Corresponding author (BioMolecular Sciences): Alaa Qrareya, anqrarey@go.olemiss.eduhttps://egrove.olemiss.edu/pharm_annual_posters/1001/thumbnail.jp

Ashpole, Nicole M.

Mahdi, Fakhri

Paris, Jason J.

Qrareya, Alaa N.

English

eGrove (Univ. of Mississippi)

University of Mississippi eGrove Annual Poster Session 2020 Annual Poster Session 10-23-2020 R02. HIV-1 Tat Promotes Age-Related Anxiety-like, Antinociceptive, and Neuromuscular Impairments in Aged Male Mice Alaa N. Qrareya University of Mississippi, anqrarey@go.olemiss.edu Fakhri Mahdi University of Mississippi Nicole M. Ashpole University of Mississippi Jason J. Paris University of Mississippi Follow this and additional works at: https://egrove.olemiss.edu/pharm_annual_posters Recommended Citation Qrareya, Alaa N.; Mahdi, Fakhri; Ashpole, Nicole M.; and Paris, Jason J., "R02. HIV-1 Tat Promotes Age-Related Anxiety-like, Antinociceptive, and Neuromuscular Impairments in Aged Male Mice" (2020). Annual Poster Session 2020. 2. https://egrove.olemiss.edu/pharm_annual_posters/2 This Book is brought to you for free and open access by the Annual Poster Session at eGrove. It has been accepted for inclusion in Annual Poster Session 2020 by an authorized administrator of eGrove. For more information, please contact egrove@olemiss.edu. `HypothesesHIV-1 Tat expression will interact with aging as assessedby affective, antinociceptive, and neuromuscularcomorbidities. Tat may accelerate Age-relatedcomorbidities.MethodsSummaryHIV-1 Tat or Aging Influences Neuromuscular FunctionAging Potentiates Mechanical AllodyniaNeither Tat nor Aging Produce Thermal HyperalgesiaAcknowledgments:This work was supported by funds from NIDA (R00 DA039791; R01 DA052851), NIGMS (Adm. Suppl. to P30GM122733), and The University of MississippiHIV-1 Tat Promotes Age-Related Anxiety-like, Antinociceptive, and Neuromuscular Impairments in Aged Male MiceAlaa N. Qrareya1, Fakhri Mahdi1, Nicole M. Ashpole1,2, Jason J. Paris1,21Dept. of BioMolecular Sciences Dept., University of Mississippi 2Research Institute of Pharmaceutical Science, University of MississippiReferences HIV-1 Tat Expression and Aging Exacerbates Anxiety-like Behavior in an Elevated Plus MazeAA BBackgroundv Combination antiretroviral therapy (cART) has significantlyreduced the incidence of HIV-1 associated dementia and increasedlife expectancy among infected patients. However, ~50% of theHIV+ population still suffers from neurological and psychologicalsymptoms, including increased incidence of cognitive deficits,anxiety/depression, and neuropathic pain, collectively calledneuroHIV [1,3].v HIV-1 proteins, such as the trans-activator of transcription (Tat),are neurotoxic, remain present in the central nervous systemdespite combined antiretroviral therapy, and are thought tocontribute to neuroHIV [2, 4].v The U.S. HIV+ population is aging with over 60% of individuals45 years or older. These individuals experience accelerated agingand characterized by vulnerability to numerous age-relatedcomorbidities, including endocrine and immune dysfunction,neurocognitive deficits, vascular and metabolic disorders [4-6].v HIV-1 Tat protein, cART, and chronological aging can disruptendocrine function, dysregulate the hypothalamic-pituitary-adrenal and -gonadal axes, and impair steroidogenesis. [4-7].Animal HousingHIV-1 Tat transgenic mice were generated in the vivarium at the University ofMississippi (University, MS). HIV-1 Tat1-86 protein is expressed via a glial fibrillaryacidic protein (GFAP)-driven, tetracycline (Tet)-on promoter activated by doxycycline(30 mg/kg, i.p.). Middle-aged (6-8 mons) and Aged (11-13 mos), male (n=43) thatexpressed Tat (Tat+) and their non-Tat-expressing counterparts (Tat-) were housed (4-5/cage) in a temperature- and humidity-controlled room on a reversed 12:12 hlight/dark cycle (lights off at 20:00 h).Elevated Plus Maze (EPM)Mice were placed in the center of an elevated plus maxe (5× 5 cm) and allowed toexplore the maze for 5 min. Animals were tracked digitally using Noldus Ethovisiontracking software. The latency to enter, and time spent on, the open arms of the mazewere considered an index of anti-anxiety-like behavior.Grip StrengthThe apparatus consisted of a wire bar grid connected to a force transducer that recordedthe maximal force (g) created by gently pulling mice from the bar by the base of the tailuntil the grip was released. Grip strength was assessed independently for the forelimbsvs. all four limbs.Electronic Von Frey (eVF) Mechanical AllodyniaThe eVF probe was applied to the middle plantar surface of the hind paw and force wasincrementally increased until paw withdrawal. The required force (g) to produce thewithdrawal was recorded. Each mouse was tested in eight trials (4: right and 4: left)alternating between right and left paws with a 3-min interval break between trials.Thermal HyperalgesiaA radiant heat source was applied to the middle plantar surface of the hind paw(2.5 ̊C/sec) until paw withdrawal. Each mouse underwent 4 trials (2: right and 2: left)with a 3 -5 min interval break between trials.Figure 1: (A) Tat exposure and aging increased anxiety-like behavior. (D) Aged Tat + male showed a lower % open arm entries. * indicates Tat+significantly differs from respective Tat- control group. ^ indicates aged male significantly differs from respective middle-aged group. ‡ indicatessignificant difference from all other groups (2-way ANOVA, p < 0.05).Figure 2: (A) Irrespective of Tat exposure, aged mice demonstrated increased  mechanical allodynia. (B) Neither Tat nor aging influenced thermal hyperalgesia. † indicates Tat- control group significantly differs from all other groups  (2-way ANOVA , p < 0.05).BAAThus, HIV-1 Tat promoted anxiety–like behavior, allodynia, andneuromuscular dysfunction among aged mice. For neuromuscularfunction in particular, Tat expression accelerated age-related deficits.Future studies will determine whether administration of exogenoussteroid hormones can ameliorate Tat- and age-related comorbidities.BB1. Cañizares, Silvia, Mariana Cherner, and and Ronald J. Ellis. 2014. Seminars in Neurology 34 (1): 27–34. 2. Ensoli, Barbara, Valeria Fiorelli, Fabrizio Ensoli, Aurelio Cafaro, Fausto Titti, Stefano Buttò, Paolo Monini, Mauro Magnani, Antonella Caputo, and Enrico Garaci. 2006. Aids 20 (18): 2245–61. Aziz-Donnelly, Angela, and Taylor B. Harrison. 2017. Current Treatment Options in Neurology 19 (10). 3. Cherner, Mariana, Ronald J. Ellis, Deborah Lazzaretto, Corinna Young, Monica Rivera Mindt, J. Hampton Atkinson, Igor Grant, and Robert K. Heaton. 2004. Aids 18 (SUPPL. 1).4. Slama, Laurence, Lisa P. Jacobson, Xiuhong Li, Frank J. Palella Jr, Joseph B Margolick, Lawrence A. Kingsley, Dorothy J. Wiley, et al. 2016. The Journal of Acquired Immune Deficiency Syndromes. 5. Imai, Kentaro, Madeline Y. Sutton, Rennatus Mdodo, and Carlos del Rio. 2013. Obstetrics and Gynecology International 2013: 1–11. 6. Maingat, Ferdinand G., Maria J. Polyak, Amber M. Paul, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, and Christopher Power. 2013. FASEB Journal27 (2): 725–37.vHIV-1 Tat expression or aging increased anxiety-like behavior in theelevated plus maze (Fig. 1A-B)vAging increased mechanical allodynia with no effect on thermalhyperalgesia (Fig. 2A-B).vAging reduced neuromuscular function when assessed either byforepaws alone or all four limbs together (forepaws + hindpaws)(Fig.3A-B).vTat exposure and aging altered heart and spleen weight (Fig.4B-C).ConclusionHIV-1 Tat or Aging Alters Organ Weight (Proportional to Body Weight)Figure 3: Tat exposure or aging influenced muscle strength normalized to body weight (A) in forelimbs (B) in all four limbs exposure. † indicatesTat- control group significantly differs from all other groups . ^ indicates significant difference from aged Tat – group (2-way ANOVA, p < 0.05).Figure 4: (A) Neither Tat or aging altered brain weight.(B) Tat exposure and aging influenced heart weight .(C) Tat+ aged micehad a heavier spleen .(D) Neither Tat or aging altered liver weight. All body organs were normalized to body weight. ^ indicatesTat+ middle-aged male significantly differs from Tat- middle-aged and Tat+ Aged mice. § indicates significant difference fromall other groups. (2-way ANOVA, p < 0.05).Forepaws Only Forepaws and HindpawsC D§^ ^ †* * ‡ ††

R02. HIV-1 Tat Promotes Age-Related Anxiety-like, Antinociceptive, and Neuromuscular Impairments in Aged Male Mice

https://egrove.olemiss.edu/cgi/viewcontent.cgi?article=1001&context=pharm_annual_posters

R02. HIV-1 Tat Promotes Age-Related Anxiety-like, Antinociceptive, and Neuromuscular Impairments in Aged Male Mice

Abstract

Similar works

Full text

Available Versions

eGrove (Univ. of Mississippi)