Cannabidiol Ameliorates Cognitive Function via Regulation of IL-33 and TREM2 Upregulation in a Murine Model of Alzheimer’s Disease

Skrobas

2022

J Educ Health Sport

Introduction and purpose. Dementia is a major public health problem. Alzheimer's disease (AD) accounts for 60% of dementia cases. However, AD is currently considered as an incurable disorder and the only few drugs available for its treatment are mostly symptomatic. In the quest for novel drugs for this devastating disease, cannabidiol (CBD) has been recently gaining attention due to its multiple properties. The aim of this review article was to summarize findings on the effect of CBD on AD with a focus on molecular mechanisms of CBD's action and therapeutic effects which it exerts. The review was performed based on available literature on the PubMed platform by entering key words: Alzheimer's disease, cannabidiol.

Section: In Vivo Studies On Cbd In Alzheimer's Diseasementioning

confidence: 85%

Section: In Vivo Studies On Cbd In Alzheimer's Diseasementioning

confidence: 88%

Cannabidiol in the treatment and prevention of Alzheimer’s disease – a comprehensive overview of in vitro and in vivo studies

Skrobas

2022

J Educ Health Sport

“…Surgery/anesthesia did not affect the freezing time of dNCR mice in the tone test, which is consistent with previous studies [ 16 , 20 ] and indicated that surgery/anesthesia did not impair hippocampus-independent memory. In AD mouse [ 18 , 30 ] and RNS rat [ 12 ] models, IL-33 has been proven to improve cognitive defects via anti-inflammation. Conversely, bilateral intrahippocampal injection of IL-33 (400 ng) induced IL-1β overexpression by microglia cells and cognitive impairment in mice [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice

Zhao

Shi

et al. 2022

Brain Sciences

Delayed neurocognitive recovery (dNCR), a postoperative complication that occurs in elderly patients, still lacks effective treatment. Interleukin-33 (IL-33) has been proved to modulate neuroinflammation and synaptic plasticity, among other effects, but the role of IL-33 in dNCR is not clear. We established a dNCR model in aged mice by laparotomy under sevoflurane anesthesia. Cognition was evaluated by Morris water maze (MWM) and fear conditioning test (FCT). Immunofluorescence was used to detect the density of IL-33 and glial fibrillary acidic protein (GFAP) co-localization, ionized calcium-binding adapter molecule 1, vesicular glutamate transporter 1 (vGlut1) and postsynaptic density protein-95 (PSD95) co-localization in the hippocampus. IL-33, GFAP, vGlut1 and PSD95 were tested by Western blotting. Enzyme-linked immunosorbent assay was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-10. Surgery/anesthesia reduced the level of IL-33 in the hippocampus. Intraperitoneal injection of 200 ng IL-33 per mouse significantly decreased the latency to the platform and increased the number of platform crossings and the target quadrant dwell time in MWM, while increasing the freezing time in the context test of FCT. Furthermore, IL-33 inhibited microglial activation and the release of TNF-α and IL-1β while upregulating the markers of excitatory synapses vGlut1 and PSD95. Our findings indicated that IL-33 improved cognition by inhibiting the hippocampal inflammatory response and upregulating the number of excitatory synapses. Therefore, IL-33 is a potential drug for the treatment of dNCR.

“…It has been proposed that CBD may have neuroprotective effects via its impact on peroxisome proliferator-activated receptor gamma and subsequently Aβ clearance [168]. A recent translational study suggested improvements in cognition in familial AD mice with CBD due to upregulation of interleukin 33 and triggering receptors expressed on myeloid cells 2 (TREM2), which play a role in phagocytosis and reduction of inflammation associated with plaque formation [169]. Several small case series have suggested utility of dronabinol for nocturnal agitation in people with dementia [170] and for dream enactment behavior [171], but controlled trials have yet to occur.…”

Section: Cannabidiol/tetrahydrocannabinolmentioning

confidence: 99%

Impact of Pharmacotherapy on Insomnia in Patients with Alzheimer’s Disease

Roland

Bliwise

2021

Drugs Aging

Insomnia is a pervasive sleep disorder affecting numerous patients across diverse demographical populations and comorbid disease states. Contributing factors are often a complex interaction of biological, psychological, and social components, requiring a multifaceted approach in terms of both diagnosis and management. In the setting of Alzheimer's disease, insomnia is an even more complicated issue, with a higher overall prevalence than in the general population, greater complexity of contributing etiologies, and differences in diagnosis (at times based on caregiver observation of sleep disruption rather than subjective complaints by the individual with the disorder), and requiring more discretion in terms of treatment, particularly in regard to adverse effect profile concerns. There also is growing evidence of the bidirectional nature of sleep disruption and Alzheimer's disease, with insomnia potentially contributing to disease progression, making the condition even more paramount to address. The objective of this review was to provide the clinician with an overview of treatment strategies that may have value in the treatment of disturbed sleep in Alzheimer's disease. Nonpharmacological approaches to treatment should be exhausted foremost; however, pharmacotherapy may be needed in certain clinical scenarios, which can be a challenge for clinicians given the paucity of evidence and guidelines for treatment in the subpopulation of Alzheimer's disease. Agents such as sedating antidepressants, melatonin, and site-specific γ-aminobutyric acid agonists are often employed based on historical usage but are not necessarily supported by high-quality trials. Newer agents such as dual orexin receptor antagonists have demonstrated some promise but still need further evaluation.