Talks

Academic Level (Author 1)

Faculty

Discipline/Specialty (Author 1)

Neuroscience

Academic Level (Author 2)

Staff

Discipline/Specialty (Author 2)

Neuroscience

Academic Level (Author 3)

Staff

Academic Level (Author 4)

Medical Student

Discipline/Specialty (Author 4)

Neuroscience

Academic Level (Author 5)

Medical Student

Discipline/Specialty (Author 5)

Neuroscience

Academic Level (Author 6)

Medical Student

Discipline/Specialty (Author 6)

Neuroscience

Academic Level (Author 7)

Medical Student

Discipline/Specialty (Author 7)

Neuroscience

Academic Level (Author 8)

Medical Student

Discipline/Specialty (Author 8)

Neuroscience

Academic Level (Author 9)

Medical Student

Discipline/Specialty (Author 9)

Neuroscience

Academic Level (Author 10)

Medical Student

Discipline/Specialty (Author 10)

Neuroscience

Discipline Track

Community/Public Health

Abstract

In 2021, an estimated 38.4 million people were living with Human immunodeficiency virus-1 (HIV). While the introduction of antiretroviral therapies (ART) has dramatically improved the length of survival of individuals, peripheral neuropathy still affects as many as 50% of HIV-infected individuals. The most frequently reported clinical manifestation of HIV-associated peripheral neuropathy is distal sensory polyneuropathy (HIV-DSP), and it is one of the most common neurologic complications of HIV in the combination antiretroviral therapies (cART) era. Despite these gaps in knowledge, no small animal model mimics peripheral neuropathy in PLWH, and the ART era is available. The main goal here is to determine if the HIV transgenic (HIV-tg) rats develop peripheral neuropathy with behavioral and pathological changes that mimic peripheral neuropathy in PLWH. Skin biopsies from the plantar area of the hind paw from behaviorally tested HIV-tg and WT rats were analyzed for intra-epidermal nerve fiber (IENF) density using immunostaining for the neuronal marker protein gene product 9.5 (PGP 9.5). We used vonfrey to test for mechanically allodynia and acetone test was used to test for thermal hypersensitivity. We also tested HIV-tg rats for spontaneous pain using the rat grimace scale (RGS) model. Finally, HIV-tg and WT were tested for neuroinflammation using Rat XL cytokine Array kit. HIV-tg rats show decreased IENF density, mechanical allodynia, hypersensitivity, and ongoing pain compared to WT. Our proteomic analysis data shows a strong inflammatory response in the brain of the HIV-tg rats compared to WT. These results demonstrate that HIV-tg rats develop peripheral neuropathy conditions with behavioral and pathological changes that mimic people living with HIV. Histopathological and proteomic tools, combined with testing sensory and ongoing aspects of pain, demonstrate that HIV-tg rats can serve as a translational model for HIV-related peripheral neuropathy, which will set the stage for future mechanistic and therapeutic studies that are still lacking.

This work is supported by NIH grants (DA053824 and DA051226).

Presentation Type

Talk

Download

Share

COinS
 

Characterization of Peripheral Neuropathy In HIV-1 Transgenic Rats

In 2021, an estimated 38.4 million people were living with Human immunodeficiency virus-1 (HIV). While the introduction of antiretroviral therapies (ART) has dramatically improved the length of survival of individuals, peripheral neuropathy still affects as many as 50% of HIV-infected individuals. The most frequently reported clinical manifestation of HIV-associated peripheral neuropathy is distal sensory polyneuropathy (HIV-DSP), and it is one of the most common neurologic complications of HIV in the combination antiretroviral therapies (cART) era. Despite these gaps in knowledge, no small animal model mimics peripheral neuropathy in PLWH, and the ART era is available. The main goal here is to determine if the HIV transgenic (HIV-tg) rats develop peripheral neuropathy with behavioral and pathological changes that mimic peripheral neuropathy in PLWH. Skin biopsies from the plantar area of the hind paw from behaviorally tested HIV-tg and WT rats were analyzed for intra-epidermal nerve fiber (IENF) density using immunostaining for the neuronal marker protein gene product 9.5 (PGP 9.5). We used vonfrey to test for mechanically allodynia and acetone test was used to test for thermal hypersensitivity. We also tested HIV-tg rats for spontaneous pain using the rat grimace scale (RGS) model. Finally, HIV-tg and WT were tested for neuroinflammation using Rat XL cytokine Array kit. HIV-tg rats show decreased IENF density, mechanical allodynia, hypersensitivity, and ongoing pain compared to WT. Our proteomic analysis data shows a strong inflammatory response in the brain of the HIV-tg rats compared to WT. These results demonstrate that HIV-tg rats develop peripheral neuropathy conditions with behavioral and pathological changes that mimic people living with HIV. Histopathological and proteomic tools, combined with testing sensory and ongoing aspects of pain, demonstrate that HIV-tg rats can serve as a translational model for HIV-related peripheral neuropathy, which will set the stage for future mechanistic and therapeutic studies that are still lacking.

This work is supported by NIH grants (DA053824 and DA051226).

 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.