Optimizing animal models for HIV-associated CNS dysfunction and CNS reservoir research

Joseph, Jeymohan

doi:10.1007/s13365-018-0631-7

Cited by 6 publications

(6 citation statements)

References 12 publications

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“…The choice of animal models in studying HAND has been fraught with limitations since HIV‐1 does not infect rodents. While none of the models developed can recapitulate the human syndrome of HAND, several small animal models have been exploited to address specific questions and aspects of HAND pathogenesis [48,49]. Herein we chose to focus on the HIV‐1 Tg rats that constitutively express 7 of the 9 viral proteins throughout the lifespan.…”

Section: Discussionmentioning

confidence: 99%

Neuronal‐derived extracellular vesicles are enriched in the brain and serum of HIV‐1 transgenic rats

Dagur

Liao

Sil

et al. 2019

J of Extracellular Vesicle

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Despite the efficacy of combination antiretroviral therapy (ART) in controlling human immunodeficiency virus (HIV-1) replication, cytotoxic viral proteins such as HIV-1 transactivator of transcription (Tat) persist in tissues such as the brain. Although HIV-1 does not infect neuronal cells, it is susceptible to viral Tat protein-mediated toxicity, leading to neuroinflammation that underlies HIV-associated neurocognitive disorders (HAND). Given the role of extracellular vesicles (EVs) in both cellular homoeostasis and under pathological conditions, we sought to investigate the alterations in the quantity of neuronal-derived EVs in the brainas defined by the presence of cell adhesion molecule L1 (L1CAM) and to evaluate the presence of L1CAM + EVs in the peripheral circulation of HIV-1 transgenic (HIV-1 Tg) rats. The primary goal of this study was to investigate the effect of long-term exposure of HIV-1 viral proteins on the release of neuronal EVs in the brain and their transfer in the systemic compartment. Brain and serum EVs were isolated from both wild type and HIV-1 Tg rats using differential ultracentrifugation with further purification using the Optiprep gradient method. The subpopulation of neuronal EVs was further enriched using immunoprecipitation. The current findings demonstrated increased presence of L1CAM + neuronal-derived EVs both in the brain and serum of HIV-1 Tg rats.

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Section: Discussionmentioning

confidence: 99%

Neuronal‐derived extracellular vesicles are enriched in the brain and serum of HIV‐1 transgenic rats

Dagur

Liao

Sil

et al. 2019

J of Extracellular Vesicle

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“…Many other diseases can cause behavioural changes that are very similar to those caused by CDS. Hypertension, hyperthyroidism, feline immunodeficiency virus (FIV) infection, and recrudescent toxoplasmosis in particular can present with identical behavioural changes [6,9,[17][18][19][20]. While additional clinical signs would usually suggest that one of these other diseases was more likely, e.g., hyphaemia or retinal haemorrhage with hypertension, or weight loss with hyperthyroidism, these other signs are not always present, so a full investigation is always needed.…”

Section: Behavioural Changes Related To Cds (Vishdaal)mentioning

confidence: 99%

“…[9,21,22]. Cognitive decline due to FIV-associated neuroinflammation compares with HIV-associated neurocognitive dysfunction (HAND) in people, where the clinical signs can include abnormal stereotypic behaviours, aggression, changes in sleep architecture, and impaired cognitive and motor functions [17][18][19][20].…”

Section: Behavioural Changes Related To Cds (Vishdaal)mentioning

confidence: 99%

Potential Causes of Increased Vocalisation in Elderly Cats with Cognitive Dysfunction Syndrome as Assessed by Their Owners

Černá

Gardiner²,

Sordo

et al. 2020

Animals

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The objectives of this study were to explore owner perception of the causes of increased vocalisation in cats diagnosed with cognitive dysfunction syndrome (CDS) and consider what impact this vocalisation may have on the cat’s household. Owners of cats diagnosed with CDS that presented with increased vocalisation were invited to complete an online survey. The survey consisted of 28 questions including the cat’s signalment, its medical history, and questions pertaining to the owner’s perception of what motivated their cat´s increased vocalisation. This was determined by looking at the cat’s behaviour when vocalising, where it was looking when it was vocalising, and if the vocalisation stopped when the owner interacted with it, e.g., petting or feeding it. The owners were also asked how stressful they found their cat’s vocalisation. There were 37 responses. The majority of owners reported that the main cause of their cat’s vocalisation appeared to be disorientation (40.5%) or attention seeking (40.5%). Seeking a resource such as food was reported in 16.2%, and pain was perceived to be the cause in only 2.7% of cats. However, the majority of owners (64.8%) believed there was >1 cause of their cat’s increased vocalisation. Importantly, when owners were asked how stressful they found their cat’s increased vocalisation, 40.5% scored ≥3 (where 1 = not stressful; 5 = significantly stressful). This study provides novel insight into owner perception of feline CDS, as well as potential causes for increased vocalisation; this will allow veterinarians to better advise owners on how to manage their cat with CDS.

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“…[24][25][26][27] Infection with FIV shares similar clinical features with HIV infection. 28 The pathological effects of FIV infection on the central nervous system (CNS) of cats closely parallel the effects of HIV on the human CNS [29][30][31][32] and cognitive impairments have been documented in FIV-infected cats. [33][34][35][36] Many of the current reports on cognitive deficits caused by FIV were specifically addressed experimentally infected cats.…”

Section: Introductionmentioning

confidence: 99%

Age‐related cognitive impairments in domestic cats naturally infected with feline immunodeficiency virus

Azadian

Gunn-Moore

2022

Veterinary Record

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Background Age‐related dementia has been documented in domestic cats; however, its interaction with naturally occurring feline immunodeficiency virus (FIV) infection has been investigated minimally. Methods Visuospatial working memory (VSWM) and problem‐solving (PS) ability were evaluated in FIV‐infected (n = 37) and control cats (n = 39) using two cognitive tasks tested serially, which assessed the ability of cats to remember the location of a baited container after a set delay, then evaluated the capability of the cats to manipulate the container to obtain the food within a time limit. Cats were categorized using 7 years of age as a cut‐off to determine age‐related differences. The relationship between cognitive performance and FIV viral load was investigated using real‐time PCR cycle threshold (Ct) values. Results Age significantly affected VSWM and PS ability. Younger cats had better VSWM performance and PS ability compared to older cats with the same FIV status. There was no difference between younger FIV‐positive and negative cats in either part of the task. While older FIV‐positive cats had significantly worse VSWM than older FIV‐negative cats, no differences were found in PS ability. Additionally, Ct values predicted VSWM but not PS ability. Conclusion Age‐related cognitive impairments and FIV infection appear synergetic, causing greater cognitive deficits in older FIV‐infected cats.

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Optimizing animal models for HIV-associated CNS dysfunction and CNS reservoir research

Cited by 6 publications

References 12 publications

Neuronal‐derived extracellular vesicles are enriched in the brain and serum of HIV‐1 transgenic rats

Neuronal‐derived extracellular vesicles are enriched in the brain and serum of HIV‐1 transgenic rats

Potential Causes of Increased Vocalisation in Elderly Cats with Cognitive Dysfunction Syndrome as Assessed by Their Owners

Age‐related cognitive impairments in domestic cats naturally infected with feline immunodeficiency virus

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