Biology subjects

Noback, M.

Publications and source records attributed to Noback, M..

3 recordsLinked to original sources

bioRxiv2025

Chronic nicotine treatment enhanced cognition and reduced neuroinflammation in the gp120 transgenic mouse model of neuroHIV

RationaleAntiretroviral development has improved the longevity of people with HIV (PWH), but many experience impaired cognition potentially due to neuroinflammation. PWH smoke cigarettes at higher rates than the general population, possibly for self-medication given cognitive-enhancing and anti-inflammatory properties of nicotine, the primary psychoactive ingredient cigarette smoke. We hypothesized that chronic nicotine would improve cognition in a mouse model of HIV, gp120 transgenic (Tg) mice, and reduce neuroinflammation. MethodsMale and female gp120-Tg mice (n=64) and littermate controls (n=67) were operantly trained then tested for effortful motivation in the progressive ratio breakpoint task (PRBT). Mice were counter-balanced into three groups for saline or nicotine minipump implantation (0, 14 or 40 mg/kg/day) then retested 25 days later in the PRBT, probabilistic reversal learning task (PRLT - reinforcement learning and cognitive flexibility), and Iowa Gambling Task (IGT - risk-based decision-making), with a subset tested for neuroinflammation (Iba-1 levels). ResultsGp120-Tg mice exhibited worse PRLT performance, attenuated by nicotine. Furthermore, nicotine selectively optimized their response strategies in the PRLT and IGT, increasing loss sensitivity, shifting animals towards "safer" responses. No motivation effects were observed. Nicotine also reduced Iba-1 expression, suggesting that its cognitive-enhancing effects may relate to reduced neuroinflammation. ConclusionGp120-Tg mice exhibited deficits in the PRLT, which are attenuated by chronic nicotine. Furthermore, nicotine improved reinforcement learning and risky decision-making supporting its therapeutic potential for cognitive deficits in PWH, possibly via reducing neuroinflammation. With potential negative consequences of long-term nicotine use, future studies should determine its mechanism of action to develop more targeted therapeutics.

neuroscience↗

bioRxiv2021

Post-weaning social isolation modulates reward-seeking behavior in a sex-specific manner in mice

Social isolation is a growing concern in public health. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of adolescent social isolation (SI) and compared performance of isolated and group-housed mice on touchscreen-based continuous performance test (CPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI increased sensitivity in the CPT in male mice and had no effect in female mice. The increase in sensitivity was consistent across time bins within the 45-minute testing session and there were no SI effects on reaction times or reward retrieval latencies. A possible confound for performance in the CPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both FR and PR schedules of reinforcement and found that male SI mice earned significantly more reinforcers on FR schedules of reinforcement and had higher breakpoints on PR schedules compared to their group-housed littermates. SI had no effect on FR or PR performance in female mice. These data indicate that SI during adolescence has striking, sex-specific effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

neuroscience↗

bioRxiv2020

Post-weaning social isolation increases ΔFosB/FosB protein expression in the prefrontal cortex and hippocampus in mice

Social isolation is a growing public health concern across the lifespan. Specifically, isolation early in life, during critical periods of brain development, increases the risk of psychiatric disorders later in life. Previous studies of isolation models in mice have shown distinct neurological abnormalities in various regions of the brain, but the mechanism linking the experience of isolation to these phenotypes is unclear. In this study, we show that {Delta}FosB, a long-lived transcription factor associated with chronic stress responses and drug-induced neuroplasticity, is upregulated in the medial prefrontal cortex and hippocampus of adult C57BL/6J mice isolated for two weeks post-weaning. Additionally, a related transcription factor, FosB, is also increased in the medial prefrontal cortex in socially isolated females. These results show that short-term isolation during the critical post-weaning period has long-lasting and sex-dependent effects on gene expression in brain.

neuroscience↗