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bioRxiv · 10.64898/2026.04.06.716768

IMPAIRED BRIDGING OF TEMPORAL DISCONTINUITIES IN OLDER ADULT HIV-1 TG RATS

McLauriin, K. A.·Li, H.·Ritchie, A.·Booze, R. M.·Mactutus, C. F.
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Abstract

The advent and widespread uptake of combination antiretroviral therapy dramatically changed the epidemiological features of human immunodeficiency virus type 1 (HIV-1), whereby older individuals (>50 years of age) account for approximately 50% of HIV-1 seropositive individuals in the United States. Nevertheless, to date, there is no extant in vivo biological system to model the unique age-related neurocognitive impairments observed in HIV-1 seropositive individuals. Herein, the utility of the HIV-1 transgenic (Tg) rat as a biological system to model age-related neurocognitive impairments and neuroanatomical alterations was evaluated. Older adult HIV-1 Tg rodents (i.e., >12 months of age upon testing initiation), relative to their control counterparts, exhibited profound neurocognitive alterations characterized by impairments in stimulus-reinforcement learning, sustained attention, and selective attention; neurocognitive deficits which support a fundamental distortion of temporal processing. Neuronal dysfunction in older adult HIV-1 Tg animals was characterized by structural alterations in pyramidal neurons, and their associated dendritic spines, in the medial prefrontal cortex and abnormal accumulation of amyloid beta (A{beta}). Interestingly, the abnormal accumulation of A{beta} mechanistically underlies, at least in part, the profound dendritic spine dysmorphology in male, but not female, HIV-1 Tg rats. More critically, however, neuronal dysfunction mechanistically underlies neurocognitive impairments in both male and female HIV-1 Tg rodents, whereby neuronal dysfunction accounts for 65.4% and 60.8% of the variance in neurocognitive function, respectively. Establishing the utility of the HIV-1 Tg rat for age-related neurocognitive impairments is fundamental to disentangling the role of HIV-1 viral proteins and comorbidities in neurocognitive function.

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McLauriin, K. A., Li, H., Ritchie, A., Booze, R. M., Mactutus, C. F.. 2026-04-08. IMPAIRED BRIDGING OF TEMPORAL DISCONTINUITIES IN OLDER ADULT HIV-1 TG RATS. https://doi.org/10.64898/2026.04.06.716768

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