Synaptogenesis

Body size varies across 21 orders of magnitudes in the animal kingdom [1]. In contrast to most organs, which scale through the proliferation of dividing cells of similar size, brains expand by modulating the size of non-dividing neuronal cells to innervate space during development [2]. Consequently, there is a notable variation in neuronal size and structure within individual brains and across species [3]. Considering that size inherently affects the rates of biological structures and processes, from cellular metabolism to information processing [4], the ability of neurons to maintain essentia

…axis modulates dendrite elongation and synaptogenesis. However, whether Cdh1 plays a role in stroke remain

…by promoting neurite outgrowth and synaptogenesis. This study used a weight-drop model to induce mild brain trauma in both C57BL/6 (wildtype, WT) and CCL5 knockout (CCL5-KO) mice. The recovery of motor and sensory neurological functions, and synapse structure and proteins were impaired in CCL5-KO

Cypin (cytosolic PSD-95 interactor) is the most highly expressed guanine deaminase in the brain. Cypin regulates neuronal development by increasing dendritogenesis, modifying dendritic spine morphology, and protecting neurons from injury. To identify binding partners to cypin that may act to mediate these functions, we performed a yeast two-hybrid screen of a rat brain cDNA library with cypin as bait. One of the interactors identified is the beta 7 subunit of the proteasome. Using ubiquitin-independent and ubiquitin-dependent sensors in cultured cells, we found that cypin acts via both pathway

Cannabis use during pregnancy is associated with alterations in the neurodevelopment of exposed children, including difficulties in school learning. Although inhalation is the main route of consumption in humans, there are few reports that have attempted to replicate this route for the preclinical study of prenatal exposure. The aim of this study is to analyze the impact of chronic prenatal exposure to vaporized cannabis on the development and functionality of the hippocampus of offspring. Pregnant rats were daily exposed to chronic cannabis vaporization or air vaporization (control group) fro

Cognitive impairment and disturbed excitatory-inhibitory balance in the brain have been linked to severe psychiatric illnesses such as schizophrenia, affective disorders, and autism spectrum disorders. Erythropoietin (EPO) may have a role in mitigating them by rectifying hippocampal transcriptional networks and synaptic architectures of pyramidal lineages when administered to juvenile mice. How EPO involves interneurons to rebuild synapses is an impending puzzle. After examining ~12,000 single-nuclei transcriptomic data, we generated a comprehensive molecular atlas of hippocampal interneurons,

…impact on postnatal neurogenesis and synaptogenesis remains elusive. Thus, the main goal of this work was to dissect caffeine effects on the differentiation and maturation of postnatal NSCs into neurons.Our results indicate

The DPYSL5 (Dihydropyrimidinase like 5) gene encodes a cytosolic protein which regulates axonal guidance and neuritic growth. We initially described two missense mutations (p.Glu41Lys, recurrent ; p.Gly47Arg) in DPYSL5 gene in nine individuals presenting intellectual disability and agenesis of the corpus callosum. Interestingly, both variants caused abnormal neuronal development and impaired interaction between DPYSL5 and MAP2 and TUBB3 proteins. Recently, a third de novo variant (p.Glu25Lys) was identified in four individuals with a similar clinical phenotype. Various studies described DPYSL5

…early brain development and later synaptogenesis by genetic and environmental factors. Multiple proteins have been shown to participate in the initiation and func

Alternative splicing is a crucial mechanism expanding transcriptome and proteome diversity, with post-translational modifications further enhancing this complexity. Our research focuses on Neurofibromatosis-1 (NF-1), caused by mutations in the NF1 gene that encodes neurofibromin and impacts both learning as well as glioblastoma development. Major alternate exons in the NF1 mRNA are exon31, involved in the production of transcripts and isoforms with different RasGAP potencies; and exon51, which bears a nuclear localization signal (NLS) leading to the production of NLS variants that enter the nu

…effects in the hippocampus, promoting synaptogenesis and synaptic plasticity. Meanwhile, rodents with altered leptin signaling exhibit impairments in these processes and defects in hippocampal-related functions. Leptin increases mushroom spines and the frequency of mini excitatory postsynaptic currents (mEPSCs) in developing hippocampal neurons, evidencing increased functional glutamatergic synapses. Given the presu

…that HOXA5 may act as a regulator of synaptogenesis, a process involving synapse establishment and maturation. Interestingly, the early postnatal period corresponds to the window during which the precerebellar circuitry goes through synaptogenesis.In th

Purkinje cells (PCs) are known to express both GluK1 and GluK4 kainate receptor (KAR) subunits, but the exact role of KARs in synaptic information transfer to PCs is unknown. In this study, we discovered that climbing fiber (CF) to PC synapses contain heteromeric GluK1/GluK4 synaptic KARs. Genetic deletion of Grik4, which encodes for GluK4 subunits, resulted in the lack of synaptic but not extrasynaptic KARs, while deletion of Grik1 (GluK1 subunits) eliminated both synaptic and extrasynaptic KARs. Surprisingly, the absence of synaptic KARs led to a significant reduction in the EPSC component m

In humans with alcohol use disorders (AUD), stress often triggers craving and relapse to alcohol drinking. This characteristic can be modeled in laboratory using stress-induced reinstatement. Here, we showed that in both male and female rats, an increased sensitivity to develop stress-induced reinstatement is promoted by decreased expression of Prdm2, a gene that encodes histone methyltransferase, due to alcohol-induced DNA hypermethylation in the dorsomedial prefrontal cortex (dmPFC). Consistent with our preclinical data, we found that humans with AUD had lowered PRDM2 expression in the prefr

Opioids use cause thousands of deaths per year in United States. Lately, several studies have been focused on ibogaine (IBO), a psychoactive alkaloid with the ability to treat drug dependence and reduce withdrawal syndrome. The mechanism by which IBO exerts its anti-addictive effects is unknown. This study aims to identify changes in the gene expression after a single oral dose of IBO in different brain areas. Male and female C57BL/6 mice were treated with 60 mg/kg of IBO by gavage. Four hours post-administration frontal cortex samples of three males and three females were obtained to perform

…receptors and hormones influence synaptogenesis. The development of glutamatergi

GABAergic interneurons are chiefly responsible for controlling the activity of local circuits in the cortex. Chandelier cells (ChCs) are a type of GABAergic interneuron that control the output of hundreds of neighbouring pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS). Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. We have investigated the emergence and plasticity of axo-axonic synapses in layer 2/3 of the somatosensory cortex (S1) and found that ChCs follow w

Pediatric high-grade gliomas (pHGG) are a devastating group of diseases that urgently require novel therapeutic options. We have previously demonstrated that pHGGs directly synapse onto neurons and the subsequent tumor cell depolarization, mediated by calcium-permeable AMPA channels, promotes their proliferation. The regulatory mechanisms governing these postsynaptic connections are unknown. Here, we investigated the role of BDNF-TrkB signaling in modulating the plasticity of the malignant synapse. BDNF ligand activation of its canonical receptor, TrkB (which is encoded for by the gene NTRK2),

Early experiments studying the effects of lesions of the Hippocampus have reported that recent memories are often unavailable to be retrieved, while old memories are successfully reminded. These observations have led to state the theory of Systems Consolidation. This is the process by which the fast-learning Hippocampus replays the encoded memory during sleep and thus consolidates the corresponding memory in the Neocortex [1]. Formation of memory would take longer in the Neocortex because of its much larger spatial scale compared to the Hippocampus, and thus requires axonal growth and synaptog

…migration, differentiation, synaptogenesis, and synaptic pruning. Perturbations to any of these processes, for example associated with ion channel gene mutations (i.e., channelopathies), can underlie neurodevelopmental disorders such as neonatal and infantile epilepsies, strongly impair psychomotor development and cause persistent deficits in cognition, motor skills, or motor control. The therapeutic options available are very limited, and prophylactic therapies for patients at an increas