PMID- 38514527
OWN - NLM
STAT- Publisher
LR  - 20240322
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
DP  - 2024 Mar 22
TI  - Acute Administration of HIV-1 Tat Protein Drives Glutamatergic Alterations in a 
      Rodent Model of HIV-Associated Neurocognitive Disorders.
LID - 10.1007/s12035-024-04113-8 [doi]
AB  - HIV-1-associated neurocognitive disorders (HAND) are a major comorbidity of HIV-1 
      infection, marked by impairment of executive function varying in severity. HAND 
      affects nearly half of people living with HIV (PLWH), with mild forms 
      predominating since the use of anti-retroviral therapies (ART). The HIV-1 
      transactivator of transcription (Tat) protein is found in the cerebrospinal fluid 
      of patients adherent to ART, and its administration or expression in animals 
      causes cognitive symptoms. Studies of Tat interaction with the 
      N-methyl-D-aspartate receptor (NMDAR) suggest that glutamate toxicity contributes 
      to Tat-induced impairments. To identify changes in regional glutamatergic 
      circuitry underlying cognitive impairment, we injected recombinant Tat86 or 
      saline to medial prefrontal cortex (mPFC) of male Sprague-Dawley rats. Rats were 
      assessed with behavioral tasks that involve intact functioning of mPFC including 
      the novel object recognition (NOR), spatial object recognition (SOR), and 
      temporal order (TO) tasks at 1 and 2 postoperative weeks. Following testing, mPFC 
      tissue was collected and analyzed by RT-PCR. Results showed Tat86 in mPFC-induced 
      impairment in SOR, and upregulation of Grin1 and Grin2a transcripts. To further 
      understand the mechanism of Tat toxicity, we assessed the effects of full-length 
      Tat101 on gene expression in mPFC by RNA sequencing. The results of RNAseq 
      suggest that glutamatergic effects of Tat86 are maintained with Tat101, as Grin2a 
      was upregulated in Tat101-injected tissue, among other differentially expressed 
      genes. Spatial learning and memory impairment and Grin2a upregulation suggest 
      that exposure to Tat protein drives adaptation in mPFC, altering the function of 
      circuitry supporting spatial learning and memory.
CI  - (c) 2024. The Author(s).
FAU - Duffy, Brenna C
AU  - Duffy BC
AUID- ORCID: 0000-0002-9355-1893
AD  - Department of Microbiology and Immunology, Drexel University College of Medicine, 
      Philadelphia, PA, USA.
AD  - Center for Molecular Virology and Translational Neuroscience, Institute for 
      Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 
      Philadelphia, PA, USA.
FAU - King, Kirsten M
AU  - King KM
AD  - Department of Microbiology and Immunology, Drexel University College of Medicine, 
      Philadelphia, PA, USA.
FAU - Nepal, Binod
AU  - Nepal B
AD  - Department of Microbiology and Immunology, Drexel University College of Medicine, 
      Philadelphia, PA, USA.
FAU - Nonnemacher, Michael R
AU  - Nonnemacher MR
AUID- ORCID: 0000-0003-4299-3779
AD  - Department of Microbiology and Immunology, Drexel University College of Medicine, 
      Philadelphia, PA, USA. mrn25@drexel.edu.
AD  - Center for Molecular Virology and Translational Neuroscience, Institute for 
      Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 
      Philadelphia, PA, USA. mrn25@drexel.edu.
AD  - Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. 
      mrn25@drexel.edu.
FAU - Kortagere, Sandhya
AU  - Kortagere S
AUID- ORCID: 0000-0002-3532-8669
AD  - Department of Microbiology and Immunology, Drexel University College of Medicine, 
      Philadelphia, PA, USA. sk673@drexel.edu.
AD  - Center for Molecular Virology and Translational Neuroscience, Institute for 
      Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 
      Philadelphia, PA, USA. sk673@drexel.edu.
LA  - eng
GR  - NIH-R01NS089435/NH/NIH HHS/United States
GR  - NIH-R01NS089435/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20240322
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
SB  - IM
OTO - NOTNLM
OT  - Glutamate
OT  - HAND
OT  - HIV-1
OT  - NMDAR
OT  - Novel object recognition
OT  - Transactivator of transcription
OT  - Working memory
OT  - mPFC
EDAT- 2024/03/22 06:44
MHDA- 2024/03/22 06:44
CRDT- 2024/03/22 00:15
PHST- 2024/01/20 00:00 [received]
PHST- 2024/03/12 00:00 [accepted]
PHST- 2024/03/22 06:44 [medline]
PHST- 2024/03/22 06:44 [pubmed]
PHST- 2024/03/22 00:15 [entrez]
AID - 10.1007/s12035-024-04113-8 [pii]
AID - 10.1007/s12035-024-04113-8 [doi]
PST - aheadofprint
SO  - Mol Neurobiol. 2024 Mar 22. doi: 10.1007/s12035-024-04113-8.