Water-Soluble Arginyl–Diosgenin Analog Attenuates Hippocampal Neurogenesis Impairment Through Blocking Microglial Activation Underlying NF-κB and JNK MAPK Signaling in Adult Mice Challenged by LPS

2019 ◽  
Vol 56 (9) ◽  
pp. 6218-6238 ◽  
Author(s):  
Bangrong Cai ◽  
Kyung-Joo Seong ◽  
Sun-Woong Bae ◽  
Min Suk Kook ◽  
Changju Chun ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Mapk Signaling ◽  
Hippocampal Neurogenesis ◽  
Water Soluble ◽  
Adult Mice

scholarly journals GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurogenesis ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
In Vitro Experiments ◽  
Adult Mice

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

scholarly journals Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain

2020 ◽  
Vol 117 (41) ◽  
pp. 25818-25829
Author(s):  
Xinxing Wang ◽  
Hanxiao Liu ◽  
Johannes Morstein ◽  
Alexander J. E. Novak ◽  
Dirk Trauner ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Energy Homeostasis ◽  
Inhibitory Neuron ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Neuron Activity ◽  
Adult Mice ◽  
Sphingosine 1 Phosphate ◽  
Underlying Mechanisms

Hippocampus-engaged behaviors stimulate neurogenesis in the adult dentate gyrus by largely unknown means. To explore the underlying mechanisms, we used tetrode recording to analyze neuronal activity in the dentate gyrus of freely moving adult mice during hippocampus-engaged contextual exploration. We found that exploration induced an overall sustained increase in inhibitory neuron activity that was concomitant with decreased excitatory neuron activity. A mathematical model based on energy homeostasis in the dentate gyrus showed that enhanced inhibition and decreased excitation resulted in a similar increase in neurogenesis to that observed experimentally. To mechanistically investigate this sustained inhibitory regulation, we performed metabolomic and lipidomic profiling of the hippocampus during exploration. We found sustainably increased signaling of sphingosine-1-phosphate, a bioactive metabolite, during exploration. Furthermore, we found that sphingosine-1-phosphate signaling through its receptor 2 increased interneuron activity and thus mediated exploration-induced neurogenesis. Taken together, our findings point to a behavior-metabolism circuit pathway through which experience regulates adult hippocampal neurogenesis.

scholarly journals N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 516 ◽  
Author(s):  
Anna A. Tyrtyshnaia ◽  
Evgenia L. Egorova ◽  
Anna A. Starinets ◽  
Arina I. Ponomarenko ◽  
Ekaterina V. Ermolenko ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Microglial Activation ◽  
Lipid Analysis ◽  
Hippocampal Neurogenesis ◽  
Raw Material ◽  
Long Term Memory ◽  
Inflammatory Factor ◽  
Behavioral Experiments ◽  
Chronic Neuropathic Pain ◽  
The Brain

Chronic neuropathic pain is a condition that causes both sensory disturbances and a variety of functional disorders, indicating the involvement of various brain structures in pain pathogenesis. One of the factors underlying chronic neuropathic pain is neuroinflammation, which is accompanied by microglial activation and pro-inflammatory factor release. N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endocannabinoid-like metabolite synthesized endogenously from docosahexaenoic acid. Synaptamide exhibits anti-inflammatory activity and improves neurite outgrowth, neurogenesis, and synaptogenesis within the hippocampus. This study aims to evaluate the effects of synaptamide obtained by the chemical modification of DHA, extracted from the Far Eastern raw material Berryteuthis magister on neuroinflammatory response and hippocampal neurogenesis changes during neuropathic pain. The study of microglial protein and cytokine concentrations was performed using immunohistochemistry and ELISA. The brain lipid analysis was performed using the liquid chromatography-mass spectrometry technique. Behavioral experiments showed that synaptamide prevented neuropathic pain-associated sensory and behavioral changes, such as thermal allodynia, impaired locomotor activity, working and long-term memory, and increased anxiety. Synaptamide attenuated microglial activation, release of proinflammatory cytokines, and decrease in hippocampal neurogenesis. Lipid analysis revealed changes in the brain N-acylethanolamines composition and plasmalogen concentration after synaptamide administration. In conclusion, we show here that synaptamide may have potential for use in preventing or treating neuropathic cognitive pain and emotional effects.

Toluene inhibits hippocampal neurogenesis in adult mice

2010 ◽  
Vol 94 (4) ◽  
pp. 588-594 ◽  
Author(s):  
Heung-Sik Seo ◽  
Miyoung Yang ◽  
Myoung-Sub Song ◽  
Joong-Sun Kim ◽  
Sung-Ho Kim ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Mice

scholarly journals Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice

2015 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuan Yang ◽  
Meikui Zhang ◽  
Xiaoni Kang ◽  
Chen Jiang ◽  
Huan Zhang ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Microglial Activation ◽  
Hippocampal Neurogenesis ◽  
Memory Ability

scholarly journals Distinct Effects of Chronic Dopaminergic Stimulation on Hippocampal Neurogenesis and Striatal Doublecortin Expression in Adult Mice

2016 ◽  
Vol 10 ◽  
Author(s):  
Rachele Salvi ◽  
Tobias Steigleder ◽  
Johannes C. M. Schlachetzki ◽  
Elisabeth Waldmann ◽  
Stefan Schwab ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Mice ◽  
Dopaminergic Stimulation

scholarly journals Ghrelin Regulates Hippocampal Neurogenesis in Adult Mice

2009 ◽  
Vol 56 (3) ◽  
pp. 525-531 ◽  
Author(s):  
Minho MOON ◽  
Sehee KIM ◽  
Lakkyong HWANG ◽  
Seungjoon PARK
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Mice

scholarly journals Suppressor of fused controls perinatal expansion and quiescence of future dentate adult neural stem cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Hirofumi Noguchi ◽  
Jesse Garcia Castillo ◽  
Kinichi Nakashima ◽  
Samuel J Pleasure
Keyword(s):  
Stem Cells ◽  
Sonic Hedgehog ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Quiescent State ◽  
Shh Signaling ◽  
Suppressor Of Fused ◽  
Adult Mice ◽  
Adult Nscs ◽  
Signaling Activity

Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. However, establishment and maintenance of quiescent NSC pools during development is not understood. Here, we show that Suppressor of Fused (Sufu) controls establishment of the quiescent NSC pool during mouse dentate gyrus (DG) development by regulating Sonic Hedgehog (Shh) signaling activity. Deletion of Sufu in NSCs early in DG development decreases Shh signaling activity leading to reduced proliferation of NSCs, resulting in a small quiescent NSC pool in adult mice. We found that putative adult NSCs proliferate and increase their numbers in the first postnatal week and subsequently enter a quiescent state towards the end of the first postnatal week. In the absence of Sufu, postnatal expansion of NSCs is compromised, and NSCs prematurely become quiescent. Thus, Sufu is required for Shh signaling activity ensuring expansion and proper transition of NSC pools to quiescent states during DG development.

scholarly journals Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9545
Author(s):  
Rubén Darío Castro-Torres ◽  
Jordi Olloquequi ◽  
Miren Etchetto ◽  
Pablo Caruana ◽  
Luke Steele ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hippocampal Neurons ◽  
Gene Deletion ◽  
Granule Cells ◽  
Hippocampal Neurogenesis ◽  
Mitogen Activated Protein Kinase ◽  
Jnk Pathway ◽  
Adult Mice ◽  
Mitogen Activated Protein ◽  
Genetic Deletion

(1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of Mkk4 and Mkk7 (upstream activators of JNK) in adult mice is not reported. The aim of this study was to induce the genetic deletion of Mkk4/Mkk7 in adult mice and analyze their effect in hippocampal neurogenesis. (2) Methods: To achieve this goal, Actin-CreERT2 (Cre+/−), Mkk4flox/flox, Mkk7flox/flox mice were created. The administration of tamoxifen in these 2-month-old mice induced the gene deletion (Actin-CreERT2 (Cre+/−), Mkk4∆/∆, Mkk7∆/∆ genotype), which was verified by PCR, Western blot, and immunohistochemistry techniques. (3) Results: The levels of MKK4/MKK7 at 7 and 14 days after tamoxifen administration were not eliminated totally in CNS, unlike what happens in the liver and heart. These data could be correlated with the high levels of these proteins in CNS. In the hippocampus, the deletion of Mkk4/Mkk7 induced a misalignment position of immature hippocampal neurons together with alterations in their dendritic architecture pattern and maturation process jointly to the diminution of JNK phosphorylation. (4) Conclusion: All these data supported that the MKK4/MKK7–JNK pathway has a role in adult neurogenic activity.

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