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Category: neuroscience – Page 651

Loss of neurons, not lack of sleep, makes Alzheimer’s patients drowsy

The lethargy that many Alzheimer’s patients experience is caused not by a lack of sleep, but rather by the degeneration of a type of neuron that keeps us awake, according to a study that also confirms the tau protein is behind that neurodegeneration.

The study’s findings contradict the common notion that Alzheimer’s patients during the day to make up for a bad night of sleep and point toward potential therapies to help these patients feel more awake.

The data came from study participants who were patients at UC San Francisco’s Memory and Aging Center and volunteered to have their sleep monitored with electroencephalogram (EEG) and donate their brains after they died.

Neuroscientists Are Confident the Secret to Reversing Brain Damage Is Restoring Brain Plasticity

The Neuro-Network.

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.

Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex

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.

A human genome has finally, fully been decoded

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.

CRISPR/Cas9-engineered Gad1 elimination in rats leads to complex behavioral changes: implications for schizophrenia

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.

Behavioral Consequences of a Combination of Gad1 Haplodeficiency and Adolescent Exposure to an NMDA Receptor Antagonist in Long-Evans Rats

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 finally finish decoding entire human genome in major breakthrough: “We finally got it done”

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.

The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Alzheimer’s Disease

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].