Amantadine attenuates sepsis-induced cognitive dysfunction possibly not through inhibiting toll-like receptor 2

Xing, Wei; Huang, Pinjie; Lu, Yang; Zeng, Weian; Zuo, Zhiyi

doi:10.1007/s00109-018-1631-z

Cited by 24 publications

(25 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neuroinflammation is considered as an underlying pathological process for POCD (Cao et al, 2012;Zhang et al, 2014;Zheng et al, 2017). Our study has shown that amantadine attenuates POCD in young adult rats possibly via maintaining GDNF levels (Rocha et al, 2012;Zhang et al, 2014) and sepsis-induced cognitive dysfunction via inhibiting neuroinflammation in young mice (Xing et al, 2018). However, the effects of amantadine on old animals after surgery have not been reported.…”

Section: Introductionmentioning

confidence: 68%

Amantadine Alleviates Postoperative Cognitive Dysfunction Possibly by Preserving Neurotrophic Factor Expression and Dendritic Arborization in the Hippocampus of Old Rodents

Zhong

et al. 2020

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

ObjectivesAmantadine has been shown to attenuate postoperative learning and memory dysfunction in young adult rats. However, postoperative cognitive dysfunction often occurs in elderly patients. We aimed to determine whether amantadine attenuated postoperative learning and memory dysfunction and whether these effects were associated with improved dendritic arborization in old rodents.MethodsEighteen-month old male C57BL/6J mice or Fischer 344 rats were subjected to right carotid artery exposure (surgery) under isoflurane anesthesia. This age represents an early old stage in rodents. Carotid artery exposure was used to simulate commonly performed carotid endarterectomy in elderly patients. Amantadine was injected intraperitoneally at 25 μg/g once a day for 3 days with the first dose at 15 min before surgery. The animals were tested by Barnes maze and fear conditioning starting one week after the surgery. Hippocampus was harvested for Western blotting and Golgi staining.ResultsSurgery and anesthesia impaired the learning and memory in old mice and rats. Surgery reduced the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), dendritic arborization and spine density in the hippocampus of old rats. These effects were attenuated by amantadine. The effects of amantadine were blocked by intracerebroventricular injection of anti-BDNF antibody or anti-GDNF antibody.ConclusionSurgery and anesthesia impaired learning, memory and dendritic arborization in old rodents that are age relevant to postoperative cognitive dysfunction. These effects may be attenuated by amantadine via preserving the expression of neurotrophic factors.

show abstract

Section: Introductionmentioning

confidence: 68%

Amantadine Alleviates Postoperative Cognitive Dysfunction Possibly by Preserving Neurotrophic Factor Expression and Dendritic Arborization in the Hippocampus of Old Rodents

Zhong

et al. 2020

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, it is difficult to select a primary outcome for sample size estimate in a complex basic science study. Thus, we aimed to have a sample size at least 5 for biochemical analysis and 8 for behavior study based on our experience and sample size for these types of studies in the literature [63,64]. Generation of the heterozygous UQCRC1 +/− mice.…”

Section: Discussionmentioning

confidence: 99%

Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice

Shan

et al. 2019

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

Ubiquinol cytochrome c reductase core protein I (UQCRC1) is a component of the complex III in the respiratory chain. Its biological functions are unknown. Here, we showed that knockout of UQCRC1 led to embryonic lethality. Disrupting one UQCRC1 allele in mice (heterozygous mice) of both sexes did not affect their growth but reduced UQCRC1 mRNA and protein in the brain. These mice had decreased complex III formation, complex III activity and ATP content in the brain at baseline. They developed worsened neurological outcome after brain ischemia/hypoxia or focal brain ischemia compared with wild-type mice. The ischemic cerebral cortex of the heterozygous mice had decreased mitochondrial membrane potential and ATP content as well as increased free radicals. Also, the heterozygous mice performed poorly in the Barnes maze and novel object recognition tests. Finally, UQCRC1 was expressed abundantly in neurons and astrocytes. These results suggest a critical role of UQCRC1 in embryo survival. UQCRC1 may also be important by forming the complex III to maintain normal brain ischemic tolerance, learning and memory.

show abstract

“…One day after the completion of Barnes maze test, mice were subjected to fear conditioning test as we previously described [ 11 , 12 ]. Each mouse was placed into a test chamber wiped with 70% alcohol and exposed to 3 tone-foot shock pairings (tone: 2000 Hz, 85 dB, 30 s; foot shock: 1 mA, 2 s) with an intertrial interval of 1 min in a relatively dark room.…”

Section: Methodsmentioning

confidence: 99%

“…Seven days after surgery, the animals were subjected to Barnes maze in a way we previously described [11,12] to test their spatial learning and memory. Animals were first placed in the middle of a circular platform with 20 equally spaced holes (SD Instruments, San Diego, CA).…”

Section: Barnes Mazementioning

confidence: 99%

A Novel Individual-based Determination of Postoperative Cognitive Dysfunction in Mice

Zhong

Miao

et al. 2020

Aging and disease

Self Cite

View full text Add to dashboard Cite

Postoperative cognitive dysfunction (POCD) is a significant clinical issue. Aging is a risk factor for POCD. It is known that not every patient develops POCD. This situation shall be similar in animals. Determination of POCD is individual-based in humans but group-based in animal studies. This difference prevents effective evaluation of biomarkers and interventions for POCD in preclinical studies. The objective of this study was to determine whether individual animal could be assessed for POCD by a system similar to that for patients. Seven-week old CD1 and 18-month old C57BL/6 male mice were subjected to right carotid arterial exposure under isoflurane anesthesia. Mice were evaluated by Barnes maze and fear conditioning either postsurgery alone or both prior to surgery and post-surgery. Surgery increased the time to identify the target box in Barnes maze when tested one day or 8 days after the training sessions and reduced freezing behavior in fear conditioning test. This phenomenon occurred in 7-week old animals with and without evaluation before the surgery and in 18-month old mice evaluated before and after surgery. Based on the method and criteria used for a human whose cognition was evaluated before and after surgery to assess individual decline of cognition, 7 in 21 mice in the surgical group and 1 in 21 mice in control group of 7-week old mice had cognitive dysfunction. Among 18-month old mice, 13 in 21 mice in the surgical group and 2 in 20 mice in the control group had cognitive dysfunction. The incidence of cognitive dysfunction in mice with surgery was higher than that in control mice no matter whether young adult (P = 0.045) or old mice (P < 0.001) were considered. These results indicate that surgery induces POCD in mice. Individual animal-based assessment can be used to identify animals with POCD.

show abstract

Amantadine attenuates sepsis-induced cognitive dysfunction possibly not through inhibiting toll-like receptor 2

Abstract: Sepsis induces neuroinflammation and cognitive impairment, which were attenuated by amantadine. Toll-like receptors 2 mediates these sepsis effects but may not be the major target for amantadine to reduce these effects.

Cited by 24 publications

References 36 publications

Amantadine Alleviates Postoperative Cognitive Dysfunction Possibly by Preserving Neurotrophic Factor Expression and Dendritic Arborization in the Hippocampus of Old Rodents

Amantadine Alleviates Postoperative Cognitive Dysfunction Possibly by Preserving Neurotrophic Factor Expression and Dendritic Arborization in the Hippocampus of Old Rodents

Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice

A Novel Individual-based Determination of Postoperative Cognitive Dysfunction in Mice

Contact Info

Product

Resources

About