scholarly journals A Composite Sketch of Fast-Spiking Parvalbumin-Positive Neurons

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Odile Bartholome ◽  
Orianne de la Brassinne Bonardeaux ◽  
Virginie Neirinckx ◽  
Bernard Rogister
Keyword(s):  
Current Knowledge ◽  
Neuronal Population ◽  
Inhibitory Neurons ◽  
Potential Contribution ◽  
Pathological Conditions ◽  
Fast Spiking ◽  
Chandelier Cells ◽  
And Migration ◽  
A Minor ◽  
The Brain

Abstract Parvalbumin-positive neurons are inhibitory neurons that release GABA and are mostly represented by fast-spiking basket or chandelier cells. They constitute a minor neuronal population, yet their peculiar profiles allow them to react quickly to any event in the brain under normal or pathological conditions. In this review, we will summarize the current knowledge about the fundamentals of fast-spiking parvalbumin-positive neurons, focusing on their morphology and specific channel/protein content. Next, we will explore their development, maturation, and migration in the brain. Finally, we will unravel their potential contribution to the physiopathology of epilepsy.

scholarly journals Sharp tuning of head direction by somatosensory fast-spiking interneurons

2020 ◽  
Author(s):  
Xiaoyang Long ◽  
Calvin K. Young ◽  
Sheng-Jia Zhang
Keyword(s):  
Cell Types ◽  
Inhibitory Neurons ◽  
Local Network ◽  
Head Direction ◽  
Layer 4 ◽  
Fast Spiking ◽  
External Stimuli ◽  
The Brain ◽  
Spatial Cell

AbstractHead direction (HD) information is intricately linked to spatial navigation and cognition. We recently reported the co-existence of all currently recognized spatial cell types can be found in the hindlimb primary somatosensory cortex (S1HL). In this study, we carried out an in-depth characterization of HD cells in S1HL. We show fast-spiking (FS), putative inhibitory neurons are over-represented in and sharply tuned to HD compared to regular-spiking (RS), putative excitatory neurons. These FS HD cells are non-conjunctive, rarely theta modulated, not locally connected and are enriched in layer 4/5a. Their co-existence with RS HD cells and angular head velocity (AHV) cells in a layer-specific fashion through the S1HL presents a previously unreported organization of spatial circuits. These findings challenge the notion that FS, putative inhibitory interneurons are weakly tuned to external stimuli in general and present a novel local network configuration not reported in other parts of the brain.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Experimental Rodent Models of Vascular Dementia: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nidhi Tiwari ◽  
Jyoti Upadhyay ◽  
Mohd Nazam Ansari ◽  
Syed Shadab Raza ◽  
Wasim Ahmad ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Current Knowledge ◽  
Vascular Cognitive Impairment ◽  
Experimental Models ◽  
New Drugs ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
The Brain ◽  
Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

scholarly journals L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 682
Author(s):  
Matthias Christen ◽  
Nils Janzen ◽  
Anne Fraser ◽  
Adrian C. Sewell ◽  
Vidhya Jagannathan ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Genetic Defect ◽  
Clinical Signs ◽  
Missense Variant ◽  
Microcytic Anemia ◽  
Abnormal Behavior ◽  
Functional Candidate Gene ◽  
History Of ◽  
The Brain ◽  
Hydroxyglutaric Acid

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.

scholarly journals The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

scholarly journals Human Monocytes Plasticity in Neurodegeneration

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 717
Author(s):  
Ilenia Savinetti ◽  
Angela Papagna ◽  
Maria Foti
Keyword(s):  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Surface Marker ◽  
First Line ◽  
Surface Marker Expression ◽  
Physiological Properties ◽  
Attractive Therapeutic Target ◽  
The Brain ◽  
Lateral Sclerosis

Monocytes play a crucial role in immunity and tissue homeostasis. They constitute the first line of defense during the inflammatory process, playing a role in the pathogenesis and progression of diseases, making them an attractive therapeutic target. They are heterogeneous in morphology and surface marker expression, which suggest different molecular and physiological properties. Recent evidences have demonstrated their ability to enter the brain, and, as a consequence, their hypothetical role in different neurodegenerative diseases. In this review, we will discuss the current knowledge about the correlation between monocyte dysregulation in the brain and/or in the periphery and neurological diseases in humans. Here we will focus on the most common neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis.

scholarly journals Tcf4 Is Involved in Subset Specification of Mesodiencephalic Dopaminergic Neurons

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 317
Author(s):  
Simone Mesman ◽  
Iris Wever ◽  
Marten P. Smidt
Keyword(s):  
Neuronal Differentiation ◽  
Dopaminergic Neurons ◽  
Neuronal Development ◽  
Neuronal Population ◽  
Minor Role ◽  
Initial Increase ◽  
E Box ◽  
A Minor ◽  
Bhlh Factor

During development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of Tcf4, a member of the E-box protein family, in mdDA neuronal development and subset specification. We show that Tcf4 is expressed throughout development, but is no longer detected in adult midbrain. Deletion of Tcf4 results in an initial increase in TH-expressing neurons at E11.5, but this normalizes at later embryonic stages. However, the caudal subset marker Nxph3 and rostral subset marker Ahd2 are affected at E14.5, indicating that Tcf4 is involved in correct differentiation of mdDA neuronal subsets. At P0, expression of these markers partially recovers, whereas expression of Th transcript and TH protein appears to be affected in lateral parts of the mdDA neuronal population. The initial increase in TH-expressing cells and delay in subset specification could be due to the increase in expression of the bHLH factor Ascl1, known for its role in mdDA neuronal differentiation, upon loss of Tcf4. Taken together, our data identified a minor role for Tcf4 in mdDA neuronal development and subset specification.

scholarly journals Tissue-specific distribution of cross-linked somatostatin receptor proteins in the rat

1992 ◽  
Vol 282 (2) ◽  
pp. 339-344 ◽  
Author(s):  
C B Srikant ◽  
K K Murthy ◽  
Y C Patel
Keyword(s):  
Exocrine Pancreas ◽  
Receptor Protein ◽  
Cross Linking ◽  
Molecular Heterogeneity ◽  
Dependent Manner ◽  
Tissue Specific ◽  
Receptor Proteins ◽  
Specific Distribution ◽  
A Minor ◽  
The Brain

Pharmacological studies have suggested that the somatostatin (SS) receptor is heterogeneous and exhibits SS-14-and SS-28-selective subtypes. Whether such subtypes arise from molecular heterogeneity of the receptor protein has not been definitively established. Previous reports characterizing the molecular properties of the SS receptor by the cross-linking approach have yielded divergent size estimates ranging from 27 kDa to 200 kDa. In order to resolve this discrepancy, as well as to determine whether SS-14 and SS-28 interact with specific receptor proteins, we have cross-linked radioiodinated derivatives of [125I-Tyr11]SS-14 (T*-SS-14) and [Leu8,D-Trp22,125I-Tyr25]SS-28 (LTT*-SS-28) to membrane SS receptors in rat brain, pituitary, exocrine pancreas and adrenal cortex using a number of chemical and photoaffinity cross-linking agents. The labelled cross-linked receptor proteins were analysed by SDS/PAGE under reducing conditions followed by autoradiography. Our findings indicate that the pattern of specifically labelled cross-linked SS receptor proteins is sensitive to the concentration of chemical cross-linking agents such as disuccinimidyl suberate and dithiobis-(succinimidyl propionate). Labelled high-molecular-mass complexes of cross-linked receptor-ligand proteins were observed only when high concentrations of these cross-linkers were employed. Using optimized low concentrations of cross-linkers, however, two major labelled bands of 58 +/- 3 kDa and 27 +/- 2 kDa were detected. These two bands were identified as specifically labelled SS receptor proteins subsequent to cross-linking with a number of photoaffinity cross-linking agents as well. We demonstrate here that the 58 kDa protein is the major SS receptor protein in the rat pituitary, adrenal and exocrine pancreas, whereas the 27 kDa moiety represents the principal form in the brain. Additionally, the presence of a minor specifically labelled band of 32 kDa was detected uniquely in the brain, and a minor labelled protein of 42 kDa was observed in the pancreas. The labelling pattern obtained with LTT*-SS-28 was identical to that observed with T*-SS-14. Labelling of the 27 kDa band by either ligand was inhibited by SS-14 and SS-28 in a dose-dependent manner. Densitometric quantification showed that SS-14 exhibited greater than 2-fold greater potency than SS-28 for inhibiting the labelling of the 27 kDa species. These findings emphasize the need for careful interpretation of cross-linking data obtained for SS receptors, and provide evidence for molecular heterogeneity and for a tissue-specific distribution of the two principal SS receptor proteins.

Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain

2021 ◽  
Author(s):  
Shachar Sherman ◽  
Koichi Kawakami ◽  
Herwig Baier
Keyword(s):  
Visual Information ◽  
Visual Stimulation ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Vertebrate Brain ◽  
Relative Contribution ◽  
Retinal Input ◽  
And Migration ◽  
The Brain

The brain is assembled during development by both innate and experience-dependent mechanisms1-7, but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components7-9. Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs10 and central neurons11-16. Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog17 and gene expression atlas18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz (atoh7-) mutants, in which RGCs do not form19. Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.

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