Discipline of Physiology


Researcher: Ms Rivona Harricharan

Designation: Masters student

Study: The Role of the Pyroptotic Pathway in a Tat-induced Stressed Model of HIV-Associated Neurocognitive Disorder

Summary: Introduction: South Africa has a staggering prevalence of 6.4 million people infected with HIV, dominating the statistics with the highest incidence in the world. HIV-associated neurocognitive disorder (HAND) has emerged as a major conundrum, challenging scientists to devise new strategies to combat its destructive effects. Recent HIV research findings have revealed that pyroptosis (a programmed cell death mechanism which is pro-inflammatory in nature), occurs in HIV-infected lymphoid tissue.

Aim: This study aims to provide insight into whether pyroptosis could be a contributing factor leading to cell death and the development of HIV-related neuropathology.

Methods: Using stereotaxic techniques, Tat protein Clade B (10 µg/10 µl) was injected bilaterally into the hippocampus of male Wistar rats. The animals were subjected to restraint stress daily. Following decapitation, the dorsal and ventral hippocampi were harvested. Biochemical analysis was conducted using the Caspase-1 colorimetric and Interleukin-18 Enzyme-linked Immunosorbent (ELISA) assays. A p-value of 0.05 was considered significant.

Results: Caspase-1 activity in the dorsal hippocampi was not significant while significance was observed in the ventral hippocampi of the Tat + Stress group. Significant levels of IL-18 were observed in the dorsal and ventral aspects of the hippocampus.

Conclusion: Pyroptosis did not occur in the dorsal aspect of the hippocampus, prompting us to believe that apoptosis or autophagy predominate there. In the ventral hippocampus of the Tat + Stress group, significant caspase-1 activity corroborated with increased IL-18 levels, indicative of pyroptosis. These novel findings may encourage future researchers to consider alternate cell death mechanisms as possible causative agents of HIV-related neuropathogenesis.

Researcher: Ms Rivona Harricharan

Designation: Masters student

Study: Tat-induced histopathological alterations mediate hippocampus-associated behavioural impairments in rats

Summary: HIV-1 is a global catastrophe, and is exceedingly prevalent in Sub-Saharan Africa. HIV-associated neurocognitive disorder is characterized by symptoms such as motor impairments, a decline in cognition, and behavioural irregularities. The aim of this study was to provide insight into the fundamental behavioural and histopathological mechanisms underlying the development and progression of HIV-1 neuropathology.

Using stereotaxic techniques, Tat protein Clade B (1 µg/µl, 10 µl) was injected bilaterally into the dorsal hippocampus of male Sprague-Dawley rats. The Morris water maze (MWM) and novel object recognition test (NORT) were used to assess spatial learning and recognition memory, respectively. Haematoxylin and eosin staining was used to identify the histopathological changes.

A highly significant increase in latency to reach the hidden platform in the MWM implied that noteworthy hippocampal damage had occurred. Severe behavioural deficits were also observed in the NORT where the Tat-injected group showed a greater preference for a familiar object over a novel one. This damage was confirmed by the histopathological changes (increased astrogliosis, cells becoming eosinophilic and a significant reduction in the pyramidal cell layer) observed in the hippocampus. Additionally, increases in the hippocampal mass and protein were observed, consistent with the structural alterations.

This study highlights the relationship between hippocampal-associated behavioural changes and histologic alterations following stereotaxic intra-hippocampal administration of Tat protein in rats. The implications of this study may positively impact the fields of immunology and neuroscience by encouraging future researchers to consider novel strategies to understand the complexities of the pathogenesis of HIV-associated neurocognitive disorder.