[Treatment of multiple sclerosis with glatiramer acetate: a new look].

In recent years, the use of a new dosage (40 mg) of glatiramer acetate (GA), which is administered 3 times weekly has become widespread. In Russia, the drug Timexon (produced by the company BIOCAD) was developed and passed successful clinical trials. The final efficacy analysis included 150 patients treated for 12 months.

[Possibilities of art therapy and color therapy in the rehabilitation of multiple sclerosis].

The Purpose Of The Study: To study the effectiveness of non-drug methods of prevention and rehabilitation of patients with various variants of multiple sclerosis (MS) in outpatient settings.

Material And Methods: In a group of 35 patients with limited mobility with various variants of the course of MS, continuous art therapy was performed (art lectures, work with various art materials - markers, pastels, etc.).

[Epidemiology of neuromyelitis optica spectrum disorder].

Neuromyelitis optica spectrum disorder (NMOSD) is a group of rare and mostly severe autoimmune demyelinating central nervous system disorders which prevalence is 0.7-1 per 100.000 population and incidence is 0.

Pain modulates dopamine neurons via a spinal-parabrachial-mesencephalic circuit.

Pain decreases the activity of many ventral tegmental area (VTA) dopamine (DA) neurons, yet the underlying neural circuitry connecting nociception and the DA system is not understood. Here we show that a subpopulation of lateral parabrachial (LPB) neurons is critical for relaying nociceptive signals from the spinal cord to the substantia nigra pars reticulata (SNR). SNR-projecting LPB neurons are activated by noxious stimuli and silencing them blocks pain responses in two different models of pain.

Neuronal activity recruits the CRTC1/CREB axis to drive transcription-dependent autophagy for maintaining late-phase LTD.

Cellular resources must be reorganized for long-term synaptic plasticity during brain information processing, in which coordinated gene transcription and protein turnover are required. However, the mechanism underlying this process remains elusive. Here, we report that activating N-methyl-d-aspartate receptors (NMDARs) induce transcription-dependent autophagy for synaptic turnover and late-phase long-term synaptic depression (L-LTD), which invokes cytoplasm-to-nucleus signaling mechanisms known to be required for late-phase long-term synaptic potentiation (L-LTP).

GPR151 in nociceptors modulates neuropathic pain via regulating P2X3 function and microglial activation.

Neuropathic pain is a major health problem that affects up to 7-10% of the population worldwide. Currently, neuropathic pain is difficult to treat because of its elusive mechanisms. Here we report that orphan G protein-coupled receptor 151 (GPR151) in nociceptive sensory neurons controls neuropathic pain induced by nerve injury.

A novel 3D-printed multi-driven system for large-scale neurophysiological recordings in multiple brain regions.

Background: Electrical probes have been widely used for recording single-unit spike activity and local field potentials (LFPs) in brain regions. However, setting up an easily-assembled large-scale recording in multiple brain regions for long-term and stable neural activity monitoring is still a hard task.

New Method: We established a novel 3D-printed multi-drive system with high-density (up to 256 channels) tetrodes/grid electrodes that enables us to record cortical and subcortical brain regions in freely behaving animals.

Molecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptor.

The glucagon-like peptide-1 (GLP-1) receptor is a validated drug target for metabolic disorders. Ago-allosteric modulators are capable of acting both as agonists on their own and as efficacy enhancers of orthosteric ligands. However, the molecular details of ago-allosterism remain elusive.

A high-resolution cell atlas of the domestic pig lung and an online platform for exploring lung single-cell data.

The genetically engineered pig is regarded as an optimal source of organ transplantation for humans and an excellent model for human disease research, given its comparable physiology to human beings. A myriad of single-cell RNA sequencing (scRNA-seq) data on humans has been reported, but such data on pigs are scarce. Here, we apply scRNA-seq technology to study the cellular heterogeneity of 3-month-old pig lungs, generating the single-cell atlas of 13,580 cells covering 16 major cell types.

The Mitochondria-to-Cytosol HO Gradient Is Caused by Peroxiredoxin-Dependent Cytosolic Scavenging.

Fluorescent protein-based reporters used to measure intracellular HO were developed to overcome the limitations of small permeable dyes. The two major families of genetically encoded redox reporters are the reduction-oxidation sensitive green fluorescent protein (roGFP)-based proteins fused to peroxiredoxins and HyPer and derivatives. We have used the most sensitive probes of each family, roGFP2-Tpx1.

Single-cell brain atlas of Parkinson's disease mouse model.

Parkinson's disease (PD) is a neurodegenerative disease, leading to the impairment of movement execution. PD pathogenesis has been largely investigated, either limited to bulk transcriptomic levels or at certain cell types, which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types. Here, we report the application of single-nucleus RNA-seq on midbrain, striatum, and cerebellum of the α-syn-A53T mouse, a well-established PD mouse model, and matched controls, generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.

Rationally Designed, Self-Assembling, Multifunctional Hydrogel Depot Repairs Severe Spinal Cord Injury.

Following severe spinal cord injury (SCI), dysregulated neuroinflammation causes neuronal and glial apoptosis, resulting in scar and cystic cavity formation during wound healing and ultimately the formation of an atrophic microenvironment that inhibits nerve regrowth. Because of this complex and dynamic pathophysiology, a systemic solution for scar- and cavity-free wound healing with microenvironment remodeling to promote nerve regrowth has rarely been explored. A one-step solution is proposed through a self-assembling, multifunctional hydrogel depot that punctually releases the anti-inflammatory drug methylprednisolone sodium succinate (MPSS) and growth factors (GFs) locally according to pathophysiology to repair severe SCI.

Sex differences in the neuropathological hallmarks of Alzheimer's disease: focus on cognitively intact elderly individuals.

Aims: Women are more vulnerable to Alzheimer's disease (AD) than men. We investigated (i) whether and at what age the AD hallmarks, that is, β-amyloid (Aβ) and hyperphosphorylated Tau (p-Tau) show sex differences; and (ii) whether such sex differences may occur in cognitively intact elderly individuals.

Methods: We first analysed the entire post-mortem brain collection of all non-demented 'controls' and AD donors from our Brain Bank (245 men and 403 women), for the presence of sex differences in AD hallmarks.

Structural basis of GABA receptor-G protein coupling.

G-protein-coupled receptors (GPCRs) have central roles in intercellular communication. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown.

Intraperitoneal injection of lithium chloride induces lateralized activation of the insular cortex in adult mice.

Insular cortex is a critical brain region that participates in the interoceptive sensations. Here, we combined the iDISCO + method and Fos immunostaining to confirm that the middle part of the right-side, but not the left-side, insular cortex in adult male mice is activated by intraperitoneal injection of lithium chloride. Lateralized activation of the insular cortex is also observed in adult female mice, but not in young or aged male mice.

Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E receptor EP2 subtype.

Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E (PGE) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo-electron microscopy structure of the EP2-G complex with its endogenous agonist PGE and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W "toggle switch" and coupling to G via helix 8.

Versatile Functions of Somatostatin and Somatostatin Receptors in the Gastrointestinal System.

Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells, and the inhibitory function of somatostatin-containing cells is involved in a range of physiological functions and pathological modifications. The GI system is the largest endocrine organ for digestion and absorption, SST-endocrine cells and neurons in the GI system are a critical effecter to maintain homeostasis SSTRs 1-5 and co-receptors, while SST-SSTRs are involved in chemo-sensory, mucus, and hormone secretion, motility, inflammation response, itch, and pain the autocrine, paracrine, endocrine, and exoendocrine pathways.

Structural insights into the lipid and ligand regulation of serotonin receptors.

Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter that activates the largest subtype family of G-protein-coupled receptors. Drugs that target 5-HT, 5-HT, 5-HT and other 5-HT receptors are used to treat numerous disorders. 5-HT receptors have high levels of basal activity and are subject to regulation by lipids, but the structural basis for the lipid regulation and basal activation of these receptors and the pan-agonism of 5-HT remains unclear.

Bi-allelic loss of function variants in COX20 gene cause autosomal recessive sensory neuronopathy.

Sensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene.

A substantia innominata-midbrain circuit controls a general aggressive response.

Although aggressive behaviors are universal and essential for survival, "uncontrollable" and abnormal aggressive behaviors in animals or humans may have severe adverse consequences or social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but how brain circuits govern a general aggressive response remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to several aggression-provoking cues with the graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice.