dendrite arborization

BACKGROUND: C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons. However, its function is still not clear. We established C1ql3-deficient rats to investigate the role of C1QL3 in the brain. METHODS: C1ql3 knockout (KO) rats were generated using CRISPR/Cas9. C1ql3 KO was determined by polymerase chain reaction (PCR), DNA sequencing, and western blotting. Microglia morphology and cytokine expression with or without lipopolysaccharide (LPS) stimulus were analyzed using immunohistochemistry and real-time PCR...

In mammals, retinal direction selectivity originates from GABAergic/cholinergic amacrine cells (ACs) specifically expressing the sox2 gene. However, the cellular diversity of GABAergic/cholinergic ACs of other vertebrate species remains largely unexplored. Here, we identified 2 morphologically and genetically distinct GABAergic/cholinergic AC types in zebrafish, a previously undescribed bhlhe22+ type and a mammalian counterpart sox2+ type. Notably, while sole sox2 disruption removed sox2+ type, the codisruption of bhlhe22 and bhlhe23 was required to remove bhlhe22+ type...

Brain-derived neurotrophic factor (Bdnf) plays a critical role in brain development, dendritic growth, synaptic plasticity, as well as learning and memory. The rodent Bdnf gene contains nine 5' non-coding exons (I-IXa), which are spliced to a common 3' coding exon (IX). Transcription of individual Bdnf variants, which all encode the same BDNF protein, is initiated at unique promoters upstream of each non-coding exon, enabling precise spatiotemporal and activity-dependent regulation of Bdnf expression. Although prior evidence suggests that Bdnf transcripts containing exon I (Bdnf I) or exon IV (Bdnf IV) are uniquely regulated by neuronal activity, the functional significance of different Bdnf transcript variants remains unclear...

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of pathological structures, but they have produced many contradictory findings. Since correctly identifying the underlying neuroanatomical changes is critical to advancing TBI research, we compared three commonly used markers for their ability to detect TBI pathological structures: Fluoro-Jade C, the rabbit monoclonal antibody Y188 against amyloid precursor protein and the NeuroSilver kit were used to stain adjacent slices from naïve or injured mouse brains harvested at different time points from 30 min to 3 months after lateral fluid percussion injury...

Cancer-related cognitive impairments (CRCI) are neurological complications associated with cancer treatment, and greatly affect cancer survivors' quality of life. Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis, learning and memory. The reduction of BDNF is associated with the decrease in cognitive function in various neurological disorders. Few pre-clinical studies have reported on the effects of chemotherapy and medical stress on BDNF levels and cognition. The present study aimed to compare the effects of medical stress and cisplatin on serum BDNF levels and cognitive function in 9-month-old female Sprague Dawley rats to age-matched controls...

Melanin-concentrating hormone (MCH) cells in the hypothalamus regulate fundamental physiological functions like energy balance, sleep, and reproduction. This diversity may be ascribed to the neurochemical heterogeneity among MCH cells. One prominent subpopulation of MCH cells coexpresses cocaine- and amphetamine-regulated transcript (CART), and as MCH and CART can have opposing actions, MCH/CART+ and MCH/CART- cells may differentially modulate behavioral outcomes. However, it is not known if there are differences in the cellular properties underlying their functional differences; thus, we compared the neuroanatomical, electrophysiological, and morphological properties of MCH cells in male and female Mch-cre;L10-Egfp reporter mice...

The Pcdhg gene cluster encodes 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules that critically regulate multiple aspects of neural development, including neuronal survival, dendritic and axonal arborization, and synapse formation and maturation. Each γ-Pcdh isoform has unique protein domains-a homophilically-interacting extracellular domain and a juxtamembrane cytoplasmic domain- as well as a C-terminal cytoplasmic domain shared by all isoforms. The extent to which isoform-specific vs...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic basis. ASDs are commonly characterized by impairments in language, restrictive and repetitive behaviors, and deficits in social interactions. Although ASD is a highly heterogeneous disease with many different genes implicated in its etiology, many ASD-associated genes converge on common cellular defects, such as aberrant neuronal morphology and synapse dysregulation. Our previous work revealed that, in mice, complete loss of the ASD-associated X-linked gene NEXMIF results in a reduction in dendritic complexity, a decrease in spine and synapse density, altered synaptic transmission, and ASD-like behaviors...

Hippocampal pyramidal cells possess elaborate dendritic arbors with distinct domains that are targeted with input-specific synaptic sites. This synaptic arrangement is facilitated by synaptic cell-adhesion molecules that act as recognition elements to connect presynaptic and postsynaptic neurons. In this study, we investigate the organization of the synaptic recognition molecule latrophilin-2 at the surface of pyramidal neurons classified by spatial positioning and action potential firing patterns. Surveying two hippocampal neurons that highly express latrophilin-2, late-bursting CA1 pyramidal cells and early-bursting subiculum pyramidal cells, we found the molecule to be differentially positioned on their respective dendritic compartments...

Oxytocin (OXT) plays important roles in autonomic control and behavioral modulation. However, it is unknown how the projection patterns of OXT neurons align with underlying physiological functions. Here, we present the reconstructed single-neuron, whole-brain projectomes of 264 OXT neurons of the mouse paraventricular hypothalamic nucleus (PVH) at submicron resolution. These neurons hierarchically clustered into two groups, with distinct morphological and transcriptional characteristics and mutually exclusive projection patterns...

Adaptor protein complex 4 (AP-4) is a heterotetrameric complex that promotes export of selected cargo proteins from the trans-Golgi network. Mutations in each of the AP-4 subunits cause a complicated form of Hereditary Spastic Paraplegia (HSP). Herein, we report that ApoER2, a receptor in the Reelin signaling pathway, is a cargo of the AP-4 complex. We identify the motif ISSF/Y within the ApoER2 cytosolic domain as necessary for interaction with the canonical signal-binding pocket of the µ4 (AP4M1) subunit of AP-4...

UNLABELLED: Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with non-canonical receptors and unidentified co-receptors; however, the effects of which are less understood. Using high-throughput tandem mass tag LC-MS/MS-based proteomics and gene set enrichment analysis, we identified both shared and unique intracellular pathways activated by Reelin through its canonical and non-canonical signaling in primary murine neurons during dendritic growth and arborization...

Neuronal maturation is the phase during which neurons acquire their final characteristics in terms of morphology, electrical activity, and metabolism. However, little is known about the metabolic pathways governing neuronal maturation. Here, we investigate the contribution of the main metabolic pathways, namely glucose, glutamine, and fatty acid oxidation, during the maturation of primary rat hippocampal neurons. Blunting glucose oxidation through the genetic and chemical inhibition of the mitochondrial pyruvate transporter reveals that this protein is critical for the production of glutamate, which is required for neuronal arborization, proper dendritic elongation, and spine formation...

The precise development of neuronal morphologies is crucial to the establishment of synaptic circuits and, ultimately, proper brain function. Signaling by the axon guidance cue semaphorin 3A (Sema3A) and its receptor complex of neuropilin-1 and plexin-A4 has multifunctional outcomes in neuronal morphogenesis. Downstream activation of the RhoGEF FARP2 through interaction with the lysine-arginine-lysine motif of plexin-A4 and consequent activation of the small GTPase Rac1 promotes dendrite arborization, but this pathway is dispensable for axon repulsion...

An increasing use of plastics in daily life leads to the accumulation of microplastics (MPs) in the environment, posing a serious threat to the ecosystem, including humans. It has been reported that MPs cause neurotoxicity, but the deleterious effect of polystyrene (PS) MPs on neuronal cytoarchitectural morphology in the prefrontal cortex (PFC) region of mice brain remains to be established. In the present study, Swiss albino male mice were orally exposed to 0.1, 1, and 10 ppm PS-MPs for 28 days. After exposure, we found a significant accumulation of PS-MPs with a decreased number of Nissl bodies in the PFC region of the entire treated group compared to the control...

Dendritogenesis, a process of dendritic arbor development, is essential for the formation of functional neuronal networks, and in mammals, it begins in early life and continues into adulthood. It is a highly dynamic process in which dendritic branches form and regress until mature connectivity is achieved. Thereafter, dendritic branches are considered stable and do not undergo substantial rearrangements, although several exceptions have been described in the literature. After this long period of relative stability, significant changes in dendritic branching occur when the brain begins to age...

Neonatal jaundice is one of the most common disorders in the first 2 wk after birth. Unconjugated bilirubin (UCB) is neurotoxic and can cause neurological dysfunction; however, the underlying mechanisms remain unclear. Neurogenesis, neuronal growth, and synaptogenesis are exuberant in the early postnatal stage. In this study, the impact of UCB on neuritogenesis and synaptogenesis in the early postnatal stage was evaluated both in vitro and in vivo. Primary culture neuronal stem and progenitor cells (NSPCs) were treated with UCB during differentiation, and then the neurite length and synapse puncta were measured...

BACKGROUND: Tripartite motif (TRIM46) is a relatively novel protein that belongs to tripartite motif family. TRIM46 organizes parallel microtubule arrays on the axons, which are important for neuronal polarity and axonal function. TRIM46 is highly expressed in the brain, but its biological function in adults has not yet been determined. RESULTS: Trim46 knockout (KO) rat line was established using CRISPR/cas9. Trim46 KO rats had smaller hippocampus sizes, fewer neuronal dendritic arbors and dendritic spines, and shorter and more distant axon initial segment...

Adaptor protein complex 4 (AP-4) is a heterotetrameric complex that promotes protein export from the trans -Golgi network. Mutations in each of the AP-4 subunits cause a complicated form of Hereditary Spastic Paraplegia (HSP). Herein, we report that ApoER2, a receptor in the Reelin signaling pathway, is a cargo of the AP-4 complex. We identify the motif ISSF/Y within the ApoER2 cytosolic domain as necessary for interaction with the canonical signal-binding pocket of the µ4 (AP4M1) subunit of AP-4. AP4E1 -knock-out (KO) HeLa cells and hippocampal neurons from Ap4e1 -KO mice display increased Golgi localization of ApoER2...

Concerns about inappropriate disposal of waste into unsanitary municipal solid waste landfills around the world have been on the increase, and this poses a public health challenge due to leachate production. The neurotoxic effect of Gwagwalada landfill leachate (GLL) was investigated in male adult Wistar rats. Rats were exposed to a 10% concentration of GLL for 21 days. The control group received tap water for the same period of the experiment. Our results showed that neurobehavior, absolute body and brain weights and brain histomorphology as well as parvalbumin interneurons were severely altered, with consequent astrogliosis and microgliosis after 21 days of administrating GLL...