through PBM.

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Lentiviral Transduction of Neurons in Adult Brain: Evaluation of Inflammatory Response and Cognitive Effects in Mice

Cited by 6 publications

References 12 publications

Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice

Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice

Midkine in the mouse ventral tegmental area limits ethanol intake and Ccl2 gene expression

Rabies virus glycoprotein enhances spatial memory via the PDZ binding motif

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