title: Tat-induced histopathological alterations mediate hippocampus-associated behavioural impairments in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Laboratory Medicine and Medical Sciences, Discipline of Human Physiology, University of KwaZulu-Natal, Westville Campus, Private Bag X 54001, Durban, 4000, South Africa. rivonah3@gmail.com.
authors.forename: Rivona
authors.initials: R
authors.lastname: Harricharan
authors.affiliation: School of Laboratory Medicine and Medical Sciences, Discipline of Human Physiology, University of KwaZulu-Natal, Westville Campus, Private Bag X 54001, Durban, 4000, South Africa. thaver@ukzn.ac.za.
authors.forename: Veneesha
authors.initials: V
authors.lastname: Thaver
authors.affiliation: School of Laboratory Medicine and Medical Sciences, Discipline of Human Physiology, University of KwaZulu-Natal, Westville Campus, Private Bag X 54001, Durban, 4000, South Africa. russell@ukzn.ac.za.
authors.forename: Vivienne A
authors.initials: VA
authors.lastname: Russell
authors.affiliation: School of Laboratory Medicine and Medical Sciences, Discipline of Human Physiology, University of KwaZulu-Natal, Westville Campus, Private Bag X 54001, Durban, 4000, South Africa. danielsw@ukzn.ac.za.
authors.forename: William M U
authors.initials: WM
authors.lastname: Daniels
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects*; D015497:HIV-1; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007267:Injections; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000523:psychology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry; D017966:Pyramidal Cells / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects; D013238:Stereotaxic Techniques; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000633:toxicity*
chemical_list: D009419:Nerve Tissue Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus