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𝐍𝐞𝐮𝐫𝐨𝐬𝐜𝐢𝐞𝐧𝐭𝐢𝐬𝐭𝐬 𝐀𝐫𝐞 𝐂𝐨𝐧𝐟𝐢𝐝𝐞𝐧𝐭 𝐭𝐡𝐞 𝐒𝐞𝐜𝐫𝐞𝐭 𝐭𝐨 𝐑𝐞𝐯𝐞𝐫𝐬𝐢𝐧𝐠 𝐁𝐫𝐚𝐢𝐧 𝐃𝐚𝐦𝐚𝐠𝐞 𝐈𝐬 𝐑𝐞𝐬𝐭𝐨𝐫𝐢𝐧𝐠 𝐁𝐫𝐚𝐢𝐧 𝐏𝐥𝐚𝐬𝐭𝐢𝐜𝐢𝐭𝐲
𝙁𝙤𝙧 𝙩𝙝𝙚 𝙬𝙤𝙧𝙡𝙙’𝙨 𝙡𝙚𝙖𝙙𝙞𝙣𝙜 𝙣𝙚𝙪𝙧𝙤𝙨𝙘𝙞𝙚𝙣𝙩𝙞𝙨𝙩𝙨, 𝙩𝙝𝙚 𝙨𝙚𝙘𝙧𝙚𝙩 𝙩𝙤 𝙪𝙣𝙡𝙤𝙘𝙠𝙞𝙣… See more.
Stimulating brain plasticity is the key to treatment for the 1.7 million Americans who suffer a traumatic brain injury each year.
Recent advances in multi-electrode array technology have made it possible to monitor large neuronal ensembles at cellular resolution in animal models. In humans, however, current approaches restrict recordings to a few neurons per penetrating electrode or combine the signals of thousands of neurons in local field potential (LFP) recordings. Here we describe a new probe variant and set of techniques that enable simultaneous recording from over 200 well-isolated cortical singl… See more.
Neuropixels probes were used to simultaneously record from more than 200 cortical neurons in human participants during neurosurgical procedures. The approach could reveal insights underlying human cognition and pathology.
Further study of newly-sequenced portions of the genome could also help scientists better understand how humans evolved particular traits, such as the bigger brains that sent them down a genetically distinct path from their great ape ancestors.
“The things that make our frontal cortex bigger come from the genes that map in these repetitive regions,” said Evan Eichler, a professor in the department of genome sciences at the University of Washington School of Medicine and also part of the research collaborative.
Advances in genomic sequencing technology could drive a renaissance of medical breakthroughs, the researchers say.
GABAergic dysfunctions have been implicated in the pathogenesis of schizophrenia, especially the associated cognitive impairments. The GABA synthetic enzyme glutamate decarboxylase 67-kDa isoform (GAD67) encoded by the GAD1 gene is downregulated in the brains of patients with schizophrenia. Furthermore, a patient with schizophrenia harboring a homozygous mutation of GAD1 has recently been discovered. However, it remains unclear whether loss of function of GAD1 leads to the symptoms observed in schizophrenia, including cognitive impairment. One of the obstacles faced in experimental studies to address this issue is the perinatal lethality of Gad1 knockout (KO) mice, which precluded characterization at the adult stage. In the present study, we successfully generated Gad1 KO rats using CRISPR/Cas9 genome editing technology.
Glutamate decarboxylase 67-kDa isoform (GAD67), which is encoded by the GAD1 gene, is one of the key enzymes that produce GABA. The reduced expression of GAD67 has been linked to the pathophysiology of schizophrenia. Additionally, the excitatory glutamatergic system plays an important role in the development of this disorder. Animal model studies have revealed that chronic blockade of NMDA-type glutamate receptors can cause GABAergic dysfunction and long-lasting behavioral abnormalities. Based on these findings, we speculated that Gad1 haplodeficiency combined with chronic NMDA receptor blockade would lead to larger behavioral consequences relevant to schizophrenia in a rat model. In this study, we administered an NMDAR antagonist, MK-801 (0.2 mg/kg), to CRISPR/Cas9-generated Gad1+/− rats during adolescence to test this hypothesis. The MK-801 treated Gad1+/− rats showed a shorter duration in each rearing episode in the open field test than the saline-treated Gad1+/+ rats. In contrast, immobility in the forced swim test was increased and fear extinction was impaired in Gad1+/− rats irrespective of MK-801 treatment. Interestingly, the time spent in the center region of the elevated plus-maze was significantly affected only in the saline-treated Gad1+/− rats. Additionally, the MK-801-induced impairment of the social novelty preference was not observed in Gad1+/− rats. These results suggest that the synergistic and additive effects of Gad1 haplodeficiency and NMDA receptor blockade during adolescence on the pathogenesis of schizophrenia may be more limited than expected. Findings from this study also imply that these two factors mainly affect negative or affective symptoms, rather than positive symptoms.
γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the central nervous system (Obata, 2013). Post-mortem brain studies on schizophrenia have shown that GABAergic disturbances are part of the pathophysiology of the disorder (Lewis and Sweet, 2009). In particular, the expression level of the GABA-synthesizing enzyme glutamate decarboxylase 67-kDa isoform (GAD67) is lower in the cerebral cortex of patients with schizophrenia than in that of healthy subjects (Guidotti et al., 2000; Volk et al., 2000; Hashimoto et al., 2003; Hashimoto et al., 2008; Curley et al., 2011). GAD67 is encoded by the GAD1 gene, whose SNPs are also suggested to be risk factors for schizophrenia (Addington et al., 2005). We previously reported that Gad1−/− rats displayed some schizophrenia-relevant behaviors, including working memory, which is important for the functional outcome of schizophrenia (Fujihara et al., 2020a).
Scientists said this full picture of the genome will give humanity a greater understanding of our evolution and biology while also opening the door to medical discoveries in areas like aging, neurodegenerative conditions, cancer and heart disease.
“We’re just broadening our opportunities to understand human disease,” said Karen Miga, an author of one of the six studies published Thursday.
The research caps off decades of work. The first draft of the human genome was announced in a White House ceremony in 2000 by leaders of two competing entities: an international publicly funded project led by an agency of the U.S. National Institutes of Health and a private company, Maryland-based Celera Genomics.
Despite a wealth of knowledge gained in the past three decades concerning the molecular underpinnings of Alzheimer’s disease (AD), progress towards obtaining effective, disease modifying therapies has proven to be challenging. In this manner, numerous clinical trials targeting the production, aggregation, and toxicity of beta-amyloid, have failed to meet efficacy standards. This puts into question the beta-amyloid hypothesis and suggests that additional treatment strategies should be explored. The recent emergence of CRISPR/Cas9 gene editing as a relatively straightforward, inexpensive, and precise system has led to an increased interest of applying this technique in AD. CRISPR/Cas9 gene editing can be used as a direct treatment approach or to help establish better animal models that more faithfully mimic human neurodegenerative diseases. In this manner, this technique has already shown promise in other neurological disorders, such as Huntington’s disease. The purpose of this review is to examine the potential utility of CRISPR/Cas9 as a treatment option for AD by targeting specific genes including those that cause early-onset AD, as well as those that are significant risk factors for late-onset AD such as the apolipoprotein E4 (APOE4) gene.
Keywords: Alzheimer’s disease, CRISPR/Cas9, Gene editing, Treatment, Huntington’s disease, iPSC neurons.
Alzheimer’s Disease (AD) is a progressive and fatal neurodegenerative disorder that primarily affects older adults and is the most common cause of dementia [1]. Currently it afflicts 5.5 million Americans and that number is expected to triple by 2050. At the present time, it is the third leading cause of death behind heart disease and cancer, with an estimated 700,000 Americans ages65 years will have AD when they die [2]. In addition, the cost of the disease is substantial with $259 billion health care dollars going to manage the disease currently, and by the middle of the century costs are predicted to soar over $1.2 trillion, which will completely bankrupt the healthcare system in the USA [3]. Worldwide, 47 million people live with dementia and that number is projected to increase to more than 131 million by 2050 with an estimated worldwide cost of US $818 billion [4].
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The Neuro-Network.
𝐄𝐧𝐳𝐲𝐦𝐞 𝐛𝐥𝐨𝐜𝐤𝐞𝐫 𝐜𝐨𝐮𝐥𝐝 𝐨𝐩𝐞𝐧 𝐧𝐞𝐰 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭𝐬 𝐟𝐨𝐫 𝐧𝐞𝐮𝐫𝐨𝐝𝐞𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐯𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬
𝙍𝙚𝙨𝙚𝙖𝙧𝙘𝙝𝙚𝙧𝙨 𝙝𝙖𝙫𝙚 𝙪𝙣𝙘𝙤𝙫𝙚𝙧𝙚𝙙 𝙝𝙤𝙬 𝙖 𝙘𝙚𝙧𝙩𝙖𝙞𝙣 𝙢𝙤𝙡𝙚𝙘𝙪𝙡𝙖𝙧 𝙥𝙖𝙩𝙝𝙬𝙖𝙮 𝙩𝙧𝙞𝙜𝙜𝙚𝙧𝙨 𝙩𝙝𝙚 𝙗𝙧𝙚𝙖𝙠𝙙𝙤𝙬𝙣 𝙤𝙛 𝙣𝙚𝙧… See more.
Researchers have uncovered how a certain molecular pathway triggers the breakdown of nerve fibers in neurodegenerative diseases – and more importantly, how to potentially switch it off. The find could lead to a new class of drugs that slows the progression of these debilitating disorders.
The focus of the study was an enzyme called SARM1, which is expressed in neurons and plays a role as an immune regulator. However, it also functions as a sensor of metabolic stress, and at a certain point it sparks a cascade of processes that eventually begins to break down axons, leading to some of the issues associated with Parkinson’s disease, ALS, neuropathy, and other neurodegenerative diseases.