Infusion of human embryonic kidney cell line conditioned medium reverses kainic acid induced hippocampal damage in mice

Dhanushkodi, Anandh; Venugopal, Chaitra; Bevinahal, Pradeep Kumar K.; Kiranmai, S.; Trichur, Raju R.; Talakad, Sathyaprabha N.; Bhonde, Ramesh

doi:10.1016/j.jcyt.2014.07.001

Cited by 8 publications

(6 citation statements)

References 27 publications

(34 reference statements)

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“…43,44 In kainic acid induced hippocampal damaged mice, HEK-CM treatment showed significant increase in neuro-protection and improvement of hippocampal cognitive function. 45,46 Further, previous studies in aged animals also showed that EE prevents age-associated impairments in spatial learning and cognition. 26,47…”

Section: Spatial Learning and Memorymentioning

confidence: 88%

Section: Cognitionmentioning

confidence: 99%

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Exploring potential strategies to enhance memory and cognition in aging mice

Bhat M,

M G,

Dhanushkodi

et al. 2024

F1000Res

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Background Aging population is rapidly expanding worldwide, and age-related cognitive impairments prove detrimental for achieving a better productive and quality of life. Lack of effective therapies for age-related cognitive impairment focuses attention on developing preventive strategies, such as nutritional interventions, cell therapies and environmental manipulations. The objective of the present study was to explore the comparative benefits of potential memory-enhancing strategies like supplementation of choline (Ch) and docosahexaenoic acid (DHA) or administration of human embryonic kidney stem cell conditioned media (HEK-CM) or exposure to environmental enrichment (EE), that attenuates cognitive impairments in aging mice. Methods Twelve-month-old CF1 male mice were subdivided [n=6/group] into normal aging control (NAC), saline vehicle control (SVC), Ch-DHA, EE, heat-inactivated HEK-CM (HIHEK-CM) and HEK-CM groups. Spatial working and reference memory were assessed using an eight-arm radial maze test and cognition using a novel object recognition test (NORT). Results Spatial memory and cognition were decreased in normal aging mice. Aged mice exposed to dietary Ch-DHA or HEK-CM showed significant enhancement in spatial learning tasks, memory and cognition compared to the same in age-matched NAC mice. Ch-DHA and HEK-CM treated mice committed significantly lesser reference memory errors and attained a higher percentage of correct choices in spatial learning and memory tasks. Moreover, on testing for cognition in NORT, significantly higher number of visits to the novel object was observed in Ch-DHA supplemented and HEK-CM administered aging mice whereas HEK-CM and EE mice groups showed significantly greater number of visits to familiar object, when compared to same in age-matched NAC and HIHEK-CM groups, respectively. Conclusion Supplementation of Ch-DHA and HEK-CM treatment strategies have a higher potential [~ 20—30%] for enhancing spatial learning, memory and cognition in normal aged mice, whereas exposure to EE seems to enhance only their short-term memory.

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Section: Spatial Learning and Memorymentioning

confidence: 88%

Section: Cognitionmentioning

confidence: 99%

Exploring potential strategies to enhance memory and cognition in aging mice

Bhat M,

M G,

Dhanushkodi

et al. 2024

F1000Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…44,45 In kainic acid induced hippocampal damaged mice, HEK-CM treatment showed significant increase in neuro-protection and improvement of hippocampal cognitive function. 46 Further, previous studies in aged animals also showed that environmental enrichment prevents age-associated impairments in spatial learning and cognition. 26,47…”

Section: Spatial Learning and Memorymentioning

confidence: 94%

“…Normal mice that received HEK-CM also showed higher preference for novel object as compared with familiar objects. 46 Combined supplementation of nutrients like Ch and DHA after perinatal brain injury in mice showed a substantial preference for the novel object when subjected to NORT, indicating that recognition memory after brain injury was improved by the supplementation of DHA and Ch. 48 Aged mice, exposed to standard environment rather than EE, were able to discriminate between familiar and novel Human embryonic kidney stem cell conditioned media (HEK-CM) and choline-docosahexaenoic acid (Ch-DHA) mice vs heat inactivated HEK-CM (HIHEK-CM) or normal ageing control (NAC) mice respectively made significantly greater number of visits to novel object.…”

Section: Cognitionmentioning

confidence: 99%

Exploring potential strategies to enhance memory and cognition in aging mice

Dhanushkodi

et al. 2023

F1000Res

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Background: Aging population is rapidly expanding worldwide, and age-related cognitive impairments prove detrimental for achieving a better productive and quality of life. Lack of effective therapies for age-related cognitive impairment focuses attention on developing preventive strategies, such as nutritional interventions, cell therapies and environmental manipulations. The objective of the present study was to explore the comparative benefits of potential memory-enhancing strategies like supplementation of choline (Ch) and docosahexaenoic acid (DHA) or administration of human embryonic kidney stem cell conditioned media (HEK-CM) or exposure to environmental enrichment (EE), that attenuates cognitive impairments in aging mice. Methods: 12-month-old CF1 male mice were subdivided [n=6/group] into normal aging control (NAC), saline vehicle control (SVC), Ch-DHA, EE, heat-inactivated HEK-CM (HIHEK-CM) and HEK-CM mice. Spatial working and reference memory were assessed using an eight-arm radial maze test and cognition using a novel object recognition test (NORT). Results: Spatial memory and cognition were decreased in normal aging mice. Aged mice exposed to dietary Ch-DHA or HEK-CM showed significant enhancement in spatial learning tasks, memory and cognition compared to the same in age-matched NAC mice. Ch-DHA and HEK-CM treated mice committed significantly lesser reference memory errors and attained a higher percentage of correct choices in spatial learning and memory tasks. Moreover, on testing for cognition in NORT, significantly higher number of visits to the novel object was observed in Ch-DHA supplemented and HEK-CM administered aging mice whereas HEK-CM and EE mice groups showed significantly greater number of visits to familiar object, when compared to same in age-matched NAC and HIHEK-CM groups, respectively. Conclusion: Supplementation of Ch-DHA and HEK-CM treatment strategies have a higher potential [~ 20—30%] for enhancing spatial learning, memory and cognition in normal aged mice, whereas exposure to EE seems to enhance only their short-term memory.

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“…The neuroprotective ability of adipose stromal cell conditioned medium was partially attributed to the presence of insulin‐like growth factor‐1 and BDNF (Wei et al ., ). We have recently demonstrated that intravenous infusion of secretome derived from human embryonic kidney (HEK) cell culture into hippocampus‐damaged mice could restore the neuronal density and cognitive functions, equivalent to that of HEK cell transplantation (Dhanushkodi et al ., ), suggesting that the growth factors present in the secretome could be adequate to thwart hippocampal neurodegeneration.…”

Section: Stem Cell Secretome: a Versatile Multifunctional Drugstorementioning

confidence: 99%

Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies

Venugopal

Chandanala

Prasad

et al. 2015

J Tissue Eng Regen Med

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Increase in life expectancy has put neurodegenerative diseases on the rise. Amongst these, degenerative diseases involving hippocampus like Alzheimer's disease (AD) and temporal lobe epilepsy (TLE) are ranked higher as it is vulnerable to excitotoxicity induced neuronal dysfunction and death resulting in cognitive impairment. Modern medicines have not succeeded in halting the progression of these diseases rendering them incurable and often fatal. Under such scenario, regenerative studies employing stem cells or their by-products in animal models of AD and TLE have yielded encourageing results. This review focuses on the distinct cell types, such as hippocampal cell lines, neural precursor cells, embryonic stem cells derived neural precursor cells, induced pluripotent stem cells, induced neurons and mesenchymal stem cells, which can be employed to rescue hippocampal functions in neurodegenerative diseases like AD and TLE. Besides, the divergent mechanisms through which cell based therapy confer neuroprotection, current impediments and possible improvements in stem cell transplantation strategies are discussed. Authors are aware of the voluminous literature available on this issue and have made a sincere attempt to put forth the current status of research in the field of cell based therapy concurrently discussing the promise it holds for combating neurodegenerative diseases like AD and TLE in the near future. Copyright © 2015 John Wiley & Sons, Ltd.

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Infusion of human embryonic kidney cell line conditioned medium reverses kainic acid induced hippocampal damage in mice

Cited by 8 publications

References 27 publications

Exploring potential strategies to enhance memory and cognition in aging mice

Exploring potential strategies to enhance memory and cognition in aging mice

Exploring potential strategies to enhance memory and cognition in aging mice

Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies

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