The Hippocampal Vulnerability to Herpes Simplex Virus Type I Infection: Relevance to Alzheimer’s Disease and Memory Impairment

Yong, Shin Jie; Yong, Min Hooi; Teoh, Seong Lin; Soga, Tomoko; Parhar, Ishwar S.; Chew, Jactty; Lim, Wei Ling

doi:10.3389/fncel.2021.695738

Cited by 23 publications

(13 citation statements)

References 248 publications

(298 reference statements)

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“…These are discussed in more detail below. Viral infections thus appear to be involved in the progression of AD pathology in the brain, opening up a whole new field of research into neurovirological mechanisms for AD [32,33].…”

Section: Below)mentioning

confidence: 99%

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms

Granholm

2023

JCM

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Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many as four out of five patients who sustained COVID-19 will show one or several neurological symptoms that can last months after the infection has run its course. Neurological symptoms are most common in people who are less than 60 years of age, while encephalopathy is more common in those over 60. Biological mechanisms for these neurological symptoms need to be investigated and may include both direct and indirect effects of the virus on the brain and spinal cord. Individuals with Alzheimer’s disease (AD) and related dementia, as well as persons with Down syndrome (DS), are especially vulnerable to COVID-19, but the biological reasons for this are not clear. Investigating the neurological consequences of COVID-19 is an urgent emerging medical need, since close to 700 million people worldwide have now had COVID-19 at least once. It is likely that there will be a new burden on healthcare and the economy dealing with the long-term neurological consequences of severe SARS-CoV-2 infections and long COVID, even in younger generations. Interestingly, neurological symptoms after an acute infection are strikingly similar to the symptoms observed after a mild traumatic brain injury (mTBI) or concussion, including dizziness, balance issues, anosmia, and headaches. The possible convergence of biological pathways involved in both will be discussed. The current review is focused on the most commonly described neurological symptoms, as well as the possible molecular mechanisms involved.

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Section: Below)mentioning

confidence: 99%

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms

Granholm

2023

JCM

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“…S6B-C), indicating that the observed increases in viral infections were unlikely to result from altered cell survival or density. We also tested if astrocytes were more susceptible to herpes simplex virus-1 (HSV-1), a highly neurotropic double-stranded DNA virus increasingly implicated in AD (80)(81)(82). Indeed, ΔNLS astrocytes had increased levels of HSV-1 infection (Fig.…”

Section: Astrocytic Tdp-43 Affects Interferon-inducible Chemokines An...mentioning

confidence: 99%

Astrocytic TDP-43 dysregulation impairs memory by modulating antiviral pathways and interferon-inducible chemokines

Licht-Murava

Meadows

Palaguachi

et al. 2022

Preprint

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TDP-43 pathology is prevalent in dementia but the cell type-specific effects of TDP-43 are not clear and therapeutic strategies to alleviate TDP-43-linked cognitive decline are lacking. We found that patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD) have aberrant TDP-43 accumulation in hippocampal astrocytes. In mouse models, induction of widespread or hippocampus-targeted accumulation in astrocytic TDP-43 caused progressive memory loss and localized changes in antiviral gene expression. These changes were cell-autonomous and correlated with impaired astrocytic defense against infectious viruses. Among the changes, astrocytes had elevated levels of interferon-inducible chemokines and neurons had elevated levels of the corresponding chemokine receptor CXCR3 in presynaptic terminals. CXCR3 stimulation altered presynaptic function and promoted neuronal hyperexcitability, akin to the effects of astrocytic TDP-43, and blockade of CXCR3 reduced this activity. Ablation of CXCR3 also prevented TDP-43-linked memory loss. Thus, astrocytic TDP-43 dysfunction contributes to cognitive impairment through aberrant chemokine-mediated astrocytic-neuronal interactions.

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“…Recent evidence emphasizes the neurotropism of HSV, and points to brain areas most vulnerable to this infection, such as the hippocampal region, a critical area for episodic memory [40]. In addition, a recent study reports that early imaging markers of Alzheimer's disease such as microstructural alterations in para-hippocampal regions, and lower hippocampal volume, are more frequent in older adults with high anti-HSV 1 IgG titers.…”

Section: Herpesviridaementioning

confidence: 99%

Infectious diseases and cognition: do we have to worry?

et al. 2022

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Objectives Age-related physiological changes, particularly immune system decline, may contribute to greater vulnerability to infectious diseases in older individuals. A growing body of evidence shows that both, acute, and chronic infections may be accompanied by cognitive disturbances as part of their manifestations. Given the importance of cognition in aging trajectories, the objective of this article was to review current knowledge on cognitive outcomes of infectious diseases in older adults, and to emphasize the importance of considering cognition as a domain of interest in its own rights in these diseases. Methods A MEDLINE/PubMed database search was conducted to identify articles reporting cognitive impairment associated with various severe acute infections and specific chronic infectious conditions such as human immune deficiency virus, the herpes virus family, hepatitis C virus, Lyme borreliosis, Helicobacter pylori, periodontitis, and emerging pathogens like SARS-CoV-2, as well as potentially preventive strategies like vaccination. Results/ Conclusions Taken together, the studies examined in the present review emphasize that numerous acute and chronic infectious diseases share mechanisms that, when added to specific risk factors frequently found in older persons, contribute to considerably increase the risk of cognitive outcomes such as cognitive decline and dementia. This review may help to appreciate the role that infectious diseases play in cognitive trajectories and thus promote further investigation on the topic.

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The Hippocampal Vulnerability to Herpes Simplex Virus Type I Infection: Relevance to Alzheimer’s Disease and Memory Impairment

Cited by 23 publications

References 248 publications

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms

Astrocytic TDP-43 dysregulation impairs memory by modulating antiviral pathways and interferon-inducible chemokines

Infectious diseases and cognition: do we have to worry?

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