Choroid plexus function in neurological homeostasis and disorders: The awakening of the circadian clocks and orexins

Christensen, Jennaya; Li, Crystal; Mychasiuk, Richelle

doi:10.1177/0271678x221082786

Cited by 21 publications

(15 citation statements)

References 119 publications

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“…Frontal/executive function is known to be one of the earliest and most frequently affected neurocognitive domains in patients with PD [35], and it is related to striatal dopamine loss [36–38] and white matter structural alterations [39]. Considering that the CP modulates CSF homeostasis, CP dysfunction, reflected as CP enlargement on brain MRI, could interfere with the effective removal of harmful metabolites from the brain parenchyma through the glymphatic pathway [24, 40], leading to subsequent neurodegeneration. One preclinical study revealed that blocking the glymphatic system accelerated α‐synuclein aggregation in a mouse model of PD [41].…”

Section: Discussionmentioning

confidence: 99%

Association between choroid plexus volume and cognition in Parkinson disease

Jeong

Sunwoo

et al. 2023

Euro J of Neurology

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Background and purposeThe choroid plexus (CP) clears harmful metabolites from the central nervous system as part of the glymphatic system. We investigated the association of CP volume (CPV) with baseline and longitudinal cognitive decline in patients with Parkinson disease (PD).MethodsWe retrospectively reviewed the medical records of 240 patients with newly diagnosed PD who had undergone detailed neuropsychological tests and high‐resolution T1‐weighted structural magnetic resonance imaging during the initial assessment. The CPV of each patient was automatically segmented, and the intracranial volume ratio was used in subsequent analyses. The relationship between CPV and baseline composite scores of each cognitive domain was assessed using multivariate linear regression analyses. A Cox proportional hazards model was used to compare the risk of dementia conversion with CPV.ResultsCPV negatively correlated with composite scores of the frontal/executive function domain (β = −0.375, p = 0.002) after adjusting for age, sex, years of education, and parkinsonian symptom duration. The Cox regression model revealed that a larger CPV was associated with a higher risk of dementia conversion (hazard ratio [HR] = 1.509, p = 0.038), which was no longer significant after adjusting for the composite scores of the frontal/executive function domain. A mediation analysis demonstrated that the effect of CPV on the risk of dementia conversion was completely mediated by frontal/executive function (direct effect: HR = 1.203, p = 0.396; indirect effect: HR = 1.400, p = 0.015).ConclusionsBaseline CPV is associated with baseline frontal/executive function, which subsequently influences dementia conversion risk in patients with PD.

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Section: Discussionmentioning

confidence: 99%

Association between choroid plexus volume and cognition in Parkinson disease

Jeong

Sunwoo

et al. 2023

Euro J of Neurology

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“…That is reviewed by MacAulay et al [ 48 ] with a particular focus on the hypothesis that certain transporters (e.g., NKCC1) may serve as a water channel as well as transport solutes. There has been great interest in how fluid movement in the brain varies diurnally particularly in relation to removal of waste or toxic metabolites (e.g., via the glymphatic system) and it should be noted that the choroid plexus has a circadian rhythm that may impact CSF homeostasis and flow (reviewed in [ 49 ]).…”

Section: Elements Of the Blood-csf Barrier And The Csf And Glymphatic...mentioning

confidence: 99%

A year in review: brain barriers and brain fluids research in 2022

Keep

Jones

Hamilton

et al. 2023

Fluids Barriers CNS

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This aim of this editorial is to highlight progress made in brain barrier and brain fluid research in 2022. It covers studies on the blood-brain, blood-retina and blood-CSF barriers (choroid plexus and meninges), signaling within the neurovascular unit and elements of the brain fluid systems. It further discusses how brain barriers and brain fluid systems are impacted in CNS diseases, their role in disease progression and progress being made in treating such diseases.

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“…Indeed, early symptoms of anxiety and/or depression are predictive of worse functional outcomes in patients with mild TBI (Zahniser et al, 2019). Additionally, sleep–wake disorders are common after TBI, even in patients diagnosed as mild TBI, which can impair daily functions and contribute to neurodegenerative processes that negatively impact long‐term brain health (Christensen et al, 2022; Kaleyias & Kothare, 2022). Prolonged stress can also increase the risk for anxiety, depression, and sleep disorders (McEwen & Akil, 2020).…”

Section: Introductionmentioning

confidence: 99%

Persistent hypersomnia following repetitive mild experimental traumatic brain injury: Roles of chronic stress and sex differences

Portillo

Kim

et al. 2023

J of Neuroscience Research

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Traumatic brain injury (TBI) is often more complicated than a single head injury. An extreme example of this point may be military service members who experience a spectrum of exposures over a prolonged period under stressful conditions. Understanding the effects of complex exposures can inform evaluation and care to prevent persistent symptoms. We designed a longitudinal series of non-invasive procedures in adult mice to evaluate the effects of prolonged mild stress and head injury exposures. We assessed anxiety, depression, and sleep-wake dysfunction as symptoms that impact long-term outcomes after mild TBI. Unpredictable chronic mild stress (UCMS) was generated from a varied sequence of environmental stressors distributed within each of 21 days. Subsequently, mice received a mild blast combined with closed-head mild TBI on 5 days at 24-h intervals. In males and females, UCMS induced anxiety without depressive behavior. A major finding was reproducible sleep-wake dysfunction through 6-to 12-month time points in male mice that received UCMS with repetitive blast plus TBI events, or surprisingly after just UCMS alone. Specifically, male mice exhibited hypersomnia with increased sleep during the active/dark phase and fragmentation of longer wake bouts. Sleep-wake dysfunction was not found with TBI events alone, and hypersomnia was not found in females under any conditions. These results identify prolonged stress and sex differences as important considerations for sleep-wake dysfunction. Furthermore, this reproducible hypersomnia with impaired wakefulness is similar to the excessive daytime sleepiness reported in patients, including patients with TBI, which warrants further clinical screening, care, and treatment development.

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Choroid plexus function in neurological homeostasis and disorders: The awakening of the circadian clocks and orexins

Cited by 21 publications

References 119 publications

Association between choroid plexus volume and cognition in Parkinson disease

Association between choroid plexus volume and cognition in Parkinson disease

A year in review: brain barriers and brain fluids research in 2022

Persistent hypersomnia following repetitive mild experimental traumatic brain injury: Roles of chronic stress and sex differences

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