Pub Date : 2024-01-01DOI: 10.46439/neurobiology.5.026
Boris Tabakoff, Paula L Hoffman, Laura M Saba
<p><strong>Background: </strong>At the invitation of the Journal, we are providing a summary of our published work that has followed the publication in 2009 of our manuscript entitled "Genetical Genomic Determinants of Alcohol Consumption in Rats and Humans". Our initial premise, which has been maintained throughout, is that knowledge regarding gene transcription would greatly enhance GWAS of alcohol-related phenotypes. We chose to concentrate our studies on the quantitative phenotype of alcohol consumption since high levels of alcohol consumption are a prerequisite for the development of alcohol use disorder (AUD). We also structured our studies to focus on "predisposition" to higher levels of alcohol consumption. We defined predisposition as a genetic structure and transcriptional pattern that is inherent in an organism and present prior to exposure to an environmental stimulus that engenders a physiological/behavioral response. In studies using humans, this interest in predisposition usually requires prolonged periods of cohort follow-up. On the other hand, studies with animals can use resources such as panels of recombinant inbred (RI) animals (in our case, the HXB/BXH rat panel) to capture the transcriptional landscape of animals not exposed to alcohol and compare this transcriptional landscape to levels of alcohol consumption collected from a different cohort of animals that are the same age, have an identical genetic composition, and are raised in an identical environment. The other benefit is that the stable genetic structure of inbred strains allows for a chronological expansion of information on these animals. This characteristic of the HXB/BXH RI rats allowed us to add important information as technology and analytical methods developed over time.</p><p><strong>Methods findings and conclusions: </strong>Our initial studies relied on hybridization arrays for RNA quantification in brain, an initial set of polymorphic markers for the rat genome, and a standard behavioral (b)QTL analysis for alcohol consumption. What we added to the conceptual basis for analysis and interpretation was the calculation of transcript expression (e)QTLs and the requirements that: 1. the eQTL overlapped the location of the bQTL; and 2. the transcript levels were significantly correlated with the quantitative levels of alcohol consumption across rat strains. These criteria were used to identify genes (transcripts) as "candidate" contributors to the alcohol consumption phenotype. We soon realized that the search for candidate genes as unique determinants of a complex trait is irrational, since these phenotypes are best characterized by differences in genetic networks. Therefore, we incorporated Weighted Gene Coexpression Network Analysis (WGCNA) in our further work. We also realized the limitations of hybridization arrays for breadth of transcriptome coverage and quantification, and in the more current work used total RNA-Seq-derived data for characterizing nearl
{"title":"The genetical genomic path to understanding why rats and humans consume too much alcohol.","authors":"Boris Tabakoff, Paula L Hoffman, Laura M Saba","doi":"10.46439/neurobiology.5.026","DOIUrl":"https://doi.org/10.46439/neurobiology.5.026","url":null,"abstract":"<p><strong>Background: </strong>At the invitation of the Journal, we are providing a summary of our published work that has followed the publication in 2009 of our manuscript entitled \"Genetical Genomic Determinants of Alcohol Consumption in Rats and Humans\". Our initial premise, which has been maintained throughout, is that knowledge regarding gene transcription would greatly enhance GWAS of alcohol-related phenotypes. We chose to concentrate our studies on the quantitative phenotype of alcohol consumption since high levels of alcohol consumption are a prerequisite for the development of alcohol use disorder (AUD). We also structured our studies to focus on \"predisposition\" to higher levels of alcohol consumption. We defined predisposition as a genetic structure and transcriptional pattern that is inherent in an organism and present prior to exposure to an environmental stimulus that engenders a physiological/behavioral response. In studies using humans, this interest in predisposition usually requires prolonged periods of cohort follow-up. On the other hand, studies with animals can use resources such as panels of recombinant inbred (RI) animals (in our case, the HXB/BXH rat panel) to capture the transcriptional landscape of animals not exposed to alcohol and compare this transcriptional landscape to levels of alcohol consumption collected from a different cohort of animals that are the same age, have an identical genetic composition, and are raised in an identical environment. The other benefit is that the stable genetic structure of inbred strains allows for a chronological expansion of information on these animals. This characteristic of the HXB/BXH RI rats allowed us to add important information as technology and analytical methods developed over time.</p><p><strong>Methods findings and conclusions: </strong>Our initial studies relied on hybridization arrays for RNA quantification in brain, an initial set of polymorphic markers for the rat genome, and a standard behavioral (b)QTL analysis for alcohol consumption. What we added to the conceptual basis for analysis and interpretation was the calculation of transcript expression (e)QTLs and the requirements that: 1. the eQTL overlapped the location of the bQTL; and 2. the transcript levels were significantly correlated with the quantitative levels of alcohol consumption across rat strains. These criteria were used to identify genes (transcripts) as \"candidate\" contributors to the alcohol consumption phenotype. We soon realized that the search for candidate genes as unique determinants of a complex trait is irrational, since these phenotypes are best characterized by differences in genetic networks. Therefore, we incorporated Weighted Gene Coexpression Network Analysis (WGCNA) in our further work. We also realized the limitations of hybridization arrays for breadth of transcriptome coverage and quantification, and in the more current work used total RNA-Seq-derived data for characterizing nearl","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":"5 1","pages":"15-22"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029836","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}
Pub Date : 2023-12-21DOI: 10.46439/neurobiology.5.024
N’Dré Jean N’DRE, P. A. Lecor, Assoumou Aa, Blohoua Mjj
Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.
{"title":"Evaluation of chondrocyte dedifferentiation mechanisms using confocal Raman microscopy","authors":"N’Dré Jean N’DRE, P. A. Lecor, Assoumou Aa, Blohoua Mjj","doi":"10.46439/neurobiology.5.024","DOIUrl":"https://doi.org/10.46439/neurobiology.5.024","url":null,"abstract":"Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":"135 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-31DOI: 10.46439/neurobiology.4.022
{"title":"Systematic evaluation of the effects of exenatide and liraglutide on neurodegenerative diseases induced by type 2 diabetes mellitus","authors":"","doi":"10.46439/neurobiology.4.022","DOIUrl":"https://doi.org/10.46439/neurobiology.4.022","url":null,"abstract":"","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43758896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-31DOI: 10.46439/neurobiology.4.019
{"title":"The surgical philosophy for the management of rathke cleft cyst: Finding the sweet spot","authors":"","doi":"10.46439/neurobiology.4.019","DOIUrl":"https://doi.org/10.46439/neurobiology.4.019","url":null,"abstract":"","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48275419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-16DOI: 10.46439/neurobiology.4.023
Phillip Johansen, B. Lucke-Wold
Mehkri et al. have presented a thorough review of calcitonin-gene related peptide (CGRP) and its relationship with headaches, both primary (e.g., migraine headaches) and secondary headaches (e.g., headaches secondary to subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI)) [1]. They have provided an accurate depiction of the literature and the current knowledge regarding CGRP’s association with neurologic injury, as well as some of the physiologic mechanisms and therapeutic targets. This commentary aims to further discuss the veracity of this article and to add an alternative viewpoint in terms of neuromodulators influencing post-traumatic headaches (PTH). Regarding PTH, the authors accurately depict a current understanding that is grounded in literature – CGRP’s association with neurologic injury is incompletely understood. Whether it be intracellular signaling leading to a pseudo-inflammatory response or hyperstimulation of the brain, CGRP is known to exacerbate headache symptoms. However, CGRP’s interactions in the setting of secondary headaches, such as those induced by subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI), are variable depending on the timeframe. CGRP is thought to be neuroprotective in the acute setting time, CGRP levels normalize despite low-to-normal levels, patients with hypersensitized thorough
{"title":"Commentary on “Calcitonin-gene related peptide and neurologic injury: An emerging target for headache management”","authors":"Phillip Johansen, B. Lucke-Wold","doi":"10.46439/neurobiology.4.023","DOIUrl":"https://doi.org/10.46439/neurobiology.4.023","url":null,"abstract":"Mehkri et al. have presented a thorough review of calcitonin-gene related peptide (CGRP) and its relationship with headaches, both primary (e.g., migraine headaches) and secondary headaches (e.g., headaches secondary to subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI)) [1]. They have provided an accurate depiction of the literature and the current knowledge regarding CGRP’s association with neurologic injury, as well as some of the physiologic mechanisms and therapeutic targets. This commentary aims to further discuss the veracity of this article and to add an alternative viewpoint in terms of neuromodulators influencing post-traumatic headaches (PTH). Regarding PTH, the authors accurately depict a current understanding that is grounded in literature – CGRP’s association with neurologic injury is incompletely understood. Whether it be intracellular signaling leading to a pseudo-inflammatory response or hyperstimulation of the brain, CGRP is known to exacerbate headache symptoms. However, CGRP’s interactions in the setting of secondary headaches, such as those induced by subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI), are variable depending on the timeframe. CGRP is thought to be neuroprotective in the acute setting time, CGRP levels normalize despite low-to-normal levels, patients with hypersensitized thorough","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":"4 1","pages":"20 - 22"},"PeriodicalIF":0.0,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44645873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-10DOI: 10.46439/neurobiology.4.020
Sophia Cai, Min Woo Kim, Pan Chen
Although essential metal ions are required in the body, neurotoxicity occurs when exposed to a concentration of metal that the body cannot accommodate. In the case of non-essential metals which are important in industry, these elements have the property of causing neurotoxicity even at small concentrations. When such neurotoxicity progresses chronically, it can contribute to various neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Therefore, research on the relationships between neurotoxicity and metal metabolism are being actively conducted, and some recent research has suggested that the mechanisms of metal-induced neurotoxicity critically involve endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Hence, this mini-review is to summarize some examples of such evidence and raise new questions in attempting to address metal-induced neurotoxicity with ER stress and mitochondria dysfunctions, two important topics for the effects of metals in neurodegenerative diseases. Taken together, to study the molecular programs of integrating ER stress with mitochondrial dysfunction should be an important area of future research for appreciating the mechanisms of as well as developing strategies and targets for metal-induced neurological diseases.
{"title":"Endoplasmic reticulum stress and mitochondrial dysfunctions in metal-induced neurological pathology","authors":"Sophia Cai, Min Woo Kim, Pan Chen","doi":"10.46439/neurobiology.4.020","DOIUrl":"https://doi.org/10.46439/neurobiology.4.020","url":null,"abstract":"Although essential metal ions are required in the body, neurotoxicity occurs when exposed to a concentration of metal that the body cannot accommodate. In the case of non-essential metals which are important in industry, these elements have the property of causing neurotoxicity even at small concentrations. When such neurotoxicity progresses chronically, it can contribute to various neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Therefore, research on the relationships between neurotoxicity and metal metabolism are being actively conducted, and some recent research has suggested that the mechanisms of metal-induced neurotoxicity critically involve endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Hence, this mini-review is to summarize some examples of such evidence and raise new questions in attempting to address metal-induced neurotoxicity with ER stress and mitochondria dysfunctions, two important topics for the effects of metals in neurodegenerative diseases. Taken together, to study the molecular programs of integrating ER stress with mitochondrial dysfunction should be an important area of future research for appreciating the mechanisms of as well as developing strategies and targets for metal-induced neurological diseases.","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":"4 1","pages":"4 - 8"},"PeriodicalIF":0.0,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46002647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commentary on \"Calcitonin-gene related peptide and neurologic injury: An emerging target for headache management\".","authors":"Phillip Johansen, Brandon Lucke-Wold","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":" ","pages":"20-22"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40491298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although essential metal ions are required in the body, neurotoxicity occurs when exposed to a concentration of metal that the body cannot accommodate. In the case of non-essential metals which are important in industry, these elements have the property of causing neurotoxicity even at small concentrations. When such neurotoxicity progresses chronically, it can contribute to various neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Therefore, research on the relationships between neurotoxicity and metal metabolism are being actively conducted, and some recent research has suggested that the mechanisms of metal-induced neurotoxicity critically involve endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Hence, this mini-review is to summarize some examples of such evidence and raise new questions in attempting to address metal-induced neurotoxicity with ER stress and mitochondria dysfunctions, two important topics for the effects of metals in neurodegenerative diseases. Taken together, to study the molecular programs of integrating ER stress with mitochondrial dysfunction should be an important area of future research for appreciating the mechanisms of as well as developing strategies and targets for metal-induced neurological diseases.
{"title":"Endoplasmic reticulum stress and mitochondrial dysfunctions in metal-induced neurological pathology.","authors":"Sophia Cai, Min Woo Kim, Pan Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although essential metal ions are required in the body, neurotoxicity occurs when exposed to a concentration of metal that the body cannot accommodate. In the case of non-essential metals which are important in industry, these elements have the property of causing neurotoxicity even at small concentrations. When such neurotoxicity progresses chronically, it can contribute to various neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Therefore, research on the relationships between neurotoxicity and metal metabolism are being actively conducted, and some recent research has suggested that the mechanisms of metal-induced neurotoxicity critically involve endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Hence, this mini-review is to summarize some examples of such evidence and raise new questions in attempting to address metal-induced neurotoxicity with ER stress and mitochondria dysfunctions, two important topics for the effects of metals in neurodegenerative diseases. Taken together, to study the molecular programs of integrating ER stress with mitochondrial dysfunction should be an important area of future research for appreciating the mechanisms of as well as developing strategies and targets for metal-induced neurological diseases.</p>","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":" ","pages":"4-8"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40715525","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}
Pub Date : 2022-01-01DOI: 10.46439/neurobiology.4.021
Michael Gurevitz, Boris S Zhorov, Ke Dong
Gating of voltage-dependent sodium channels involves coordinated movements of the voltage sensors in the voltage-sensing modules (VSMs) of the four domains (DI-DIV) in response to membrane depolarization. Zhu et al. have recently examined the effects of charge reversal substitutions at the VSM of domain III on the action of scorpion alpha- and beta-toxins that intercept the voltage sensors in domains IV and II, respectively. The increased activity of both toxin types on the mutant channels has suggested that the VSM module at domain III interacts allosterically with the VSM modules in domains IV and II during channel gating thus affecting indirectly the action of both scorpion toxin classes.
{"title":"Allosteric interactions among voltage-sensor modules of sodium channels probed by scorpion toxin modifiers.","authors":"Michael Gurevitz, Boris S Zhorov, Ke Dong","doi":"10.46439/neurobiology.4.021","DOIUrl":"https://doi.org/10.46439/neurobiology.4.021","url":null,"abstract":"<p><p>Gating of voltage-dependent sodium channels involves coordinated movements of the voltage sensors in the voltage-sensing modules (VSMs) of the four domains (DI-DIV) in response to membrane depolarization. Zhu et al. have recently examined the effects of charge reversal substitutions at the VSM of domain III on the action of scorpion alpha- and beta-toxins that intercept the voltage sensors in domains IV and II, respectively. The increased activity of both toxin types on the mutant channels has suggested that the VSM module at domain III interacts allosterically with the VSM modules in domains IV and II during channel gating thus affecting indirectly the action of both scorpion toxin classes.</p>","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":"4 1","pages":"9-12"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336684","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}
Pub Date : 2021-12-31DOI: 10.46439/neurobiology.3.016
{"title":"Surgical outcomes of the thoracic ossification of ligamentum flavum: A high incidence of combined spinal stenosis","authors":"","doi":"10.46439/neurobiology.3.016","DOIUrl":"https://doi.org/10.46439/neurobiology.3.016","url":null,"abstract":"","PeriodicalId":73855,"journal":{"name":"Journal of neurobiology and physiology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42533041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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