Biomedicines

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2 pages, 176 KiB

Open AccessEditorial

Animal Models of Neurological Disorders: Where Are We Now?

by Sandesh Panthi and Marc Ekker

Biomedicines 2023, 11(5), 1253; https://doi.org/10.3390/biomedicines11051253 - 23 Apr 2023

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Abstract

The Special Issue “Animal Models of Neurological Disorders: Where Are We Now [...] Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

Research

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11 pages, 2099 KiB

Open AccessArticle

Multimodal Comparison of Diabetic Neuropathy in Aged Streptozotocin-Treated Sprague–Dawley and Zucker Diabetic Fatty Rats

by Annalisa Canta, Valentina A. Carozzi, Alessia Chiorazzi, Cristina Meregalli, Norberto Oggioni, Virginia Rodriguez-Menendez, Barbara Sala, Roberto Cosimo Melcangi, Silvia Giatti, Raffaella Lombardi, Roberto Bianchi, Paola Marmiroli and Guido Cavaletti

Biomedicines 2023, 11(1), 20; https://doi.org/10.3390/biomedicines11010020 - 22 Dec 2022

Cited by 1 | Viewed by 1216

Abstract

The development and progression of diabetic polyneuropathy (DPN) are due to multiple mechanisms. The creation of reliable animal models of DPN has been challenging and this issue has not yet been solved. However, despite some recognized differences from humans, most of the current [...] Read more.

The development and progression of diabetic polyneuropathy (DPN) are due to multiple mechanisms. The creation of reliable animal models of DPN has been challenging and this issue has not yet been solved. However, despite some recognized differences from humans, most of the current knowledge on the pathogenesis of DPN relies on results achieved using rodent animal models. The simplest experimental DPN model reproduces type 1 diabetes, induced by massive chemical destruction of pancreatic beta cells with streptozotocin (STZ). Spontaneous/transgenic models of diabetes are less frequently used, mostly because they are less predictable in clinical course, more expensive, and require a variable time to achieve homogeneous metabolic conditions. Among them, Zucker diabetic fatty (ZDF) rats represent a typical type 2 diabetes model. Both STZ-induced and ZDF rats have been extensively used, but only very few studies have compared the long-term similarities and differences existing between these two models. Moreover, inconsistencies have been reported regarding several aspects of short-term in vivo studies using these models. In this study, we compared the long-term course of DPN in STZ-treated Sprague–Dawley and ZDF rats with a multimodal set of readout measures. Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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15 pages, 1653 KiB

Open AccessArticle

A Missense Variant in PDK1 Associated with Severe Neurodevelopmental Delay and Epilepsy

by Raquel Vaz, Josephine Wincent, Najla Elfissi, Kristina Rosengren Forsblad, Maria Pettersson, Karin Naess, Anna Wedell, Anna Wredenberg, Anna Lindstrand and Sofia Ygberg

Biomedicines 2022, 10(12), 3171; https://doi.org/10.3390/biomedicines10123171 - 07 Dec 2022

Cited by 1 | Viewed by 1742

Abstract

The pyruvate dehydrogenase complex (PDC) is responsible for the conversion of pyruvate into acetyl-CoA, which is used for energy conversion in cells. PDC activity is regulated by phosphorylation via kinases and phosphatases (PDK/PDP). Variants in all subunits of the PDC and in PDK3 [...] Read more.

The pyruvate dehydrogenase complex (PDC) is responsible for the conversion of pyruvate into acetyl-CoA, which is used for energy conversion in cells. PDC activity is regulated by phosphorylation via kinases and phosphatases (PDK/PDP). Variants in all subunits of the PDC and in PDK3 have been reported, with varying phenotypes including lactic acidosis, neurodevelopmental delay, peripheral neuropathy, or seizures. Here, we report a de novo heterozygous missense variant in PDK1 (c.1139G > A; p.G380D) in a girl with developmental delay and early onset severe epilepsy. To investigate the role of PDK1^G380D in energy metabolism and neuronal development, we used a zebrafish model. In zebrafish embryos we show a reduced number of cells with mitochondria with membrane potential, reduced movements, and a delay in neuronal development. Furthermore, we observe a reduction in the phosphorylation of PDH-E1α by PDK^G380D, which suggests a disruption in the regulation of PDC activity. Finally, in patient fibroblasts, a mild reduction in the ratio of phosphorylated PDH over total PDH-E1α was detected. In summary, our findings support the notion that this aberrant PDK1 activity is the cause of clinical symptoms in the patient. Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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12 pages, 1775 KiB

Open AccessArticle

Effect of Fluoxetine and Acacetin on Central Vestibular Compensation in an Animal Model of Unilateral Peripheral Vestibulopathy

by Bérénice Hatat, Romain Boularand, Claire Bringuier, Nicolas Chanut, Christian Chabbert and Brahim Tighilet

Biomedicines 2022, 10(9), 2097; https://doi.org/10.3390/biomedicines10092097 - 27 Aug 2022

Cited by 2 | Viewed by 1326

Abstract

Damage to the peripheral vestibular system is known to generate a syndrome characterized by postural, locomotor, oculomotor, perceptual and cognitive deficits. Current pharmacological therapeutic solutions for these pathologies lack specificity and efficacy. Recently, we demonstrated that apamin, a specific SK channel blocker, significantly [...] Read more.

Damage to the peripheral vestibular system is known to generate a syndrome characterized by postural, locomotor, oculomotor, perceptual and cognitive deficits. Current pharmacological therapeutic solutions for these pathologies lack specificity and efficacy. Recently, we demonstrated that apamin, a specific SK channel blocker, significantly reduced posturo-locomotor and oculomotor deficits in the cat and the rat. The aim of the present study was to test the antivertigo potential of compounds belonging to the SK antagonists family, such as Acacetin and Fluoxetine. Young rats were subjected to unilateral ototoxic lesions of the vestibular organ using transtympanic administration of arsanilic acid (TTA) to evoke unilateral vestibular loss (UVL). Vestibular syndrome was monitored using behavioural evaluation allowing appreciation of the evolution of static and dynamic posturo-locomotor deficits. A significant effect of the TTA insult was only found on the distance moved, the mean body velocity and the not moving time. From day 2 to week 2 after TTA, the distance moved and the mean body velocity were significantly decreased, while the not moving time was significantly increased. Acacetin does not evoke any significant change in the vestibular posturo-locomotor parameters’ kinetics. Administration of Fluoxetine two weeks before TTA and over three weeks after TTA (preventive group) does not evoke any significant change in the vestibular posturo-locomotor parameters’ kinetics. Administration of Fluoxetine from three weeks after TTA significantly delayed the functional recovery. This study demonstrates that Acacetin or Fluoxetine in TTA vestibulo-injured rats does not bring any significant benefit on the posture and locomotor balance deficits. Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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20 pages, 11475 KiB

Open AccessArticle

A nop56 Zebrafish Loss-of-Function Model Exhibits a Severe Neurodegenerative Phenotype

by Ana Quelle-Regaldie, Mónica Folgueira, Julián Yáñez, Daniel Sobrido-Cameán, Anabel Alba-González, Antón Barreiro-Iglesias, María-Jesús Sobrido and Laura Sánchez

Biomedicines 2022, 10(8), 1814; https://doi.org/10.3390/biomedicines10081814 - 28 Jul 2022

Cited by 5 | Viewed by 2101

Abstract

NOP56 belongs to a C/D box small nucleolar ribonucleoprotein complex that is in charge of cleavage and modification of precursor ribosomal RNAs and assembly of the 60S ribosomal subunit. An intronic expansion in NOP56 gene causes Spinocerebellar Ataxia type 36, a typical late-onset [...] Read more.

NOP56 belongs to a C/D box small nucleolar ribonucleoprotein complex that is in charge of cleavage and modification of precursor ribosomal RNAs and assembly of the 60S ribosomal subunit. An intronic expansion in NOP56 gene causes Spinocerebellar Ataxia type 36, a typical late-onset autosomal dominant ataxia. Although vertebrate animal models were created for the intronic expansion, none was studied for the loss of function of NOP56. We studied a zebrafish loss-of-function model of the nop56 gene which shows 70% homology with the human gene. We observed a severe neurodegenerative phenotype in nop56 mutants, characterized mainly by absence of cerebellum, reduced numbers of spinal cord neurons, high levels of apoptosis in the central nervous system (CNS) and impaired movement, resulting in death before 7 days post-fertilization. Gene expression of genes related to C/D box complex, balance and CNS development was impaired in nop56 mutants. In our study, we characterized the first NOP56 loss-of-function vertebrate model, which is important to further understand the role of NOP56 in CNS function and development. Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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Review

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17 pages, 2197 KiB

Open AccessReview

What Predictability for Animal Models of Peripheral Vestibular Disorders?

by Brahim Tighilet, Jessica Trico, Frédéric Xavier and Christian Chabbert

Biomedicines 2022, 10(12), 3097; https://doi.org/10.3390/biomedicines10123097 - 01 Dec 2022

Cited by 2 | Viewed by 1641

Abstract

The different clinical entities grouped under the term peripheral vestibulopathies (PVs) or peripheral vestibular disorders (PVDs) are distinguished mainly based on their symptoms/clinical expression. Today, there are very few commonly accepted functional and biological biomarkers that can confirm or refute whether a vestibular [...] Read more.

The different clinical entities grouped under the term peripheral vestibulopathies (PVs) or peripheral vestibular disorders (PVDs) are distinguished mainly based on their symptoms/clinical expression. Today, there are very few commonly accepted functional and biological biomarkers that can confirm or refute whether a vestibular disorder belongs to a precise classification. Consequently, there is currently a severe lack of reliable and commonly accepted clinical endpoints, either to precisely follow the course of the vertigo syndrome of vestibular origin or to assess the benefits of therapeutic approaches, whether they are pharmacological or re-educational. Animal models of PV are a good means to identify biomarkers that could subsequently be exploited in human clinical practice. The question of their predictability is therefore crucial. Ten years ago, we had already raised this question. We revisit this concept today in order to take into account the animal models of peripheral vestibular pathology that have emerged over the last decade, and the new technological approaches available for the behavioral assessment of vestibular syndrome in animals and its progression over time. The questions we address in this review are the following: are animal models of PV predictive of the different types and stages of vestibular pathologies, and if so, to what extent? Are the benefits of the pharmacological or reeducational therapeutic approaches achieved on these different models of PV (in particular the effects of attenuation of the acute vertigo, or acceleration of central compensation) predictive of those expected in the vertiginous patient, and if so, to what extent? Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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33 pages, 1039 KiB

Open AccessReview

Rodent Models of Audiogenic Epilepsy: Genetic Aspects, Advantages, Current Problems and Perspectives

by David G. Garbuz, Artem A. Davletshin, Svetlana A. Litvinova, Irina B. Fedotova, Natalya M. Surina and Inga I. Poletaeva

Biomedicines 2022, 10(11), 2934; https://doi.org/10.3390/biomedicines10112934 - 15 Nov 2022

Cited by 9 | Viewed by 1984

Abstract

Animal models of epilepsy are of great importance in epileptology. They are used to study the mechanisms of epileptogenesis, and search for new genes and regulatory pathways involved in the development of epilepsy as well as screening new antiepileptic drugs. Today, many methods [...] Read more.

Animal models of epilepsy are of great importance in epileptology. They are used to study the mechanisms of epileptogenesis, and search for new genes and regulatory pathways involved in the development of epilepsy as well as screening new antiepileptic drugs. Today, many methods of modeling epilepsy in animals are used, including electroconvulsive, pharmacological in intact animals, and genetic, with the predisposition for spontaneous or refractory epileptic seizures. Due to the simplicity of manipulation and universality, genetic models of audiogenic epilepsy in rodents stand out among this diversity. We tried to combine data on the genetics of audiogenic epilepsy in rodents, the relevance of various models of audiogenic epilepsy to certain epileptic syndromes in humans, and the advantages of using of rodent strains predisposed to audiogenic epilepsy in current epileptology. Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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25 pages, 2541 KiB

Open AccessReview

Electric Fields Induced in the Brain by Transcranial Electric Stimulation: A Review of In Vivo Recordings

by Matteo Guidetti, Mattia Arlotti, Tommaso Bocci, Anna Maria Bianchi, Marta Parazzini, Roberta Ferrucci and Alberto Priori

Biomedicines 2022, 10(10), 2333; https://doi.org/10.3390/biomedicines10102333 - 20 Sep 2022

Cited by 11 | Viewed by 3564

Abstract

Transcranial electrical stimulation (tES) techniques, such as direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), cause neurophysiological and behavioral modifications as responses to the electric field are induced in the brain. Estimations of such electric fields are based mainly on computational [...] Read more.

Transcranial electrical stimulation (tES) techniques, such as direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), cause neurophysiological and behavioral modifications as responses to the electric field are induced in the brain. Estimations of such electric fields are based mainly on computational studies, and in vivo measurements have been used to expand the current knowledge. Here, we review the current tDCS- and tACS-induced electric fields estimations as they are recorded in humans and non-human primates using intracerebral electrodes. Direct currents and alternating currents were applied with heterogeneous protocols, and the recording procedures were characterized by a tentative methodology. However, for the clinical stimulation protocols, an injected current seems to reach the brain, even at deep structures. The stimulation parameters (e.g., intensity, frequency and phase), the electrodes’ positions and personal anatomy determine whether the intensities might be high enough to affect both neuronal and non-neuronal cell activity, also deep brain structures. Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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Other

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32 pages, 3044 KiB

Open AccessSystematic Review

How Well Do Rodent Models of Parkinson’s Disease Recapitulate Early Non-Motor Phenotypes? A Systematic Review

by Tracy D. Zhang, Scott C. Kolbe, Leah C. Beauchamp, Ella K. Woodbridge, David I. Finkelstein and Emma L. Burrows

Biomedicines 2022, 10(12), 3026; https://doi.org/10.3390/biomedicines10123026 - 24 Nov 2022

Cited by 5 | Viewed by 2595

Abstract

The prodromal phase of Parkinson’s disease (PD) is characterised by many non-motor symptoms, and these have recently been posited to be predictive of later diagnosis. Genetic rodent models can develop non-motor phenotypes, providing tools to identify mechanisms underlying the early development of PD. [...] Read more.

The prodromal phase of Parkinson’s disease (PD) is characterised by many non-motor symptoms, and these have recently been posited to be predictive of later diagnosis. Genetic rodent models can develop non-motor phenotypes, providing tools to identify mechanisms underlying the early development of PD. However, it is not yet clear how reproducible non-motor phenotypes are amongst genetic PD rodent models, whether phenotypes are age-dependent, and the translatability of these phenotypes has yet to be explored. A systematic literature search was conducted on studies using genetic PD rodent models to investigate non-motor phenotypes; cognition, anxiety/depressive-like behaviour, gastrointestinal (GI) function, olfaction, circadian rhythm, cardiovascular and urinary function. In total, 51 genetic models of PD across 150 studies were identified. We found outcomes of most phenotypes were inconclusive due to inadequate studies, assessment at different ages, or variation in experimental and environmental factors. GI dysfunction was the most reproducible phenotype across all genetic rodent models. The mouse model harbouring mutant A53T, and the wild-type hα-syn overexpression (OE) model recapitulated the majority of phenotypes, albeit did not reliably produce concurrent motor deficits and nigral cell loss. Furthermore, animal models displayed different phenotypic profiles, reflecting the distinct genetic risk factors and heterogeneity of disease mechanisms. Currently, the inconsistent phenotypes within rodent models pose a challenge in the translatability and usefulness for further biomechanistic investigations. This review highlights opportunities to improve phenotype reproducibility with an emphasis on phenotypic assay choice and robust experimental design. Full article

(This article belongs to the Special Issue Animal Models of Neurological Disorders: Where Are We Now?)

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