HIV-1 Tat protein alters medial prefrontal cortex neuronal activity and recognition memory

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 112075 - 112075

Published: Feb. 22, 2025

Despite advancements in combined antiretroviral therapy, human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) continue to affect 40%-50% of people living with HIV. While neuroimaging studies have revealed HIV-1-induced alterations cortical networks and brain macrostructures, it still remains unclear how individual neurons the medial prefrontal cortex (mPFC) are affected during recognition memory. Using vivo calcium imaging an HIV-1 transactivator transcription (Tat) transgenic mouse model, we examined mPFC neuronal activity a novel object memory task. Our findings show that HIV Tat expression reduces overall Tat(+) mice without altering number activated cells. Moreover, distinct subpopulations up- downmodulated both Tat(-) depending on exploration. Importantly, familiarity-driven increases were disrupted by expression. These enhance our understanding HAND may inform future pharmacological strategies aimed at restoring cognitive function.

Language: Английский

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Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(6), P. e0305868 - e0305868

Published: June 24, 2024

The cannabinoid receptor type 1 (CB R) is a promising therapeutic target for various neurodegenerative diseases, including HIV-1-associated neurocognitive disorder (HAND). However, the potential of CB R by direct activation limited due to its psychoactive side effects. Therefore, research has focused on indirectly activating utilizing positive allosteric modulators (PAMs). Studies have shown that PAMs (ZCZ011 and GAT211) are effective in mouse models Huntington’s disease neuropathic pain, hence, we assess ZCZ011 well-established model neuroHIV. current study investigates effect chronic treatment (14 days) behavioral paradigms endocannabinoid system HIV-1 Tat transgenic female male mice. Chronic (10 mg/kg) did not alter body mass, locomotor activity, or anxiety-like behavior regardless sex genotype. differential effects were noted hot plate latency, motor coordination, recognition memory mice only, with increasing latency improving coordination memory. Only minor no alterations seen related lipids except cerebellum, where was more pronounced Moreover, AEA PEA levels cerebellum positively correlated improved In summary, these findings indicate antinociception, memory, based expression, making options HAND without

Language: Английский

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Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 10, 2024

Abstract The cannabinoid receptor type 1 (CB R) is a promising therapeutic target for various neurodegenerative diseases, including HIV-1-associated neurocognitive disorder (HAND). However, the potential of CB R by direct activation limited due to its psychoactive side effects. Therefore, research has focused on indirectly activating utilizing positive allosteric modulators (PAMs). Studies have shown that PAMs (ZCZ011 and GAT211) are effective in mouse models Huntington’s disease neuropathic pain, hence, we assess ZCZ011 well-established model neuroHIV. current study investigates effect chronic treatment (14 days) behavioral paradigms endocannabinoid system HIV-1 Tat transgenic female male mice. Chronic (10 mg/kg) did not alter body mass, locomotor activity, or anxiety-like behavior regardless sex genotype. differential effects were noted hot plate latency, motor coordination, recognition memory mice only, with increasing latency improving coordination memory. Only minor no alterations seen related lipids except cerebellum, where was more pronounced Moreover, AEA PEA levels cerebellum positively correlated improved In summary, these findings indicate antinociception, memory, based expression, making options HAND without

Language: Английский

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Safety assessment on CBD-rich hemp extract in sub-chronic cross-sex study with rats

Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 495, P. 117218 - 117218

Published: Dec. 25, 2024

Language: Английский

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Effect of Aqueous Extract of Cannabis Sativa Leaf on the Motor Coordination Using the Hanging Wire and Open Field Neurobehavioural Tests in Male Wistar Rats

Journal of Advances in Medicine and Medical Research, Journal Year: 2024, Volume and Issue: 36(6), P. 30 - 41

Published: May 17, 2024

Cannabis sativa is a commonly abused drug especially among younger people in society. The cerebellum located at the back of brain, immediately inferior to occipital and temporal lobes within posterior cranial fossa. study was designed show effect aqueous leave extract cannabis on performance male Wistar rats hanging wire open field neurobehavioural tests. A total 40 were used grouped into five groups. Group I received distilled water for 28 days. II, III, IV V served as low, high, low dose recovery high group respectively. II administered with 10mg/kg body weight III 20mg/kg 28days allowed further days without any administration while administration. represent group. I, sacrificed day after their last intubation. result showed that Sativa did not significantly change outcome test final stage compared initial but E significant decrease time following exposure sativa. We can therefore conclude adversely affect tests carried out.

Language: Английский

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Effect of Aqueous Extract of Cannabis sativa Leaf on the Oxidative Stress Markers in the Brain of Male Wistar Rats

Asian Journal of Applied Chemistry Research, Journal Year: 2024, Volume and Issue: 15(3), P. 53 - 62

Published: June 11, 2024

Cannabis sativa is a commonly abused drug especially among younger people in society. The cerebellum located at the back of brain, immediately inferior to occipital and temporal lobes within posterior cranial fossa. study was designed show effect aqueous leave extract on performance male Wistar rats hanging wire open field neurobehavioural tests. A total 40 were used grouped into five groups. Group received distilled water for 28 days. B, C, D E served as low, high, low dose recovery high group respectively. B administered with 10mg/kg body weight C 20mg/kg 28days allowed further days without any administration while administration. Groups represent A, sacrificed day after their last intubation. result showed that led non-significant increase MDA corresponding significant reduction SOD CAT levels experimental groups compared control A. This pointer presence oxidative stress. It can therefore be concluded there time dependent toxic effects model animals.

Language: Английский

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