Early construction of the thalamocortical axon pathway requires JNK signaling within the ventral forebrain

Thalamocortical connectivity is essential for normal brain function. This important pathway is established during development, when thalamic axons extend a long distance through the forebrain before reaching the cerebral cortex. In this study, we identify a novel role for the c-Jun N-terminal Kinase (JNK) signaling pathway in guiding thalamocortical axons through intermediate target territories. Complete genetic removal of JNK signaling from the Distal-less 5/6 (Dlx5/6) domain in mice prevents thalamocortical axons from crossing the diencephalon-telencephalon boundary (DTB) and the internal capsule fails to form. Ventral telencephalic cells critical for thalamocortical axon extension including corridor and guidepost neurons are also disrupted. In addition, corticothalamic, striatonigral, and nigrostriatal axons fail to cross the DTB. Analyses of different JNK mutants demonstrates that thalamocortical axon pathfinding has a non-autonomous requirement for JNK signaling. We conclude that JNK signaling within the Dlx5/6 territory enables the construction of major axonal pathways in the developing forebrain.

Download Full-text

Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.690475 ◽

2021 ◽

Vol 15 ◽

Author(s):

Emilia Asante ◽

Devynn Hummel ◽

Suman Gurung ◽

Yasmin M. Kassim ◽

Noor Al-Shakarji ◽

...

Keyword(s):

Neuromuscular Junctions ◽

Larval Feeding ◽

Normal Brain ◽

Axon Pathfinding ◽

Loss Of Function ◽

Jaw Muscles ◽

Normal Brain Function ◽

Functional Consequences ◽

And Migration ◽

Circuit Function

Precise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit function, we studied a zebrafish frizzled3a (fzd3a) loss-of-function mutant off-limits (olt) where the facial branchiomotor (FBM) neurons fail to migrate out of their birthplace. A jaw movement assay, which measures the opening of the zebrafish jaw (gape), showed that the frequency of gape events, but not their amplitude, was decreased in olt mutants. Consistent with this, a larval feeding assay revealed decreased food intake in olt mutants, indicating that the FBM circuit in mutants generates defective functional outputs. We tested various mechanisms that could generate defective functional outputs in mutants. While fzd3a is ubiquitously expressed in neural and non-neural tissues, jaw cartilage and muscle developed normally in olt mutants, and muscle function also appeared to be unaffected. Although FBM neurons were mispositioned in olt mutants, axon pathfinding to jaw muscles was unaffected. Moreover, neuromuscular junctions established by FBM neurons on jaw muscles were similar between wildtype siblings and olt mutants. Interestingly, motor axons innervating the interhyoideus jaw muscle were frequently defasciculated in olt mutants. Furthermore, GCaMP imaging revealed that mutant FBM neurons were less active than their wildtype counterparts. These data show that aberrant positioning of FBM neurons in olt mutants is correlated with subtle defects in fasciculation and neuronal activity, potentially generating defective functional outputs.

Download Full-text

Connecting the Neurobiology of Developmental Brain Injury: Neuronal Arborisation as a Regulator of Dysfunction and Potential Therapeutic Target

International Journal of Molecular Sciences ◽

10.3390/ijms22158220 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8220

Author(s):

Ane Goikolea-Vives ◽

Helen B. Stolp

Keyword(s):

Neurodevelopmental Disorders ◽

Synapse Formation ◽

Neurodevelopmental Disorder ◽

Therapeutic Benefit ◽

Normal Brain ◽

Environmental Pressures ◽

Axon Extension ◽

Neurodevelopmental Disease ◽

Normal Brain Function ◽

Pharmacological Modification

Neurodevelopmental disorders can derive from a complex combination of genetic variation and environmental pressures on key developmental processes. Despite this complex aetiology, and the equally complex array of syndromes and conditions diagnosed under the heading of neurodevelopmental disorder, there are parallels in the neuropathology of these conditions that suggest overlapping mechanisms of cellular injury and dysfunction. Neuronal arborisation is a process of dendrite and axon extension that is essential for the connectivity between neurons that underlies normal brain function. Disrupted arborisation and synapse formation are commonly reported in neurodevelopmental disorders. Here, we summarise the evidence for disrupted neuronal arborisation in these conditions, focusing primarily on the cortex and hippocampus. In addition, we explore the developmentally specific mechanisms by which neuronal arborisation is regulated. Finally, we discuss key regulators of neuronal arborisation that could link to neurodevelopmental disease and the potential for pharmacological modification of arborisation and the formation of synaptic connections that may provide therapeutic benefit in the future.

Download Full-text

A Survey on Detection and Classification of Brain Tumor Using Image Processing Techniques

International Journal of Scientific Research in Computer Science Engineering and Information Technology ◽

10.32628/cseit2063211 ◽

2020 ◽

pp. 967-973

Author(s):

V. Deepika ◽

T. Rajasenbagam

Keyword(s):

Image Processing ◽

Brain Tumor ◽

Soft Tissues ◽

Tumor Detection ◽

Tumor Classification ◽

Normal Brain ◽

Image Processing Techniques ◽

Normal Brain Function ◽

Processing Techniques ◽

The Brain

A brain tumor is an uncontrolled growth of abnormal brain tissue that can interfere with normal brain function. Although various methods have been developed for brain tumor classification, tumor detection and multiclass classification remain challenging due to the complex characteristics of the brain tumor. Brain tumor detection and classification are one of the most challenging and time-consuming tasks in the processing of medical images. MRI (Magnetic Resonance Imaging) is a visual imaging technique, which provides a information about the soft tissues of the human body, which helps identify the brain tumor. Proper diagnosis can prevent a patient's health to some extent. This paper presents a review of various detection and classification methods for brain tumor classification using image processing techniques.

Download Full-text

Regulation of the JNK signaling pathway by dual leucine zipper kinase DLK

Hereditas (Beijing) ◽

10.3724/sp.j.1005.2010.00785 ◽

2010 ◽

Vol 32 (8) ◽

pp. 785-790 ◽

Cited By ~ 1

Author(s):

Xian-Jue MA ◽

Lei XUE

Keyword(s):

Signaling Pathway ◽

Leucine Zipper ◽

Jnk Signaling ◽

Jnk Signaling Pathway

Download Full-text

MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap

Oncogene ◽

10.1038/sj.onc.1207817 ◽

2004 ◽

Vol 23 (36) ◽

pp. 6023-6030 ◽

Cited By ~ 45

Author(s):

Ryoji Yao ◽

Yasuko Natsume ◽

Tetsuo Noda

Keyword(s):

Signaling Pathway ◽

Scaffold Protein ◽

Jnk Signaling ◽

Jnk Signaling Pathway

Download Full-text

The role of GABAA receptor biogenesis, structure and function in epilepsy

Biochemical Society Transactions ◽

10.1042/bst0340863 ◽

2006 ◽

Vol 34 (5) ◽

pp. 863-867 ◽

Cited By ~ 14

Author(s):

S. Mizielinska ◽

S. Greenwood ◽

C.N. Connolly

Keyword(s):

Gabaa Receptor ◽

Structure And Function ◽

Inhibitory Synapses ◽

Normal Brain ◽

Synaptic Targeting ◽

Acid Type ◽

Normal Brain Function ◽

And Function ◽

The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

Download Full-text

Impacts of Iron Metabolism Dysregulation on Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201250 ◽

2021 ◽

Vol 80 (4) ◽

pp. 1439-1450

Author(s):

Najla Jouini ◽

Zakaria Saied ◽

Samia Ben Sassi ◽

Fatma Nebli ◽

Taieb Messaoud ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Antioxidant System ◽

Plasma Concentrations ◽

Normal Brain ◽

Cognitively Normal ◽

Iron Trafficking ◽

Major Species ◽

Normal Brain Function ◽

Calcium Magnesium

Background: Iron plays an important role in maintaining cell survival, with normal iron trafficking known to be regulated by the ceruloplasmin-transferrin (Cp-Tf) antioxidant system. Disruption to this system is thought to be detrimental to normal brain function. Objective: To determine whether an imbalance of iron and the proteins involved in its metabolism (ceruloplasmin and transferrin) are linked to Alzheimer’s disease (AD) and to the expression of amyloid-beta (Aβ) peptide 1–42 (Aβ1–42), which is a major species of Aβ, and the most toxic. Methods: We evaluated the concentrations of iron, calcium, magnesium, and Aβ1–42 in the cerebrospinal fluid (CSF) of patients with AD and cognitively normal controls. Correlations between the components of the Cp-Tf antioxidant system in plasma were studied to determine the role of peripheral blood in the onset and/or development of AD. We used commercial ELISA immunoassays to measure Aβ1–42, immunoturbidimetry to quantify ceruloplasmin and transferrin, and colorimetry to quantify iron, calcium, and magnesium. Results: We found that the AD group had lower CSF concentrations of Aβ1–42 (p < 0.001) and calcium (p < 0.001), but a higher CSF concentration of iron (p < 0.001). Significantly lower plasma concentrations of ceruloplasmin (p = 0.003), transferrin (mean, p < 0.001), and iron (p < 0.001) were observed in the AD group than in cognitively normal adults. Moreover, we found a strong interdependence between most of these components. Conclusion: Iron dyshomeostasis has a crucial role in the onset of AD and/or its development. Correcting metal misdistribution is an appealing therapeutic strategy for AD.

Download Full-text