Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases

Lenahan, Cameron; Sanghavi, Rajvee; Huang, Lei; Zhang, Junyi

doi:10.3389/fnins.2020.00326

Cited by 26 publications

(22 citation statements)

References 85 publications

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“…This balance is crucial for optimal neural signal formation and transmission, and several theories suggest that an increased in this balance might underlie the abnormalities encountered in ASD [ 90 – 92 ]. In the occipital cortex, the absence of group difference in GABA + or Glx concentrations is in line with the literature (GABA + : [ 49 , 52 , 55 , 56 ]; Glx: [ 49 , 52 ]).…”

Section: Discussionsupporting

confidence: 91%

“…To the best of our knowledge, this study is the first one to quantify these metabolite concentrations in the right IFG of autistic adults. A few studies measured them in other frontal regions in the left hemisphere in autistic adults, and showed no difference in GABA + (left ventral premotor cortex, [ 56 ]) nor Glx (left dorsolateral prefrontal cortex, [ 46 , 50 ]). In autistic children, glutamate was found to be increased in a frontal region (unspecified MRS voxel localization) and this measurement was strongly positively correlated with blood glutamate levels [ 89 ].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding GABA, most of the evidence is in favour of a decreased action of GABA in ASD [ 37 , 54 ]. In autistic adults, MRS studies mostly found decreased GABA levels (sensorimotor cortex [ 55 ], supplementary motor area [ 56 ], ACC [ 43 ], cerebellum [ 43 ]) or no group differences (frontal regions [ 47 , 49 , 51 , 52 , 56 , 57 ], occipital regions [ 49 , 52 , 55 , 56 ], auditory cortex [ 52 , 58 ], ACC [ 59 ], striatum [ 47 ]).…”

Section: Introductionmentioning

confidence: 99%

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Prediction learning in adults with autism and its molecular correlates

et al. 2021

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Background According to Bayesian hypotheses, individuals with Autism Spectrum Disorder (ASD) have difficulties making accurate predictions about their environment. In particular, the mechanisms by which they assign precision to predictions or sensory inputs would be suboptimal in ASD. These mechanisms are thought to be mostly mediated by glutamate and GABA. Here, we aimed to shed light on prediction learning in ASD and on its neurobiological correlates. Methods Twenty-six neurotypical and 26 autistic adults participated in an associative learning task where they had to learn a probabilistic association between a tone and the rotation direction of two dots, in a volatile context. They also took part in magnetic resonance spectroscopy (MRS) measurements to quantify Glx (glutamate and glutamine), GABA + and glutathione in a low-level perceptual region (occipital cortex) and in a higher-level region involved in prediction learning (inferior frontal gyrus). Results Neurotypical and autistic adults had their percepts biased by their expectations, and this bias was smaller for individuals with a more atypical sensory sensitivity. Both groups were able to learn the association and to update their beliefs after a change in contingency. Interestingly, the percentage of correct predictions was correlated with the Glx/GABA + ratio in the occipital cortex (positive correlation) and in the right inferior frontal gyrus (negative correlation). In this region, MRS results also showed an increased concentration of Glx in the ASD group compared to the neurotypical group. Limitations We used a quite restrictive approach to select the MR spectra showing a good fit, which led to the exclusion of some MRS datasets and therefore to the reduction of the sample size for certain metabolites/regions. Conclusions Autistic adults appeared to have intact abilities to make predictions in this task, in contrast with the Bayesian hypotheses of ASD. Yet, higher ratios of Glx/GABA + in a frontal region were associated with decreased predictive abilities, and ASD individuals tended to have more Glx in this region. This neurobiological difference might contribute to suboptimal predictive mechanisms in ASD in certain contexts.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prediction learning in adults with autism and its molecular correlates

et al. 2021

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“…As previously described, KO of rhodopsin abolished rod-driven electrophysical activity ( Xiao et al, 2019 ). Moreover, a connection between altered rhodopsin levels and neurodegenerative processes as well as the use of rhodopsin as a potential early biomarker have been reviewed previously by Lenahan et al (2020) . In contrast, although Rho mRNA levels were also observed significantly lower, an unaltered rhodopsin immunoreactivity was found in ischemic rat models ( Zhao et al, 2013 ; Palmhof et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Knock-Out of Tenascin-C Ameliorates Ischemia-Induced Rod-Photoreceptor Degeneration and Retinal Dysfunction

et al. 2021

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Retinal ischemia is a common pathomechanism in various eye diseases. Recently, evidence accumulated suggesting that the extracellular matrix (ECM) glycoprotein tenascin-C (Tnc) plays a key role in ischemic degeneration. However, the possible functional role of Tnc in retinal ischemia is not yet known. The aim of our study was to explore retinal function and rod-bipolar/photoreceptor cell degeneration in wild type (WT) and Tnc knock-out (KO) mice after ischemia/reperfusion (I/R) injury. Therefore, I/R was induced by increasing intraocular pressure in the right eye of wild type (WT I/R) and Tnc KO (KO I/R) mice. The left eye served as untreated control (WT CO and KO CO). Scotopic electroretinogram (ERG) recordings were performed to examine rod-bipolar and rod-photoreceptor cell function. Changes of Tnc, rod-bipolar cells, photoreceptors, retinal structure and apoptotic and synaptic alterations were analyzed by immunohistochemistry, Hematoxylin and Eosin staining, Western blot, and quantitative real time PCR. We found increased Tnc protein levels 3 days after ischemia, while Tnc immunoreactivity decreased after 7 days. Tnc mRNA expression was comparable in the ischemic retina. ERG measurements after 7 days showed lower a-/b-wave amplitudes in both ischemic groups. Nevertheless, the amplitudes in the KO I/R group were higher than in the WT I/R group. We observed retinal thinning in WT I/R mice after 3 and 7 days. Although compared to the KO CO group, retinal thinning was not observed in the KO I/R group until 7 days. The number of PKCα+ rod-bipolar cells, recoverin+ photoreceptor staining and Prkca and Rcvrn expression were comparable in all groups. However, reduced rhodopsin protein as well as Rho and Gnat1 mRNA expression levels of rod-photoreceptors were found in the WT I/R, but not in the KO I/R retina. Additionally, a lower number of activated caspase 3+ cells was observed in the KO I/R group. Finally, both ischemic groups displayed enhanced vesicular glutamate transporter 1 (vGlut1) levels. Collectively, KO mice showed diminished rod-photoreceptor degeneration and retinal dysfunction after I/R. Elevated vGlut1 levels after ischemia could be related to an impaired glutamatergic photoreceptor-bipolar cell signaling and excitotoxicity. Our study provides novel evidence that Tnc reinforces ischemic retinal degeneration, possibly by synaptic remodeling.

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“…Optogenetics (i.e., a combination of “optics” and “genetics”) uses mainly genetically encoded, and often specifically engineered, microbial rhodopsins for the optical control of physiological processes [ 7 – 10 , 16 , 41 ]. The development of so-called optogenetic tools leads to the investigation of the nervous system at the cellular and tissue level, without noticeable tissue damage as well as side effects.…”

Section: Rhodopsins: a Family Of Biological Photoreceptorsmentioning

confidence: 99%

Evolution of the Automatic Rhodopsin Modeling (ARM) Protocol

et al. 2022

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In recent years, photoactive proteins such as rhodopsins have become a common target for cutting-edge research in the field of optogenetics. Alongside wet-lab research, computational methods are also developing rapidly to provide the necessary tools to analyze and rationalize experimental results and, most of all, drive the design of novel systems. The Automatic Rhodopsin Modeling (ARM) protocol is focused on providing exactly the necessary computational tools to study rhodopsins, those being either natural or resulting from mutations. The code has evolved along the years to finally provide results that are reproducible by any user, accurate and reliable so as to replicate experimental trends. Furthermore, the code is efficient in terms of necessary computing resources and time, and scalable in terms of both number of concurrent calculations as well as features. In this review, we will show how the code underlying ARM achieved each of these properties.

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Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases

Cited by 26 publications

References 85 publications

Prediction learning in adults with autism and its molecular correlates

Prediction learning in adults with autism and its molecular correlates

Knock-Out of Tenascin-C Ameliorates Ischemia-Induced Rod-Photoreceptor Degeneration and Retinal Dysfunction

Evolution of the Automatic Rhodopsin Modeling (ARM) Protocol

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