PMID- 33818687
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20220326
IS  - 2509-2723 (Electronic)
IS  - 2509-2715 (Print)
IS  - 2509-2723 (Linking)
VI  - 43
IP  - 4
DP  - 2021 Aug
TI  - In vivo proton magnetic resonance spectroscopy detection of metabolite 
      abnormalities in aged Tat-transgenic mouse brain.
PG  - 1851-1862
LID - 10.1007/s11357-021-00354-w [doi]
AB  - Most individuals living with HIV in the USA are over 45 years old and are 
      vulnerable to the combined effects of HIV and aging. Antiretroviral therapies 
      reduce HIV morbidity and mortality but do not prevent HIV trans-activator of 
      transcription (Tat) protein expression or development of HIV-associated 
      neurocognitive disorder (HAND), which may be caused by Tat. Tat-transgenic 
      (Tat-tg) mice are used to study Tat's effects, typically after transgene 
      induction with doxycycline. However, uninduced Tat-tg mice experience transgene 
      leak and model aspects of HAND when aged, including neuroinflammation. We used in 
      vivo 9.4-tesla proton magnetic resonance spectroscopy to compare neurochemistry 
      in aged versus young female and male uninduced Tat-tg mice. Aged Tat-tg mice 
      demonstrated measurable tat mRNA brain expression and had lower medial prefrontal 
      cortex (MPFC) GABA, glutamate, and taurine levels and lower striatal GABA and 
      taurine levels. Females had lower MPFC glutathione and taurine and lower striatal 
      taurine levels. Brain testosterone levels were negatively correlated with age in 
      aged males but not females. Aged mice had cortical abnormalities not previously 
      reported in aged wild-type mice including lower MPFC GABA and taurine levels. As 
      glutathione and taurine levels reflect inflammation and oxidative stress, our 
      data suggest that Tat may exacerbate these processes in aged Tat-tg mice. 
      However, additional studies in controls not expressing Tat are needed to confirm 
      this point and to deconvolve individual effects of age and Tat expression. Sex 
      steroid hormone supplements, which counter climacteric effects, increase taurine 
      levels, and reduce inflammation and oxidative stress, could attenuate some of the 
      brain abnormalities we identified in aged Tat-tg mice.
CI  - (c) 2021. American Aging Association.
FAU - Paris, Jason J
AU  - Paris JJ
AUID- ORCID: 0000-0002-5628-1134
AD  - Department of BioMolecular Sciences, School of Pharmacy, University of 
      Mississippi, University, MS, 38677, USA.
FAU - Chen, Xi
AU  - Chen X
AD  - McLean Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA, 
      02478, USA.
FAU - Anderson, Joseph
AU  - Anderson J
AD  - McLean Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA, 
      02478, USA.
FAU - Qrareya, Alaa N
AU  - Qrareya AN
AUID- ORCID: 0000-0001-5033-8382
AD  - Department of BioMolecular Sciences, School of Pharmacy, University of 
      Mississippi, University, MS, 38677, USA.
FAU - Mahdi, Fakhri
AU  - Mahdi F
AUID- ORCID: 0000-0003-4891-2992
AD  - Department of BioMolecular Sciences, School of Pharmacy, University of 
      Mississippi, University, MS, 38677, USA.
FAU - Du, Fei
AU  - Du F
AD  - McLean Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA, 
      02478, USA.
FAU - McLaughlin, Jay P
AU  - McLaughlin JP
AUID- ORCID: 0000-0001-9851-9342
AD  - Department of Pharmacodynamics, College of Pharmacy, University of Florida, 
      Gainesville, FL, 32610, USA.
FAU - Kaufman, Marc J
AU  - Kaufman MJ
AUID- ORCID: 0000-0002-4383-1264
AD  - McLean Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA, 
      02478, USA. kaufman@mclean.harvard.edu.
LA  - eng
GR  - R01 DA039044/DA/NIDA NIH HHS/United States
GR  - S10 RR019356/RR/NCRR NIH HHS/United States
GR  - P30 GM122733/GM/NIGMS NIH HHS/United States
GR  - R00 DA039791/DA/NIDA NIH HHS/United States
GR  - R01 DA052851/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210405
PL  - Switzerland
TA  - Geroscience
JT  - GeroScience
JID - 101686284
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Animals
MH  - *Brain/diagnostic imaging/metabolism
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Prefrontal Cortex/metabolism
MH  - Proton Magnetic Resonance Spectroscopy
MH  - *tat Gene Products, Human Immunodeficiency Virus/metabolism
PMC - PMC8492857
OTO - NOTNLM
OT  - Brain
OT  - Estradiol
OT  - Glutathione
OT  - HIV
OT  - Inflammation
OT  - Magnetic resonance spectroscopy
OT  - Oxidative stress
OT  - Sex difference
OT  - Tat
OT  - Taurine
OT  - Testosterone
COIS- The authors declare no competing interests.
EDAT- 2021/04/06 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/04/05
CRDT- 2021/04/05 12:42
PHST- 2020/12/14 00:00 [received]
PHST- 2021/03/10 00:00 [accepted]
PHST- 2021/04/06 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/04/05 12:42 [entrez]
PHST- 2021/04/05 00:00 [pmc-release]
AID - 10.1007/s11357-021-00354-w [pii]
AID - 354 [pii]
AID - 10.1007/s11357-021-00354-w [doi]
PST - ppublish
SO  - Geroscience. 2021 Aug;43(4):1851-1862. doi: 10.1007/s11357-021-00354-w. Epub 2021 
      Apr 5.