Minocycline upregulates cyclic AMP response element binding protein and brain-derived neurotrophic factor in the hippocampus of&amp;nbsp;cerebral ischemia rats and improves behavioral&amp;nbsp;deficits

Zhang, Yu; Xiao, Ming; He, Wenbo; Cai, Zhiyou

doi:10.2147/ndt.s73836

Cited by 23 publications

(16 citation statements)

References 56 publications

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“…Several findings have shown that the dysregulation of the CREB-BDNF cascade has been involved in cognitive impairment [29]. The neurons of the hippocampus of aged animals showed a down-regulation of BDNF and p-CREB expression, associated with learning and memory impairment [30, 31], which was also similar with our result.…”

Section: Discussionsupporting

confidence: 91%

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

Guo

et al. 2017

Oncotarget

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Ketamine has been reported to impair the capacity for learning and memory. This study examined whether these capacities were also altered in the offspring and investigated the role of the CREB signaling pathway in pregnant rats, subjected to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris water maze task, contextual and cued fear conditioning, and olfactory tasks were executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats were sacrificed on B30. Nerve density and dendritic spine density were examined via Nissl’s and Golgi staining. Simultaneously, the contents of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII), p-CaMKII, CaMKIV, p-CaMKIV, Extracellular Regulated Protein Kinases (ERK), p-ERK, Protein Kinase A (PKA), p-PKA, cAMP-Response Element Binding Protein (CREB), p-CREB, and Brain Derived Neurotrophic Factor (BDNF) were detected in the hippocampus. We pretreated PC12 cells with both PKA inhibitor (H89) and ERK inhibitor (SCH772984), thus detecting levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. The results revealed that ketamine impaired the learning ability and spatial as well as conditioned memory in the offspring, and significantly decreased the protein levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. We found that ERK and PKA (but not CaMKII or CaMKIV) have the ability to regulate the CREB-BDNF pathway during ketamine-induced anesthesia in pregnant rats. Furthermore, ERK and PKA are mutually compensatory for the regulation of the CREB-BDNF pathway.

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Section: Discussionsupporting

confidence: 91%

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

Guo

et al. 2017

Oncotarget

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“…Our findings showed a relationship between obesity-associated cognitive decline and decreases in the density of dendritic spines, primary sites of excitatory synapses, which have been linked to synaptic plasticity and cognitive function (Yuste and Bonhoeffer, 2001;Yuste, 2011). Restoring dendritic spine density in obese mice to control values with minocycline treatment was associated with restored cognitive function.…”

Section: Discussionmentioning

confidence: 54%

“…Because dendritic spines, the primary sites of excitatory synapses, have been linked to synaptic plasticity and cognition (Yuste and Bonhoeffer, 2001; Yuste, 2011), we hypothesized that they might be altered by obesity. Using DiI labeling, we examined dendritic spine density in two neuronal populations of the dorsal hippocampus: the GCs of the DG and the pyramidal cells of the CA1 region.…”

Section: Obesity Is Associated With Decreased Dendritic Spine Densitymentioning

confidence: 99%

Microglia Play an Active Role in Obesity-Associated Cognitive Decline

et al. 2018

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Obesity affects >600 million people worldwide, a staggering number that appears to be on the rise. One of the lesser known consequences of obesity is its deleterious effects on cognition, which have been well documented across many cognitive domains and age groups. To investigate the cellular mechanisms that underlie obesity-associated cognitive decline, we used diet-induced obesity in male mice and found memory impairments along with reductions in dendritic spines, sites of excitatory synapses, increases in the activation of microglia, the brain's resident immune cells, and increases in synaptic profiles within microglia, in the hippocampus, a brain region linked to cognition. We found that partial knockdown of the receptor for fractalkine, a chemokine that can serve as a "find me" cue for microglia, prevented microglial activation and cognitive decline induced by obesity. Furthermore, we found that pharmacological inhibition of microglial activation in obese mice was associated with prevention of both dendritic spine loss and cognitive degradation. Finally, we observed that pharmacological blockade of microglial phagocytosis lessened obesity-associated cognitive decline. These findings suggest that microglia play an active role in obesity-associated cognitive decline by phagocytosis of synapses that are important for optimal function. Obesity in humans correlates with reduced cognitive function. To investigate the cellular mechanisms underlying this, we used diet-induced obesity in mice and found impaired performance on cognitive tests of hippocampal function. These deficits were accompanied by reduced numbers of dendritic spines, increased microglial activation, and increased synaptic profiles within microglia. Inhibition of microglial activation by transgenic and pharmacological methods prevented cognitive decline and dendritic spine loss in obese mice. Moreover, pharmacological inhibition of the phagocytic activity of microglia was also sufficient to prevent cognitive degradation. This work suggests that microglia may be responsible for obesity-associated cognitive decline and dendritic spine loss.

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“…Post-stroke cognitive impairment can range from mild cognitive decline to dementia [ 47 ]. Cerebral ischemia induces free radical formation, glutamate stress, oxidative stress and hypoxic stress, all of which contribute to neuronal injury and cognitive impairments [ 48 ]. Stroke-related dementia is associated with fluctuations in C-reactive protein (CRP), IL-6 and IL-10 in blood serum and cerebrospinal fluid [ 47 ].…”

Section: Stroke-induced Dementia As a Potential Target For Melatonmentioning

confidence: 99%

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

et al. 2020

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Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system. Melatonin-based therapies have been shown to provide neuroprotective effects in the setting of ischemic stroke by mitigating neuroinflammation and accelerating brain tissue restoration. Melatonin treatment includes injection of exogenous melatonin, pineal gland grafting and melatonin-mediated stem cell therapy. This review will discuss the current preclinical and clinical studies investigating melatonin-based therapeutics to treat stroke.

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Minocycline upregulates cyclic AMP response element binding protein and brain-derived neurotrophic factor in the hippocampus of cerebral ischemia rats and improves behavioral deficits

Cited by 23 publications

References 56 publications

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

Microglia Play an Active Role in Obesity-Associated Cognitive Decline

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

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