Increasing dietary choline attenuates spatial memory deficits resulting from exposure to the chemotherapeutic agents cyclophosphamide and doxorubicin

2021 ◽  
pp. 026988112110297
Author(s):  
Bethany E Johns ◽  
Melissa Ficken ◽  
Melanie E Engberg ◽  
Lynn Wecker ◽  
Rex M Philpot
Keyword(s):  
Spatial Memory ◽  
Cognitive Deficits ◽  
Memory Deficits ◽  
Chemotherapeutic Agents ◽  
Standard Diet ◽  
Cognitive Domains ◽  
Intravenous Injections ◽  
Impaired Memory ◽  
Dietary Choline

Background: Choline supplementation (+Ch) improves cognitive function in impaired animals and humans. Chemotherapy-related cognitive deficits (CRCDs) occur in cancer patients, and these deficits persist following treatment, adversely impacting quality of life. To date, there are no approved treatments for this condition. Aim: Because +Ch improves impaired memory, it was of interest to determine whether +Ch can attenuate spatial memory deficits induced by the chemotherapeutic agents doxorubicin (DOX) and cyclophosphamide (CYP). Methods: Female BALB/C mice, 64 days of age, were trained in the Morris water maze and baseline performance determined on day 15. Following baseline assessment, mice were placed on +Ch diet (2.0% Ch) or remained on standard diet (0.12% Ch). Mice received intravenous injections of DOX (2.5 mg/kg) and CYP (25 mg/kg), or equivalent volumes of saline (0.9% NaCl), on days 16, 23, 30, and 37, and spatial memory was assessed weekly from day 22 to 71. Results: DOX and CYP produced a prolonged impairment in spatial memory as indicated by an increased latency to the correct zone ( p < 0.05), and a decrease in time in the correct zone ( p < 0.05), % of total swim distance in the correct zone ( p < 0.05) and % entries to the correct zone ( p < 0.05). These effects were attenuated by +Ch. Conclusion: Although it remains to be determined whether this effect extends to other cognitive domains and whether +Ch is prophylactic or therapeutic, these findings suggest that +Ch may be an effective intervention for CRCDs.

Chemotherapy and cognitive deficits: Mechanisms, findings, and potential interventions

2007 ◽  
Vol 5 (3) ◽  
pp. 273-280 ◽  
Author(s):  
Christian J. Nelson ◽  
Nina Nandy ◽  
Andrew J. Roth
Keyword(s):  
Quality Of Life ◽  
Cognitive Deficits ◽  
Verbal Memory ◽  
Behavioral Therapy ◽  
Chemotherapeutic Agents ◽  
Contributing Factors ◽  
Cognitive Domains ◽  
Human Erythropoietin ◽  
Direct Injury

“Chemobrain” is the phenomenon of cognitive decline some patients may experience after chemotherapy. Current research indicates the cognitive domains that may be most impacted by chemotherapeutic agents are visual and verbal memory, attention, and psychomotor functioning. These cognitive deficits can have an effect on a patient's ability to make informed treatment decisions, pursue occupational or academic pursuits, and his or her overall quality of life. The potential mechanisms that cause this disruption remain largely unknown, although contributing factors could be vascular injury and oxidative damage, inflammation, direct injury to neurons, autoimmune responses, chemotherapy-induced anemia, and the presence of the apolipoprotein E ε4 (APOE ε 4) gene. Interventions to help alleviate the symptoms of chemobrain could include nonpharmacologic treatment such as antioxidants and cognitive-behavioral therapy. In addition, patients may benefit from pharmacologic treatment such as recombinant human erythropoietin and psychostimulant drugs such as methylphenidate. It is important to note that the proposed therapeutics treat the symptoms of chemobrain based on the hypothesized mechanisms. Therefore, a detailed understanding of the mechanisms that cause chemobrain, as well as a comprehension of what specific cognitive domains are impacted, is crucial in developing more specific treatments to improve patients' cognitive functioning and overall quality of life.

scholarly journals Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

2020 ◽  
Author(s):  
Pengbo Shi ◽  
Zhaosu Li ◽  
Xing Xu ◽  
Jiaxun Nie ◽  
Dekang Liu ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Cognitive Deficits ◽  
Glutamate Uptake ◽  
Cognitive Disorders ◽  
Memory Deficits ◽  
Therapeutic Interventions ◽  
Therapeutic Effects ◽  
Non Invasive ◽  
The Brain

ABSTRACTMethamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a key target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.

scholarly journals Cognitive and Functional Outcome After Out of Hospital Cardiac Arrest

2011 ◽  
Vol 17 (2) ◽  
pp. 364-368 ◽  
Author(s):  
Michael P. Alexander ◽  
Ginette Lafleche ◽  
David Schnyer ◽  
Chun Lim ◽  
Mieke Verfaellie
Keyword(s):  
Cardiac Arrest ◽  
Cognitive Deficits ◽  
Functional Outcomes ◽  
Memory Deficits ◽  
Cognitive Domains ◽  
Middle Range ◽  
High Prevalence ◽  
Prevalence Of Depression ◽  
Coronary Care ◽  
Hospital Cardiac Arrest

AbstractThe nature of residual cognitive deficits after out of hospital cardiac arrest (OHCA) is incompletely described and has never been defined against a cardiac control (CC) group. The objective of this study is to examine neuropsychological outcomes 3 months after OHCA in patients in a “middle range” of acute severity. Thirty prospective OHCA admissions with coma >1 day and responsive but confused at 1 week, and 30 non-OHCA coronary care admissions were administered standard tests in five cognitive domains. OHCA subjects fell into two deficit profiles. One group (N= 20) had mild memory deficits and borderline psychomotor deficits compared to the CC group; 40% had returned to work. The other group (N= 10) had severe impairments in all domains. Coma duration was associated with group. Neither group had a high prevalence of depression. For most patients within the “middle range” of acute severity of OHCA, cognitive and functional outcomes at 3 months were encouraging. (JINS, 2011,17, 364–368)

scholarly journals Unbalanced dendritic inhibition of CA1 neurons drives spatial-memory deficits in the Ts2Cje Down syndrome model

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sergio Valbuena ◽  
Álvaro García ◽  
Wilfrid Mazier ◽  
Ana V. Paternain ◽  
Juan Lerma
Keyword(s):  
Down Syndrome ◽  
Spatial Memory ◽  
Cognitive Deficits ◽  
Pyramidal Cells ◽  
Memory Deficits ◽  
Synaptic Inhibition ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Cells ◽  
Encoding Gene ◽  
Inhibitory Tone

Abstract Overinhibition is assumed one of the main causes of cognitive deficits (e.g. memory impairment) in mouse models of Down syndrome (DS). Yet the mechanisms that drive such exaggerated synaptic inhibition and their behavioral effects remain unclear. Here we report the existence of bidirectional alterations to the synaptic inhibition on CA1 pyramidal cells in the Ts2Cje mouse model of DS which are associated to impaired spatial memory. Furthermore, we identify triplication of the kainate receptor (KAR) encoding gene Grik1 as the cause of these phenotypes. Normalization of Grik1 dosage in Ts2Cje mice specifically restored spatial memory and reversed the bidirectional alterations to CA1 inhibition, but not the changes in synaptic plasticity or the other behavioral modifications observed. We propose that modified information gating caused by disturbed inhibitory tone rather than generalized overinhibition underlies some of the characteristic cognitive deficits in DS.

scholarly journals Dietary Choline Protects Against Cognitive Decline After Surgery in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Sara V. Maurer ◽  
Cuicui Kong ◽  
Niccolò Terrando ◽  
Christina L. Williams
Keyword(s):  
Cognitive Deficits ◽  
Tibial Fracture ◽  
Dietary Intervention ◽  
Granule Cells ◽  
Subgranular Zone ◽  
Common Complication ◽  
Impaired Memory ◽  
Post Surgery ◽  
Dietary Choline ◽  
Fracture Surgery

Perioperative neurocognitive disorders (PNDs) are a common complication following procedures such as orthopedic surgery. Using a mouse model of tibial fracture and repair surgery, we have previously shown an increase in neuroinflammation and hippocampal-dependent cognitive deficits. These changes were ameliorated with the addition of a cholinergic agonist. Here, we sought to examine the effects of a high-choline diet for 3 weeks prior to tibial fracture surgery. We evaluated memory using novel object recognition (NOR) as well as young neurons and glial cell morphology at 1 day and 2 weeks post-surgery. At both time points, tibial fracture impaired NOR performance, and dietary choline rescued these impairments. Astrocytic density and hilar granule cells increased 1 day after tibial fracture, and these increases were partially blunted by dietary choline. An increase in young neurons in the subgranular zone of the dentate gyrus was found 2 weeks after tibial fracture. This increase was partially blunted by choline supplementation. This suggests that shortly after tibial fracture, hippocampal reorganization is a possible mechanism for acute impaired memory. These findings together suggest that non-pharmaceutical approaches, such as pre-surgical dietary intervention with choline, may be able to prevent PNDs.

scholarly journals Targeting aberrant dendritic integration to treat cognitive comorbidities of epilepsy

2020 ◽  
Author(s):  
Nicola Masala ◽  
Martin Pofahl ◽  
Andre Nathan Haubrich ◽  
Negar Nikbakht ◽  
Kirsten Bohmbach ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Cognitive Deficits ◽  
Memory Deficits ◽  
Spatial Coding ◽  
Dendritic Integration ◽  
Two Photon ◽  
Dendritic Spikes ◽  
Channel Dependent ◽  
Dependent Mechanism

AbstractMemory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding, and deficits in spatial memory.Two-photon glutamate uncaging experiments revealed that the mechanisms constraining the generation of Na+ spikes in hippocampal 1st order pyramidal cell dendrites are profoundly degraded in experimental epilepsy. This phenomenon was reversed by selectively blocking Nav1.3 sodium channels. In-vivo two-photon imaging revealed that hippocampal spatial representations were less precise in epileptic mice. Blocking Nav1.3 channels significantly improved the precision of spatial coding, and reversed hippocampal memory deficits.Thus, a dendritic channelopathy may underlie cognitive deficits in epilepsy and targeting it pharmacologically may constitute a new avenue to enhance cognition.One Sentence SummaryImpaired input computations via aberrant dendritic spikes in chronic epilepsy degrade neuronal place codes and spatial memory

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla
Keyword(s):  
Adverse Effects ◽  
Anticancer Agents ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Normal Cells ◽  
Normal Tissues ◽  
Organ Specific ◽  
Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

scholarly journals Cognitive training interventions for dementia and mild cognitive impairment in Parkinson’s disease - A cochrane review summary with commentary

2021 ◽  
pp. 1-3
Author(s):  
Tobias Loetscher
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Training ◽  
Verbal Memory ◽  
Cognitive Impairments ◽  
Cochrane Review ◽  
Cognitive Domains ◽  
Training Interventions

BACKGROUND: The majority of people living with Parkinson’s disease will develop impairments in cognition. These impairments are associated with a reduced quality of life. OBJECTIVE: The Cochrane Review aimed to investigate whether cognitive training improves cognition in people with Parkinson’s disease and mild cognitive impairments or dementia. METHODS: A Cochrane Review by Orgeta et al. was summarized with comments. RESULTS: The review included seven studies with a total of 225 participants. There was no evidence for improvements in global cognition when cognitive training was compared to control conditions. Observed improvements in attention and verbal memory measures after cognitive training could not be confirmed in a subsequent sensitivity analysis. There was no evidence for benefits in other cognitive domains or quality of life measures. The certainty of the evidence was low for all comparisons. CONCLUSIONS: The effectiveness of cognitive training for people with Parkinson’s disease and cognitive impairments remains inconclusive. There is a pressing need for adequately powered trials with higher methodological quality.

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