Reelin Signaling Specifies the Molecular Identity of the Pyramidal Neuron Distal Dendritic Compartment

The mycobiont and whole thallus cultures of Roccella montagnei Bel. were established using soredia as an inoculum.The mycobiont cultures showed optimum growth, biomass and biosynthesis of compounds in Lilly and Barnett medium with glucose as a carbon source, micronutrients and vitamins. After the incubation period of 180 days, the cultures were harvested, and their biomass and secondary compound profiles were analysed. The HPTLC chromatogram of the acetone extract of the NT and mycobiont cultures revealed erythrinas the major biosynthesized compound in both and identified as a key biosynthate by R. montagnei. Further, the NT biosynthesized 5 additional compounds and themycobiont cultures biosynthesized 6 additional compounds. The molecular identity of the cultured mycobiont was confirmed using nuclear ribosomal Internal Transcribed Spacer (ITS) as well as the secondary chemistry. Lichen compound erythrin was identified as a key biosynthate by the cultures.

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Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2/NF-κB Pathway in Transgenic Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms22126603 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6603

Author(s):

Bushra Shal ◽

Adnan Khan ◽

Ashraf Ullah Khan ◽

Rahim Ullah ◽

Gowhar Ali ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Neuroprotective Effect ◽

Annexin V ◽

Memory Deficit ◽

Y Maze ◽

Spatial Memory Deficit ◽

Aβ Aggregation ◽

Ft Ir ◽

Reelin Signaling

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H2O2-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1–42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.

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Suppression of pyramidal neuron G protein-gated inwardly rectifying K+ channel signaling impairs prelimbic cortical function and underlies stress-induced deficits in cognitive flexibility in male, but not female, mice

Neuropsychopharmacology ◽

10.1038/s41386-021-01063-w ◽

2021 ◽

Author(s):

Eden M. Anderson ◽

Steven Loke ◽

Benjamin Wrucke ◽

Annabel Engelhardt ◽

Skyler Demis ◽

...

Keyword(s):

G Protein ◽

Cognitive Flexibility ◽

Pyramidal Neuron ◽

K Channel ◽

Cortical Function ◽

Female Mice ◽

Inwardly Rectifying

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Maternal Ethanol Exposure Acutely Elevates Src Family Kinase Activity in the Fetal Cortex

Molecular Neurobiology ◽

10.1007/s12035-021-02467-x ◽

2021 ◽

Author(s):

Dandan Wang ◽

Brian W. Howell ◽

Eric C. Olson

Keyword(s):

Tyrosine Phosphorylation ◽

Cortical Neurons ◽

Molecular Mechanisms ◽

Fetal Brain ◽

Ethanol Exposure ◽

Src Family Kinase ◽

Cortical Cells ◽

Signaling Systems ◽

Sustained Reduction ◽

Reelin Signaling

AbstractFetal alcohol syndrome (FAS) is characterized by disrupted fetal brain development and postnatal cognitive impairment. The targets of alcohol are diverse, and it is not clear whether there are common underlying molecular mechanisms producing these disruptions. Prior work established that acute ethanol exposure causes a transient increase in tyrosine phosphorylation of multiple proteins in cultured embryonic cortical cells. In this study, we show that a similar tyrosine phosphorylation transient occurs in the fetal brain after maternal dosing with ethanol. Using phospho-specific antibodies and immunohistochemistry, we mapped regions of highest tyrosine phosphorylation in the fetal cerebral cortex and found that areas of dendritic and axonal growth showed elevated tyrosine phosphorylation 10 min after maternal ethanol exposure. These were also areas of Src expression and Src family kinase (SFK) activation loop phosphorylation (pY416) expression. Importantly, maternal pretreatment with the SFK inhibitor dasatinib completely prevents both the pY416 increase and the tyrosine phosphorylation response. The phosphorylation response was observed in the perisomatic region and neurites of immature migrating and differentiating primary neurons. Importantly, the initial phosphotyrosine transient (~ 30 min) targets both Src and Dab1, two critical elements in Reelin signaling, a pathway required for normal cortical development. This initial phosphorylation response is followed by sustained reduction in Ser3 phosphorylation of n-cofilin, a critical actin severing protein and an identified downstream effector of Reelin signaling. This biochemical disruption is associated with sustained reduction of F-actin content and disrupted Golgi apparatus morphology in developing cortical neurons. The finding outlines a model in which the initial activation of SFKs by ethanol has the potential to disrupt multiple developmentally important signaling systems for several hours after maternal exposure.

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