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Autism spectrum disorder:difficulties in diagnosis and microRNA biomarkers

Neural Regeneration Research 2025年第10期20卷 2776-2786页

作者： bridget martinez Philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear *** of the studies involved children and the study cohorts were largely *** of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA *** five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to *** microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of *** important limitations were identified in the studies reviewed,and need to be taken into account in future *** studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.

关键词： autism spectrum disorder biomarker blood cells blood plasma blood serum diagnosis microRNA peripheral blood mononuclear cells serum neural cell adhesion molecule L1-captured extracellular vesicles whole blood

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MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration Research 2025年第6期20卷 1681-1695页

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed i

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular vesicles/exosomes blood serum brain tissue brain tissue extracellular vesicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

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MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

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Neural Regeneration Research 2025年第7期20卷 1957-1970页

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life ***,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress *** addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate *** suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress *** performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December *** included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum *** of these studies had also used whole *** studies were excluded as they did not involve microRNA *** of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult *** measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString *** six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to *** miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/

关键词： biomarker diagnosis microRNA peripheral blood mononuclear cells plasma extracellular vesicles/exosomes post-traumatic stress disorder serum exosomes whole blood whole plasma

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MicroRNAs as diagnostic and prognostic biomarkers of age-related macular degeneration:advances and limitations

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Neural Regeneration Research 2021年第3期16卷 440-447页

作者： bridget martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.George’s University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

A main cause of vision loss in the elderly is age-related macular degeneration(AMD).Among the cellular,biochemical,and molecular changes linked to this disease,inflammation and angiogenesis appear as being crucial in AMD pathogenesis and *** are two forms of the disease:dry AMD,accounting for 80–90%of cases,and wet *** disease usually begins as dry AMD associated with retinal pigment epithelium and photoreceptor degeneration,whereas wet AMD is associated with choroidal neovascularization resulting in severe vision *** new vessels are largely malformed,leading to blood and fluid leakage within the disrupted tissue,which provokes inflammation and scar formation and results in retinal damage and *** RNAs are dysregulated in AMD and may facilitate the early detection of the disease and monitoring disease *** recent reviews of micro RNAs in AMD had indicated weaknesses or limitations in four earlier *** in the last three years have shown considerable progress in overcoming some of these concerns and identifying specific micro RNAs as biomarkers for *** large-scale studies are warranted using appropriate statistical methods to take into account gender and age disparity in the study populations and confounding factors such as smoking status.

关键词： biomarkers blood plasma blood serum macular degeneration microRNAs peripheral blood nuclear cells retinal tissues vitreous humour whole blood

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MicroRNA biomarkers in frontotemporal dementia and to distinguish from Alzheimer's disease and amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第7期17卷 1412-1422页

作者： bridget martinez Philip V.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal *** lobar degeneration is considered to be equivalent to frontotemporal *** dementia is characterized by progressive impairments in behavior,executive function,and *** are two main clinical subtypes:behavioral-variant frontotemporal dementia and primary progressive *** early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these *** validated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric *** the studies reviewed a very large number of microRNAs were found to be dysregulated but with limited overlap between individual *** of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral ***,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behavioral-variant frontotemporal dementia from healthy *** of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectively,from healthy *** strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal *** miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia *** studies are

关键词： Alzheimer’s disease amyotrophic lateral sclerosis behavioral variant biomarker blood plasma blood serum brain cerebrospinal fluid cortical tissue frontotemporal dementia frontotemporal lobar degeneration microRNA primary progressive aphasia

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Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies

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Neural Regeneration Research 2021年第11期16卷 2159-2169页

作者： bridget martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex,and which were mostly *** the altered microRNAs were miR-9/9*,miR-29b,miR-124a,miR-132,miR-128,miR-139,miR-122,miR-138,miR-23b,miR-135b,miR-181(all downregulated)and miR-448(upregulated),and similar changes had been previously found in Huntington’s disease *** the animal cell studies,the altered microRNAs included miR-9,miR-9*,miR-135b,miR-222(all downregulated)and miR-214(upregulated).In the animal models,overexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein level,lowered the mutant huntingtin aggregates in striatum and cortex,and improved performance in behavioral *** performance in behavioral tests also occurred with overexpression of miR-132 and *** the animal cell models,overexpression of miR-22 increased the viability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin-enriched foci of≥2μ***,overexpression of miR-22 enhanced the survival of rat primary striatal neurons treated with 3-nitropropionic *** expression of miR-214,miR-146a,miR-150,and miR-125b decreased endogenous expression of huntingtin mRNA and protein in HdhQ111/HdhQ111 *** studies with animal models of Huntington’s disease are warranted to validate these findings and identify specific microRNAs whose overexpression inhibits the production of mutant huntingtin protein and other harmful processes and may provide a more effective means of treating Huntington’s disease in patients and slowing its progression.

关键词： animal model cerebral cortex huntingtin Huntington’s disease microRNA neurodegeneration striatum therapeutic strategies

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MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

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Neural Regeneration Research 2024年第3期19卷 557-562页

作者： bridget martinez Philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoUSA Department of Medicine University of Nevada-RenoRenoUSA Department of Anatomy University of OtagoDunedinNew Zealand

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric *** cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not *** diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are *** for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure *** is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be *** expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity *** recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual *** the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood *** studies are warranted with children and adults with attention deficit hyperactivity disorder,and

关键词： adults attention deficit hyperactivity disorder biomarkers blood plasma blood serum children microRNA total white blood cells whole blood

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MicroRNAs as biomarkers in glaucoma and potential therapeutic targets

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Neural Regeneration Research 2022年第11期17卷 2368-2375页

Glaucoma is a neurodegenerative disease in which optic nerve damage and visual field defects *** is a leading cause of irreversible *** pathogenesis is largely unknown although several risk factors have been identified,with an increase in intraocular pressure being the main *** of intraocular pressure is the only treatment ***-angle glaucoma is the most common form of the condition,accounting for~90%of all cases of glaucoma,with primary open-angle glaucoma and exfoliation glaucoma being the most frequent *** are strong indications that microRNAs play important roles in the pathogenesis of primary open-angle *** of the recent studies reviewed had performed microRNA profiling in aqueous humor from glaucoma patients compared to controls who were chiefly cataract patients.A very large number of microRNAs were dysregulated but with limited overlap between individual *** in aqueous humor that could be possible targets for therapeutic intervention are miR-143-3p,miR-125b-5p,and *** ove rlap of findings occurred within the dysregulated miRNAs for blood plasma,blood serum,peripheral blood mononuclear cells,and tears of primary open-angle glaucoma *** ral impo rtant limitations were identified in these *** studies are warranted of mic roRNA expression in aqueous humor and blood samples of primary open-angle glaucoma patients in the early stages of the disease so that validated biomarkers can be identified and treatment *** addition,whether modifying the levels of specific microRNAs in aqueous humor or tears has a beneficial effect on intraocular pressure and ophthalmic examination of the eyes should be investigated using suitable animal models of glaucoma.

关键词： aqueous humor biomarkers blood plasma blood serum glaucoma intraocular pressure microRNA peripheral blood mononuclear cells tears therapeutic targets

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Protective effects of pharmacological therapies in animal models of multiple sclerosis: a review of studies 2014–2019

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Neural Regeneration Research 2020年第7期15卷 1220-1234页

作者： bridget martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineTrue BlueGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous *** disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is *** there is considerable loss of axons,MS patients enter a secondary progressive ***-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive *** animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to *** experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's *** clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and *** the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis *** all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.

关键词： animal models autoimmune encephalomyelitis disease cuprizone-induced toxicity multiple sclerosis neurodegeneration neuroinflammation neuroprotection pharmacological agents progressive disease Theiler's murine encephalomyelitis virus

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MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

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Neural Regeneration Research 2023年第10期18卷 2108-2118页

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

关键词： epilepsy experimental models microRNA mouse rat seizures therapeutic targets

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