Neuroscience Insights最新文献

{"title":"Progression of Cognitive Impairment to Alzheimer's Disease: Through the Lens of Salivary Extracellular Vesicles.","authors":"Simran Rastogi,&nbsp;Komal Rani,&nbsp;Saroj Kumar","doi":"10.1177/26331055211058687","DOIUrl":"https://doi.org/10.1177/26331055211058687","url":null,"abstract":"<p><p>The elusiveness encircling around the domain of cognition, its impairment, and the poor prognosis of Alzheimer's disease has made early diagnosis a necessity. The noticeable symptoms in these conditions appear years later after the neuropathological changes occur in the brain. Exosomes, a small-sized extracellular vesicle facilitate intercellular communication of disease pathologies and their cargo can provide molecular information about its place of origin. The study titled \"A novel approach to correlate the salivary exosomes and their protein cargo in the progression of cognitive impairment into Alzheimer's disease\" was an attempt toward understanding the role of salivary small-sized extracellular vesicular (EV's) cargo in monitoring the progression. Outcomes of the study represent, that the salivary small-sized EV's (ssEV's) levels were higher in the cognitively impaired and Alzheimer's diseased as well the differential expression of the protein in the cargo correlates well with the disease severity staging. Thus, it can help in the development of an early non-invasive screening method.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211058687"},"PeriodicalIF":3.6,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/d9/10.1177_26331055211058687.PMC8637705.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39696530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Spanish Composer Manuel de Falla and His Eyes: The Musical Brain.","authors":"Alicia García-Falgueras,&nbsp;Dick F Swaab","doi":"10.1177/26331055211049778","DOIUrl":"https://doi.org/10.1177/26331055211049778","url":null,"abstract":"<p><p>Manuel de Falla was a Spanish musician of the XIXth and XXth centuries who had international recognition likely due to his musical fusion talent. His knowledge about Spanish musical traditions gave to his early compositions a new and fresh intellectual interpretation for the typical Spanish folk music. However, in the middle of his musical career, he suffered a strange disease of his eyes named recurrent acute iridocyclitis. This eye flushing is caused by an inflammation of 2 structures of the anterior pole of the ocular globe, the iris, and the ciliary body. It is usually a symptom of another disease and it causes many psychological impairments and disabilities (severe eye pain in bright light, blurry vision, headache, stress for organization (orderliness), and depression in some cases). This soreness of his eyes had an effect over Falla's compositions and marked an inflection point in his line of musical creations. Eyes in music have been so relevant in another composers and musicians throughout history.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211049778"},"PeriodicalIF":3.6,"publicationDate":"2021-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/b2/10.1177_26331055211049778.PMC8552372.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39581236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Safer Psychedelics for Treating Addiction.","authors":"Jamie Peters,&nbsp;David E Olson","doi":"10.1177/26331055211033847","DOIUrl":"https://doi.org/10.1177/26331055211033847","url":null,"abstract":"<p><p>Addiction is best described as a disorder of maladaptive neuroplasticity involving the simultaneous strengthening of reward circuitry that drives compulsive drug seeking and weakening of circuits involved in executive control over harmful behaviors. Psychedelics have shown great promise for treating addiction, with many people attributing their therapeutic effects to insights gained while under the influence of the drug. However, psychedelics are also potent psychoplastogens-molecules capable of rapidly re-wiring the adult brain. The advent of non-hallucinogenic psychoplastogens with anti-addictive properties raises the intriguing possibility that hallucinations might not be necessary for all therapeutic effects of psychedelic-based medicines, so long as the underlying pathological neural circuitry can be remedied. One of these non-hallucinogenic psychoplastogens, tabernanthalog (TBG), appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction. Here, we discuss the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211033847"},"PeriodicalIF":3.6,"publicationDate":"2021-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211033847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39277625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vagus Nerve Stimulation Ameliorates Cognitive Impairment and Increased Hippocampal Astrocytes in a Mouse Model of Gulf War Illness.","authors":"Lavanya Venkatasamy,&nbsp;Damir Nizamutdinov,&nbsp;Jaclyn Jenkins,&nbsp;Lee A Shapiro","doi":"10.1177/26331055211018456","DOIUrl":"https://doi.org/10.1177/26331055211018456","url":null,"abstract":"<p><p>Gulf war illness (GWI), is a chronic multi-symptom illness that has impacted approximately one-third of the veterans who served in the 1990 to 1991 Gulf War. GWI symptoms include cognitive impairments (eg, memory and concentration problems), headaches, migraines, fatigue, gastrointestinal and respiratory issues, as well as emotional deficits. The exposure to neurological chemicals such as the anti-nerve gas drug, pyridostigmine bromide (PB), and the insecticide permethrin (PER), may contribute to the etiologically related factors of GWI. Various studies utilizing mouse models of GWI have reported the interplay of these chemical agents in increasing neuroinflammation and cognitive dysfunction. Astrocytes are involved in the secretion of neuroinflammatory cytokines and chemokines in pathological conditions and have been implicated in GWI symptomology. We hypothesized that exposure to PB and PER causes lasting changes to hippocampal astrocytes, concurrent with chronic cognitive deficits that can be reversed by cervical vagus nerve stimulation (VNS). GWI was induced in CD1 mice by injecting the mixture of PER (200 mg/kg) and PB (2 mg/kg), i.p. for 10 consecutive days. VNS stimulators were implanted at 33 weeks after GWI induction. The results show age-related cognitive alterations at approximately 9 months after exposure to PB and PER. The results also showed an increased number of GFAP-labeled astrocytes in the hippocampus and dentate gyrus that was ameliorated by VNS.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211018456"},"PeriodicalIF":3.6,"publicationDate":"2021-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211018456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39076275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is There a Brain Microbiome?","authors":"Christopher D Link","doi":"10.1177/26331055211018709","DOIUrl":"https://doi.org/10.1177/26331055211018709","url":null,"abstract":"<p><p>Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the \"ground truth\" of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a \"brain microbiome.\"</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211018709"},"PeriodicalIF":3.6,"publicationDate":"2021-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211018709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38995912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive Immune Responses Associated with the Central Nervous System Pathology of Gulf War Illness.","authors":"Aurore Nkiliza,&nbsp;Utsav Joshi,&nbsp;James E Evans,&nbsp;Ghania Ait-Ghezala,&nbsp;Megan Parks,&nbsp;Fiona Crawford,&nbsp;Michael Mullan,&nbsp;Laila Abdullah","doi":"10.1177/26331055211018458","DOIUrl":"https://doi.org/10.1177/26331055211018458","url":null,"abstract":"<p><p>Gulf War Illness is a multisymptomatic condition which affects 30% of veterans from the 1991 Gulf War. While there is evidence for a role of peripheral cellular and humoral adaptive immune responses in Gulf War Illness, a potential role of the adaptive immune system in the central nervous system pathology of this condition remains unknown. Furthermore, many of the clinical features of Gulf War Illness resembles those of autoimmune diseases, but the biological processes are likely different as the etiology of Gulf War Illness is linked to hazardous chemical exposures specific to the Gulf War theatre. This review discusses Gulf War chemical-induced maladaptive immune responses and a potential role of cellular and humoral immune responses that may be relevant to the central nervous system symptoms and pathology of Gulf War Illness. The discussion may stimulate investigations into adaptive immunity for developing novel therapies for Gulf War Illness.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211018458"},"PeriodicalIF":3.6,"publicationDate":"2021-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211018458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38995911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Carbamate, Physostigmine does not Impair Axonal Transport in Rat Cortical Neurons.","authors":"Sean X Naughton,&nbsp;Wayne D Beck,&nbsp;Zhe Wei,&nbsp;Guangyu Wu,&nbsp;Peter W Baas,&nbsp;Alvin V Terry","doi":"10.1177/26331055211020289","DOIUrl":"https://doi.org/10.1177/26331055211020289","url":null,"abstract":"<p><p>Among the various chemicals that are commonly used as pesticides, organophosphates (OPs), and to a lesser extent, carbamates, are most frequently associated with adverse long-term neurological consequences. OPs and the carbamate, pyridostigmine, used as a prophylactic drug against potential nerve agent attacks, have also been implicated in Gulf War Illness (GWI), which is often characterized by chronic neurological symptoms. While most OP- and carbamate-based pesticides, and pyridostigmine are relatively potent acetylcholinesterase inhibitors (AChEIs), this toxicological mechanism is inadequate to explain their long-term health effects, especially when no signs of acute cholinergic toxicity are exhibited. Our previous work suggests that a potential mechanism of the long-term neurological deficits associated with OPs is impairment of axonal transport (AXT); however, we had not previously evaluated carbamates for this effect. Here we thus evaluated the carbamate, physostigmine (PHY), a highly potent AChEI, on AXT using an <i>in vitro</i> neuronal live imaging assay that we have previously found to be very sensitive to OP-related deficits in AXT. We first evaluated the OP, diisopropylfluorophosphate (DFP) (concentration range 0.001-10.0 µM) as a reference compound that we found previously to impair AXT and subsequently evaluated PHY (concentration range 0.01-100 nM). As expected, DFP impaired AXT in a concentration-dependent manner, replicating our previously published results. In contrast, none of the concentrations of PHY (including concentrations well above the threshold for impairing AChE) impaired AXT. These data suggest that the long-term neurological deficits associated with some carbamates are not likely due to acute impairments of AXT.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211020289"},"PeriodicalIF":3.6,"publicationDate":"2021-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211020289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38996339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilateral Hypertrophic Olivary Degeneration Following Brainstem Insult: A Retrospective Review and Examination of Causative Pathology.","authors":"Fardad Behzadi,&nbsp;Peter J Fiester,&nbsp;Dinesh Rao","doi":"10.1177/26331055211007445","DOIUrl":"https://doi.org/10.1177/26331055211007445","url":null,"abstract":"<p><p>Hypertrophic olivary degeneration is a rare condition caused by a lesion in the Guillain-Mollaret triangle which leads to trans-synaptic degeneration resulting in the degenerative hypertrophy of the inferior olivary nucleus. This condition presents clinically with palatal tremor but can also produce ocular myoclonus or cerebellar signs. While any lesion that occurs within the Guillian-Mollaret triangle and results in the deafferentation of the inferior olive can lead to hypertrophic olivary degeneration, the most common etiologies include ischemic and hemorrhagic stroke, vascular malformation, neoplasm, and iatrogenic injury related to surgery. We report a series of 7 patients who presented with this condition bilaterally on MRI imaging, including 1 case which represents the first report of toxoplasmosis leading to the development of bilateral hypertrophic olivary degeneration and only the third reported case, unilateral or bilateral, related to an infectious etiology.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211007445"},"PeriodicalIF":3.6,"publicationDate":"2021-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211007445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39390027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glut1 deficiency syndrome: New and emerging insights into a prototypical brain energy failure disorder.","authors":"Maoxue Tang,&nbsp;Umrao R Monani","doi":"10.1177/26331055211011507","DOIUrl":"https://doi.org/10.1177/26331055211011507","url":null,"abstract":"<p><p>Considering its small size relative to the rest of the body, the mammalian brain has a disproportionately high energy requirement. This energy is supplied to the brain mainly in the form of glucose through the principal cerebral glucose transporter, Glut1. Inactivation of even a single copy of the Glut1 gene, <i>SLC2A1</i>, has dire consequences for the brain, starving cerebral neurons of energy and triggering the debilitating neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). Considering the monogenic nature of Glut1 DS, the disease serves as an excellent paradigm to study the larger family of brain energy failure syndromes. Here we review how studies of Glut1 DS are proving instructive to the brain's energy needs, focusing first on the requirements, both spatial and temporal of the transporter, second, on proposed mechanisms linking low Glut1 to brain dysfunction and, finally on efforts to treat the disease and thus restore nutritional support to the brain. These studies promise not only to inform mechanisms and treatments for the relatively rare Glut1 DS but also the myriad other conditions involving the Glut1 protein.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211011507"},"PeriodicalIF":3.6,"publicationDate":"2021-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211011507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39494843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binge-Like Ethanol Drinking Increases <i>Otx2</i>, <i>Wnt1</i>, and <i>Mdk</i> Gene Expression in the Ventral Tegmental Area of Adult Mice.","authors":"Cassandre Coles,&nbsp;Amy W Lasek","doi":"10.1177/26331055211009850","DOIUrl":"https://doi.org/10.1177/26331055211009850","url":null,"abstract":"<p><p>Alcohol use disorder is associated with pathophysiological changes in the dopaminergic system. Orthodenticle homeobox 2 (OTX2) is a transcription factor important for the development of dopaminergic neurons residing in the ventral tegmental area (VTA), a critical region of the brain involved in drug reinforcement. Previous studies have demonstrated that ethanol exposure during embryonic development reduces <i>Otx2</i> mRNA levels in the central nervous system. We hypothesized that levels of OTX2 would be altered by binge-like ethanol consumption in adult animals. To test this, <i>Otx2</i> mRNA and protein levels in the mouse VTA were measured by quantitative real-time PCR and western blotting, respectively, after mice drank ethanol for 4 days in a procedure that elicits binge levels of ethanol consumption (drinking in the dark). Expression of known and putative OTX2 transcriptional target genes (<i>Sema3c</i>, <i>Wnt1</i>, and <i>Mdk</i>) were also measured in the VTA after ethanol drinking. <i>Otx2</i> mRNA and protein levels were elevated in the VTA 24 hours after the fourth drinking session and there was a corresponding increase in the expression of <i>Mdk</i> transcript. Interestingly, <i>Wnt1</i> transcript was elevated in the VTA immediately after the fourth drinking session but returned to control levels 24 hours later. We next investigated if viral-mediated reduction of <i>Otx2</i> in the mouse VTA would alter ethanol or sucrose intake. Lentiviral vectors expressing a shRNA targeting <i>Otx2</i> or a control shRNA were injected into the VTA and mice were tested in the drinking in the dark protocol for ethanol and sucrose drinking. Reducing levels of OTX2 in the VTA did not alter ethanol or sucrose consumption. One limitation is that the extent of OTX2 reduction may not have been sufficient. Although OTX2 in the VTA may not play a role in binge-like drinking in adult mice, OTX2 could contribute to ethanol-induced transcriptional changes in this region.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":"26331055211009850"},"PeriodicalIF":3.6,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211009850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38874031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}