A universal neuronal classification and naming scheme based on the neuronal morphology

Abstract Background After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain. Method Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot. Results Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor. Conclusion We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.

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The Protective Mechanism of SIRT1 in the Regulation of Mitochondrial Biogenesis and Mitochondrial Autophagy in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210132 ◽

2021 ◽

pp. 1-9

Author(s):

Fan Ye ◽

Anshi Wu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mitochondrial Biogenesis ◽

Stress Responses ◽

Histone Deacetylases ◽

Neuronal Morphology ◽

Protective Mechanism ◽

Peroxisome Proliferator ◽

Class Iii ◽

Peroxisome Proliferator Activated Receptor

Silent information-regulated transcription factor 1 (SIRT1) is the most prominent and widely studied member of the sirtuins (a family of mammalian class III histone deacetylases). It is a nuclear protein, and the deacetylation of the peroxisome proliferator-activated receptor coactivator-1 has been extensively implicated in metabolic control and mitochondrial biogenesis and is the basis for studies into its involvement in caloric restriction and its effects on lifespan. The present study discusses the potentially protective mechanism of SIRT1 in the regulation of the mitochondrial biogenesis and autophagy involved in the modulation of Alzheimer’s disease, which may be correlated with the role of SIRT1 in affecting neuronal morphology, learning, and memory during development; regulating metabolism; counteracting stress responses; and maintaining genomic stability. Drugs that activate SIRT1 may offer a promising approach to treating Alzheimer’s disease

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Spaceflight affects neuronal morphology and alters transcellular degradation of neuronal debris in adult Caenorhabditis elegans

iScience ◽

10.1016/j.isci.2021.102105 ◽

2021 ◽

Vol 24 (2) ◽

pp. 102105

Author(s):

Ricardo Laranjeiro ◽

Girish Harinath ◽

Amelia K. Pollard ◽

Christopher J. Gaffney ◽

Colleen S. Deane ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Neuronal Morphology

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2-Cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride alters lipopolysaccharide-induced proinflammatory cytokines and neuronal morphology in mouse fetal brain

Neuropharmacology ◽

10.1016/j.neuropharm.2015.10.035 ◽

2016 ◽

Vol 102 ◽

pp. 32-41 ◽

Cited By ~ 3

Author(s):

Eun-A Kim ◽

Chang Hun Cho ◽

Soo Young Choi ◽

Jee-Yin Ahn ◽

Seung-Ju Yang ◽

...

Keyword(s):

Proinflammatory Cytokines ◽

Fetal Brain ◽

Neuronal Morphology

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Critical Role for Kalirin in Nerve Growth Factor Signaling through TrkA

Molecular and Cellular Biology ◽

10.1128/mcb.25.12.5106-5118.2005 ◽

2005 ◽

Vol 25 (12) ◽

pp. 5106-5118 ◽

Cited By ~ 30

Author(s):

Kausik Chakrabarti ◽

Rong Lin ◽

Noraisha I. Schiller ◽

Yanping Wang ◽

David Koubi ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Pc12 Cells ◽

Critical Role ◽

Neuronal Morphology ◽

Neurotrophin Receptor ◽

General Mechanism ◽

Pleckstrin Homology Domain ◽

Pleckstrin Homology ◽

Nerve Growth

ABSTRACT Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low concentration of NGF. Furthermore, elevated Kalirin expression resulted in catalytic activation of TrkA, as demonstrated by in vitro kinase assays and increased NGF-stimulated cellular activation of Rac, Mek, and CREB. Domain mapping demonstrated that the N-terminal Kalirin pleckstrin homology domain mediates the interaction with TrkA. The effects of Kalirin on TrkA provide a molecular basis for the requirement of Kalirin in process extension from PC12 cells and for previously observed effects on axonal extension and dendritic maintenance. The interaction of TrkA with the pleckstrin homology domain of Kalirin may be one example of a general mechanism whereby receptor/Rho GEF pairings play an important role in receptor tyrosine kinase activation and signal transduction.

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WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1713625114 ◽

2017 ◽

Vol 114 (44) ◽

pp. E9308-E9317 ◽

Cited By ~ 26

Author(s):

Meghna Kannan ◽

Efil Bayam ◽

Christel Wagner ◽

Bruno Rinaldi ◽

Perrine F. Kretz ◽

...

Keyword(s):

Corpus Callosum ◽

Brain Development ◽

Brain Connectivity ◽

Neuronal Morphology ◽

Dependent Manner ◽

Wd40 Repeat ◽

Starting Point ◽

Neuronal Regulation ◽

The Family ◽

Cervical Ganglion

The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker (Atg16l1, Coro1c, Dmxl2, and Herc1), thinner (Kif21b and Wdr89), or absent corpus callosum (Wdr47), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy.

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