Neuroscience

TDP-43 proteinopathy is the major pathology in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal dementia (FTD). Mounting evidence implicates loss of normal TDP-43 RNA-processing function as a key pathomechanism. However, the RNA targets of TDP-43 differ by report, and have never been formally collated or compared between models and disease, hampering understanding of TDP-43 function.

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons lay the foundation for human development and reproduction, however, the critical cell populations and the entangled mechanisms underlying the development of human GnRH neurons remain poorly understood. Here, by utilizing our established human pluripotent stem cells-derived GnRH neuron model, we decoded the cellular heterogeneity and differentiation trajectories at the single-cell level.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative disorders displaying substantial overlay, although there are substantial differences at the molecular level. Currently, there is no effective treatment for these diseases. The transcription factor NRF2 has been postulated as a promising therapeutic target as it is capable of modulating key pathogenic events affecting cellular homeostasis. However, there is little experimental evidence on the status of this pathway in both ALS and FTD.

Oxytocin (OXT) and oxytocin receptor (OXTR)-mediated signaling control excitability, firing patterns, and plasticity of hippocampal CA2 pyramidal neurons, which are pivotal in generation of brain oscillations and social memory. Nonetheless, the ionic mechanisms underlying OXTR-induced effects in CA2 neurons are not fully understood.

Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a two-week treatment with an HDAC6 inhibitor, administered 3 days after the last dose of cisplatin.

In myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), several areas of demyelination are detectable in mouse cerebral cortex, where neuroinflammation events are associated with scarce inflammatory infiltrates and blood-brain barrier (BBB) impairment. In this condition, the administration of mesenchymal stem cells (MSCs) controls neuroinflammation, attenuating astrogliosis and promoting the acquisition of stem cell traits by astrocytes.

Oxytocin, secreted by oxytocin neurons in the hypothalamus, is an endogenous neuropeptide involved in modulating multiple sensory information processing pathways, and its roles in the brain have been associated with prosocial, maternal, and feeding-related behaviors. Visual information is necessary for initiating these behaviors, with the retina consisting of the first stage in the visual system mediating external stimulus perception. Oxytocin has been detected in the mammalian retina; however, the expression and possible function of oxytocin receptors (OxtR) in the retina remain unknown.

The AUTS2 gene plays major roles during brain development and is associated with various neuropathologies including autism. Data in non-mammalian species are scarce, and the aim of our study was to provide a comprehensive analysis of auts2 evolution in teleost fish, which are widely used for in vivo functional analysis and biomedical purposes. Comparative genomics in 78 species showed that auts2a and auts2b originate from the teleost-specific whole genome duplication (TGD). auts2a, which is highly similar to human AUTS2, was almost systematically retained following TGD.

Neurons in the superficial dorsal horn that express the gastrin-releasing peptide receptor (GRPR) are strongly implicated in spinal itch pathways. However, a recent study reported that many of these correspond to vertical cells, a population of interneurons that are thought to transmit nociceptive information. In this study, we have used a GRPRCreERT2 mouse line to identify and target cells that possess Grpr mRNA.

Opioid exposure is known to cause transcriptomic changes in the nucleus accumbens (NAc). However, no studies to date have investigated cell type-specific transcriptomic changes associated with volitional opioid taking. Here, we use single nucleus RNA sequencing (snRNAseq) to comprehensively characterize cell type-specific alterations of the NAc transcriptome in rats self-administering morphine. One cohort of male Brown Norway rats was injected with acute morphine (10 mg/kg, i.p.) or saline.