Tanshinone IIA Alleviates CCL2-Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV-Associated Neurocognitive Disorder

Chemokine CC motif ligand 2 (CCL2) is one of the most recognized proinflammatory chemokines, and the expression of CCL2 in the cerebrospinal fluid of patients infected with HIV-1 is significantly higher than that of healthy people. As such, it is seen as an important cause of HIV-associated neurocognitive disorder (HAND). Our previous investigation has confirmed the pathological role of CCL2 in mediating brain damage leading to cognitive dysfunction. Currently, however, research on therapeutic drugs for the central nervous system targeting CCL2 is very limited. Our present study used brain stereotactic technology to induce cognitive impairment in rats by injecting CCL2 (5 ng) into the bilateral hippocampus. To investigate the protective effect and mechanism of Tanshinone IIA (25, 50, 75 mg/kg/d) on CCL2-induced learning memory and cognitive impairment in rats, we performed the Morris water maze (MWM) and novel object recognition tests (NORT) on the rats. The results showed that Tanshinone IIA significantly alleviated CCL2-induced learning memory and cognitive dysfunction. Further studies on the hippocampal tissue of the rats revealed that Tanshinone IIA treatment significantly increased the activity of SOD and GSH-Px while the level of MDA decreased compared to the model group. Additionally, the relative expression of apoptosis-associated genes caspase-3, caspase-8, and caspase-9 and inflammation-associated genes IL-1β and IL-6 in Tanshinone IIA-treated rats was lower than that in model rats. Finally, we confirmed hippocampal neuron loss and apoptosis by Nissl staining and TdT-mediated dUTP Nick end labeling (TUNEL). Taken together, these data imply that Tanshinone IIA can ameliorate CCL2-induced learning memory and cognitive impairment by impacting oxidative stress, inflammation, and apoptosis. Tanshinone IIA may be a potential therapeutic agent for the treatment of HAND.

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Corrigendum to “Tanshinone IIA Alleviates CCL2-Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV-Associated Neurocognitive Disorder”

BioMed Research International ◽

10.1155/2020/5834542 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3

Author(s):

Yuan-jun Liao ◽

Jian-min Chen ◽

Jiang-yi Long ◽

Yi-jun Zhou ◽

Bing-yu Liang ◽

...

Keyword(s):

Therapeutic Approach ◽

Tanshinone Iia ◽

Neurocognitive Disorder ◽

Hiv Associated Neurocognitive Disorder ◽

Cognition Impairment

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Tryptophan, Neurodegeneration and HIV-Associated Neurocognitive Disorder

International Journal of Tryptophan Research ◽

10.4137/ijtr.s4321 ◽

2010 ◽

Vol 3 ◽

pp. IJTR.S4321 ◽

Cited By ~ 33

Author(s):

Nicholas W.S. Davies ◽

Gilles Guillemin ◽

Bruce J. Brew

Keyword(s):

Neurodegenerative Disease ◽

Differential Expression ◽

Inflammatory Cells ◽

Kynurenine Pathway ◽

Motor Neurone ◽

Neurocognitive Disorder ◽

Pathogenetic Role ◽

Hiv Associated Neurocognitive Disorder ◽

The Brain

This review presents an up-to-date assessment of the role of the tryptophan metabolic and catabolic pathways in neurodegenerative disease and HIV-associated neurocognitive disorder. The kynurenine pathway and the effects of each of its enzymes and products are reviewed. The differential expression of the kynurenine pathway in cells within the brain, including inflammatory cells, is explored given the increasing recognition of the importance of inflammation in neurodegenerative disease. An overview of common mechanisms of neurodegeneration is presented before a review and discussion of the evidence for a pathogenetic role of the kynurenine pathway in Alzheimer's disease, HIV-associated neurocognitive disorder, Huntington's disease, motor neurone disease, and Parkinson's disease.

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Corrigendum: Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis

Frontiers in Neuroscience ◽

10.3389/fnins.2021.825158 ◽

2022 ◽

Vol 15 ◽

Author(s):

Huaqian Dong ◽

Xiang Ye ◽

Li Zhong ◽

Jinhong Xu ◽

Jinhua Qiu ◽

...

Keyword(s):

Neuronal Apoptosis ◽

Neurocognitive Disorder ◽

Hiv Associated Neurocognitive Disorder ◽

Hiv 1

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Distinguishing cognitive impairment from HIV-associated neurocognitive disorder versus substance use?

AIDS ◽

10.1097/qad.0000000000002292 ◽

2019 ◽

Vol 33 (12) ◽

pp. 1943-1944 ◽

Cited By ~ 2

Author(s):

Bruce J. Brew ◽

Justin McArthur

Keyword(s):

Substance Use ◽

Cognitive Impairment ◽

Neurocognitive Disorder ◽

Hiv Associated Neurocognitive Disorder

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Risk Factors and Pathogenesis of HIV-Associated Neurocognitive Disorder: The Role of Host Genetics

International Journal of Molecular Sciences ◽

10.3390/ijms19113594 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3594 ◽

Cited By ~ 12

Author(s):

Ian Olivier ◽

Ramón Cacabelos ◽

Vinogran Naidoo

Keyword(s):

Risk Factors ◽

Immune Response ◽

Human Genetics ◽

Hiv Treatment ◽

Specific Gene ◽

People Living With Hiv ◽

Neurocognitive Disorder ◽

Host Genetics ◽

Hiv Associated Neurocognitive Disorder

Neurocognitive impairments associated with human immunodeficiency virus (HIV) infection remain a considerable health issue for almost half the people living with HIV, despite progress in HIV treatment through combination antiretroviral therapy (cART). The pathogenesis and risk factors of HIV-associated neurocognitive disorder (HAND) are still incompletely understood. This is partly due to the complexity of HAND diagnostics, as phenotypes present with high variability and change over time. Our current understanding is that HIV enters the central nervous system (CNS) during infection, persisting and replicating in resident immune and supporting cells, with the subsequent host immune response and inflammation likely adding to the development of HAND. Differences in host (human) genetics determine, in part, the effectiveness of the immune response and other factors that increase the vulnerability to HAND. This review describes findings from studies investigating the role of human host genetics in the pathogenesis of HAND, including potential risk factors for developing HAND. The similarities and differences between HAND and Alzheimer’s disease are also discussed. While some specific variations in host genes regulating immune responses and neurotransmission have been associated with protection or risk of HAND development, the effects are generally small and findings poorly replicated. Nevertheless, a few specific gene variants appear to affect the risk for developing HAND and aid our understanding of HAND pathogenesis.

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HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction

Journal of Neuroinflammation ◽

10.1186/s12974-019-1640-z ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Xiao-Yu Sun ◽

Teng Zheng ◽

Xiu Yang ◽

Le Liu ◽

Shen-Shen Gao ◽

...

Keyword(s):

Cognitive Impairment ◽

Histone Acetylation ◽

Cognitive Dysfunction ◽

Memory Impairment ◽

Dorsal Hippocampus ◽

Neuroprotective Effect ◽

Memory Deficits ◽

Peripheral Inflammation ◽

Histone Deacetylase 2

Abstract Background Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. Methods Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. Results LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. Conclusions Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

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Prefrontal gating of sensory input differentiates cognitively impaired and unimpaired aging adults with HIV

Brain Communications ◽

10.1093/braincomms/fcaa080 ◽

2020 ◽

Vol 2 (2) ◽

Cited By ~ 2

Author(s):

Rachel K Spooner ◽

Alex I Wiesman ◽

Jennifer O’Neill ◽

Mikki D Schantell ◽

Howard S Fox ◽

...

Keyword(s):

Cognitive Impairment ◽

Neural Activity ◽

Cognitively Impaired ◽

Neurocognitive Disorder ◽

Spontaneous Neural Activity ◽

Somatosensory Input ◽

Hiv Associated Neurocognitive Disorder ◽

Aging Adults ◽

The Impact ◽

Prefrontal Cortices

Abstract Despite effective therapies that have extended the life expectancy of persons living with HIV, 35–70% of these adults still develop some form of cognitive impairment, and with a growing population of aging adults with HIV, the prevalence of these cognitive deficits is likely to increase. The mechanisms underlying these HIV-associated neurocognitive disorders remain poorly understood but are often accelerated by the aging process and accompanied by disturbances in sensory processing, which may contribute to the observed cognitive decline. The goal of the current study was to identify the impact of aging on HIV-related alterations in inhibitory processing and determine whether such alterations are related to cognitive impairment in neuroHIV. We used magnetoencephalographic imaging, advanced time series analysis methods, and a paired-pulse stimulation paradigm to interrogate inhibitory processing in 87 HIV-infected aging adults and 92 demographically matched uninfected controls (22–72 years old). Whole-brain maps linking age and neural indices were computed for each group and compared via Fisher’s Z transformations. Peak voxel time-series data were also extracted from the resulting images to quantify the dynamics of spontaneous neural activity preceding stimulation onset in each group. Whole-brain analyses using the somatosensory gating index, a metric of inhibitory processing and age distinguished impaired adults with HIV from unimpaired HIV-infected adults and controls. Briefly, younger cognitively impaired adults with HIV strongly utilized the prefrontal cortices to gate somatosensory input, and the role of this region in gating was uniquely and significantly modulated by aging only in impaired adults with HIV. Spontaneous neural activity preceding stimulus onset was also significantly elevated in the prefrontal cortices of those with HIV-associated neurocognitive disorder, and this elevation was significantly related to the CD4 nadir across both HIV-infected groups. This is the first study to examine the impact of aging on inhibitory processing in HIV-infected adults with and without cognitive impairment. Our findings suggest that young adults with HIV-associated neurocognitive disorder utilize the prefrontal cortices to gate (i.e. suppress) redundant somatosensory input, and that this capacity uniquely diminishes with advancing age in impaired adults with HIV.

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