↓ Skip to main content

Loss of cerebellar neurons in the progression of lentiviral disease: effects of CNS-permeant antiretroviral therapy

Overview of attention for article published in Journal of Neuroinflammation, October 2016
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
8 Dimensions

Readers on

mendeley
39 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Loss of cerebellar neurons in the progression of lentiviral disease: effects of CNS-permeant antiretroviral therapy
Published in
Journal of Neuroinflammation, October 2016
DOI 10.1186/s12974-016-0726-0
Pubmed ID
Authors

Christian Wächter, Lee E. Eiden, Nedye Naumann, Candan Depboylu, Eberhard Weihe

Abstract

The majority of investigations on HIV-associated neurocognitive disorders (HAND) neglect the cerebellum in spite of emerging evidence for its role in higher cognitive functions and dysfunctions in common neurodegenerative diseases. We systematically investigated the molecular and cellular responses of the cerebellum as contributors to lentiviral infection-induced neurodegeneration, in the simian immunodeficiency virus (SIV)-infected rhesus macaque model for HIV infection and HAND. Four cohorts of animals were studied: non-infected controls, SIV-infected asymptomatic animals, and SIV-infected AIDS-diseased animals with and without brain-permeant antiretroviral treatment. The antiretroviral utilized was 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG), a CNS-permeable nucleoside reverse transcriptase inhibitor. Quantitation of granule cells and Purkinje cells, of an established biomarker of SIV infection (gp41), of microglial/monocyte/macrophage markers (IBA-1, CD68, CD163), and of the astroglial marker (GFAP) were used to reveal cell-specific cerebellar responses to lentiviral infection and antiretroviral therapy (ART). The macromolecular integrity of the blood brain barrier was tested by albumin immunohistochemistry. Productive CNS infection was observed in the symptomatic stage of disease, and correlated with extensive microglial/macrophage and astrocyte activation, and widespread macromolecular blood brain barrier defects. Signs of productive infection, and inflammation, were reversed upon treatment with 6-Cl-ddG, except for a residual low-grade activation of microglial cells and astrocytes. There was an extensive loss of granule cells in the SIV-infected asymptomatic cohort, which was further increased in the symptomatic stage of the disease and persisted after 6-Cl-ddG (administered after the onset of symptoms of AIDS). In the symptomatic stage, Purkinje cell density was reduced. Purkinje cell loss was likewise unaffected by 6-Cl-ddG treatment at this time. Our findings suggest that neurodegenerative mechanisms are triggered by SIV infection early in the disease process, i. e., preceding large-scale cerebellar productive infection and marked neuroinflammation. These affect primarily granule cells early in disease, with later involvement of Purkinje cells, indicating differential vulnerability of the two neuronal populations. The results presented here indicate a role for the cerebellum in neuro-AIDS. They also support the conclusion that, in order to attenuate the development of motor and cognitive dysfunctions in HIV-positive individuals, CNS-permeant antiretroviral therapy combined with anti-inflammatory and neuroprotective treatment is indicated even before overt signs of CNS inflammation occur.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 10 26%
Student > Ph. D. Student 6 15%
Student > Bachelor 5 13%
Researcher 4 10%
Other 3 8%
Other 6 15%
Unknown 5 13%
Readers by discipline Count As %
Medicine and Dentistry 10 26%
Neuroscience 5 13%
Pharmacology, Toxicology and Pharmaceutical Science 5 13%
Agricultural and Biological Sciences 4 10%
Psychology 3 8%
Other 6 15%
Unknown 6 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 October 2017.
All research outputs
#10,525,343
of 11,877,834 outputs
Outputs from Journal of Neuroinflammation
#1,153
of 1,357 outputs
Outputs of similar age
#230,174
of 272,984 outputs
Outputs of similar age from Journal of Neuroinflammation
#11
of 15 outputs
Altmetric has tracked 11,877,834 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,357 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 272,984 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.