Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice

Schier, Christina J.; Marks, William D.; Paris, Jason J.; Barbour, Aaron J.; McLane, Virginia D.; Maragos, William F.; McQuiston, A. Rory; Knapp, Pamela E.; Hauser, Kurt F.

doi:10.1523/jneurosci.0622-17.2017

Cited by 51 publications

(47 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3), which suggests with the higher level of balance and coordination performance female mice are vulnerable to HIV-1 Tatinduced damage. Similar differences have been noted in HIV transgenic rat and Tat transgenic mice [67,81], which may be due to selective neuronal vulnerability to HIV Tat [82].…”

Section: Discussionsupporting

confidence: 67%

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Zhao

Fan²,

Vann³

et al. 2020

Aging and disease

View full text Add to dashboard Cite

HIV infects the central nervous system and causes HIV/neuroAIDS, which is predominantly manifested in the form of mild cognitive and motor disorder in the era of combination antiretroviral therapy. HIV Tat protein is known to be a major pathogenic factor for HIV/neuroAIDS through a myriad of direct and indirect mechanisms. However, most, if not all of studies involve short-time exposure of recombinant Tat protein in vitro or short-term Tat expression in vivo. In this study, we took advantage of the doxycycline-inducible brainspecific HIV-1 Tat transgenic mouse model, fed the animals for 12 months, and assessed behavioral, pathological, and epigenetic changes in these mice. Long-term Tat expression led to poorer short-and long-term memory, lower locomotor activity and impaired coordination and balance ability, increased astrocyte activation and compromised neuronal integrity, and decreased global genomic DNA methylation. There were sex-and brain region-dependent differences in behaviors, pathologies, and epigenetic changes resulting from long-term Tat expression. All these changes are reminiscent of accelerated aging, raising the possibility that HIV Tat contributes, at least in part, to HIV infection-associated accelerated aging in HIV-infected individuals. These findings also suggest another utility of this model for HIV infection-associated accelerated aging studies.

show abstract

Section: Discussionsupporting

confidence: 67%

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Zhao

Fan²,

Vann³

et al. 2020

Aging and disease

View full text Add to dashboard Cite

show abstract

“…Spine detection was manually corrected if necessary. Classification of spines into stubby, mushroom-like and filopodia was performed using the Imaris XTension classify spines with following definitions: stubby: spine length <0.75 μm; mushroom: spine length <3.5 μm, spine head width >0.35 μm and spine head width >spine neck width; filopodia: when it did not fit the criteria mentioned above ( Schier et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Pathway-specific dysregulation of striatal excitatory synapses by LRRK2 mutations

Chen

Soto

Dumrongprechachan

et al. 2020

eLife

View full text Add to dashboard Cite

LRRK2 is a kinase expressed in striatal spiny projection neurons (SPNs), cells which lose dopaminergic input in Parkinson’s disease (PD). R1441C and G2019S are the most common pathogenic mutations of LRRK2. How these mutations alter the structure and function of individual synapses on direct and indirect pathway SPNs is unknown and may reveal pre-clinical changes in dopamine-recipient neurons that predispose towards disease. Here, R1441C and G2019S knock-in mice enabled thorough evaluation of dendritic spines and synapses on pathway-identified SPNs. Biochemical synaptic preparations and super-resolution imaging revealed increased levels and altered organization of glutamatergic AMPA receptors in LRRK2 mutants. Relatedly, decreased frequency of miniature excitatory post-synaptic currents accompanied changes in dendritic spine nano-architecture, and single-synapse currents, evaluated using 2-photon glutamate uncaging. Overall, LRRK2 mutations reshaped synaptic structure and function, an effect exaggerated in R1441C dSPNs. These data open the possibility of new neuroprotective therapies aimed at SPN synapse function, prior to disease onset.

show abstract

“…Spine detection was manually corrected if necessary. Classification of spines into stubby, mushroom-like and filopodia was performed using the Imaris XTension classify spines with following definitions: stubby: spine length < 0.75 μm; mushroom: spine length < 3.5μm, spine head width >0.35 μm and spine head width > spine neck width; filopodia: when it did not fit the criteria mentioned above 55 .…”

Section: Confocal Microscopy and Dendritic Spine Analysismentioning

confidence: 99%

Pathway-specific deregulation of striatal excitatory synapses in LRRK2 mutations

Chen

Soto

Bannon

et al. 2020

Preprint

View full text Add to dashboard Cite

ABSTRACTLRRK2 is a kinase expressed in striatal spiny projection neurons (SPNs), cells which lose dopaminergic input in Parkinson’s disease (PD). R1441C and G2019S are the most common pathogenic mutations of LRRK2. How these mutations alter the structure and function of individual synapses on direct and indirect pathway SPNs is unknown and may reveal pre-clinical changes in dopamine-recipient neurons that predispose towards disease. Here, R1441C and G2019S knock-in mice enabled thorough evaluation of dendritic spines and synapses on pathway-identified SPNs. Biochemical synaptic preparations and super-resolution imaging revealed increased levels and altered organization of glutamatergic AMPA receptors in LRRK2 mutants. Relatedly, decreased frequency of excitatory post-synaptic currents accompanied changes in dendritic spine nano-architecture, and single-synapse currents, evaluated using 2-photon glutamate uncaging. Overall, LRRK2 mutations reshaped synaptic structure and function, an effect exaggerated in R1441C dSPNs. These data open the possibility of new neuroprotective therapies aimed at SPN synapse function, prior to disease onset.

show abstract

Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice

Cited by 51 publications

References 99 publications

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Pathway-specific dysregulation of striatal excitatory synapses by LRRK2 mutations

Pathway-specific deregulation of striatal excitatory synapses in LRRK2 mutations

Contact Info

Product

Resources

About