scholarly journals Alterations in Tau Protein Level and Phosphorylation State in the Brain of the Autistic-Like Rats Induced by Prenatal Exposure to Valproic Acid

2021 ◽  
Vol 22 (6) ◽  
pp. 3209
Author(s):  
Magdalena Gąssowska-Dobrowolska ◽  
Agnieszka Kolasa-Wołosiuk ◽  
Magdalena Cieślik ◽  
Agnieszka Dominiak ◽  
Kristina Friedland ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Cerebral Cortex ◽  
Synaptic Plasticity ◽  
Tau Protein ◽  
Dendritic Spine ◽  
Protein Level ◽  
Autism Spectrum ◽  
Spine Density ◽  
Phosphorylation State ◽  
Β Tubulin

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficient social interaction and communication besides repetitive, stereotyped behaviours. A characteristic feature of ASD is altered dendritic spine density and morphology associated with synaptic plasticity disturbances. Since microtubules (MTs) regulate dendritic spine morphology and play an important role in spine development and plasticity the aim of the present study was to investigate the alterations in the content of neuronal α/β-tubulin and Tau protein level as well as phosphorylation state in the valproic acid (VPA)-induced rat model of autism. Our results indicated that maternal exposure to VPA induces: (1) decrease the level of α/β-tubulin along with Tau accumulation in the hippocampus and cerebral cortex; (2) excessive Tau phosphorylation and activation of Tau-kinases: CDK5, ERK1/2, and p70S6K in the cerebral cortex; (3) up-regulation of mTOR kinase-dependent signalling in the hippocampus and cerebral cortex of adolescent rat offspring. Moreover, immunohistochemical staining showed histopathological changes in neurons (chromatolysis) in both analysed brain structures of rats prenatally exposed to VPA. The observed changes in Tau protein together with an excessive decrease in α/β-tubulin level may suggest destabilization and thus dysfunction of the MT cytoskeleton network, which in consequence may lead to the disturbance in synaptic plasticity and the development of autistic-like behaviours.

scholarly journals The Proliferation of Dentate Gyrus Progenitors in the Ferret Hippocampus by Neonatal Exposure to Valproic Acid

2021 ◽  
Vol 15 ◽  
Author(s):  
Kazuhiko Sawada ◽  
Shiori Kamiya ◽  
Ichio Aoki
Keyword(s):  
Valproic Acid ◽  
Cerebral Cortex ◽  
Magnetic Resonance ◽  
Dentate Gyrus ◽  
Structural Changes ◽  
S100 Protein ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Magnetic Resonance Images ◽  
Neonatal Exposure

Prenatal and neonatal exposure to valproic acid (VPA) is associated with human autism spectrum disorder (ASD) and can alter the development of several brain regions, such as the cerebral cortex, cerebellum, and amygdala. Neonatal VPA exposure induces ASD-like behavioral abnormalities in a gyrencephalic mammal, ferret, but it has not been evaluated in brain regions other than the cerebral cortex in this animal. This study aimed to facilitate a comprehensive understanding of brain abnormalities induced by developmental VPA exposure in ferrets. We examined gross structural changes in the hippocampus and tracked proliferative cells by 5-bromo-2-deoxyuridine (BrdU) labeling following VPA administration to ferret infants on postnatal days (PDs) 6 and 7 at 200 μg/g of body weight. Ex vivo short repetition time/time to echo magnetic resonance imaging (MRI) with high spatial resolution at 7-T was obtained from the fixed brain of PD 20 ferrets. The hippocampal volume estimated using MRI-based volumetry was not significantly different between the two groups of ferrets, and optical comparisons on coronal magnetic resonance images revealed no differences in gross structures of the hippocampus between VPA-treated and control ferrets. BrdU-labeled cells were observed throughout the hippocampus of both two groups at PD 20. BrdU-labeled cells were immunopositive for Sox2 (>70%) and almost immunonegative for NeuN, S100 protein, and glial fibrillary acidic protein. BrdU-labeled Sox2-positive progenitors were abundant, particularly in the subgranular layer of the dentate gyrus (DG), and were denser in VPA-treated ferrets. When BrdU-labeled Sox2-positive progenitors were examined at 2 h after the second VPA administration on PD 7, their density in the granular/subgranular layer and hilus of the DG was significantly greater in VPA-treated ferrets compared to controls. The findings suggest that VPA exposure to ferret infants facilitates the proliferation of DG progenitors, supplying excessive progenitors for hippocampal adult neurogenesis to the subgranular layer.

Rapid Effects of Estradiol on Dendritic Spines and Synaptic Plasticity in the Male and Female Hippocampus

2020 ◽  
pp. 38-47
Author(s):  
Asami Kato ◽  
Gen Murakami ◽  
Yasushi Hojo ◽  
Sigeo Horie ◽  
Suguru Kawato
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Hippocampal Slices ◽  
Spine Density ◽  
Male And Female ◽  
Dendritic Spine Density ◽  
Male And Female Rats ◽  
Rapid Modulation

Although the potent estrogen, 17β‎-estradiol (E2), has long been known to regulate the hippocampal dendritic spine density and synaptic plasticity, the molecular mechanisms through which it does so are less well understood. This chapter discusses the rapid modulation of hippocampal dendritic spine density and synaptic plasticity in male and female rats, with particular attention to studies in hippocampal slices from male rats. Among the mechanisms described are the roles of specific cell-signaling kinases and estrogen receptors in mediating the effects of E2 and progesterone on hippocampal neurons. In addition, dynamic changes of spine structures over time and sex differences in spine regulation are also considered. Finally, the chapter ends by discussing the importance of local hippocampal synthesis of E2 and androgens to hippocampal spine morphology and plasticity.

scholarly journals Close Homolog of L1 Regulates Dendritic Spine Density in the Mouse Cerebral Cortex Through Semaphorin 3B

2019 ◽  
Vol 39 (32) ◽  
pp. 6233-6250 ◽  
Author(s):  
Vishwa Mohan ◽  
Sarah D. Wade ◽  
Chelsea S. Sullivan ◽  
Michael R Kasten ◽  
Cassandra Sweetman ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Dendritic Spine ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Mouse Cerebral Cortex ◽  
Close Homolog

scholarly journals Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density

2011 ◽  
Vol 18 (9) ◽  
pp. 558-564 ◽  
Author(s):  
J. T. Rogers ◽  
I. Rusiana ◽  
J. Trotter ◽  
L. Zhao ◽  
E. Donaldson ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Ability ◽  
Dendritic Spine ◽  
Spine Density ◽  
Dendritic Spine Density

scholarly journals Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity

2013 ◽  
Vol 32 (12) ◽  
pp. 1730-1744 ◽  
Author(s):  
Elisabetta Menna ◽  
Stefania Zambetti ◽  
Raffaella Morini ◽  
Andrea Donzelli ◽  
Andrea Disanza ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spine ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Actin Capping

scholarly journals Age- and Sex-Specific Fear Conditioning Deficits in Mice Lacking Pcdh10, an Autism Associated Gene

2020 ◽  
Author(s):  
Sarah L. Ferri ◽  
Holly C. Dow ◽  
Hannah Schoch ◽  
Ji Youn Lee ◽  
Edward S. Brodkin ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Dendritic Spine ◽  
Basolateral Amygdala ◽  
Partial Agonist ◽  
Autism Spectrum ◽  
Contextual Fear Conditioning ◽  
Dark Phase ◽  
Spine Density ◽  
Social And Emotional ◽  
Male Specific

AbstractPCDH10 is a gene associated with Autism Spectrum Disorder. It is involved in the growth of thalamocortical projections and dendritic spine elimination. Previously, we characterized mice Pcdh10 haploinsufficient mice (Pcdh10+/− mice) and found male-specific social deficits that are rescued by N-methyl-D-aspartate receptor (NMDAR) partial agonist d-cycloserine, increased ultrasonic vocalizations in pups, and dark phase hypoactivity. In addition, we determined that the basolateral amygdala (BLA) of these mice exhibited increased dendritic spine density of immature morphology, decreased NMDAR expression, and decreased gamma synchronization. Here, we further characterize Pcdh10+/− mice by testing for fear memory, which relies upon BLA function. We used both male and female Pcdh10+/− mice and their wild-type littermates at two ages, juvenile and adult, and in two learning paradigms, cued and contextual fear conditioning. We found that males at both ages and in both assays exhibited fear conditioning deficits, but females were only impaired as adults in the cued condition. These data are further evidence for male-specific alterations in BLA-related behaviors in Pcdh10+/− mice, and suggest that these mice may be a useful model for dissecting male specific brain and behavioral phenotypes relevant to social and emotional behaviors.

scholarly journals Transcutaneous Electrical Acupoint Stimulation in Early Life Changes Synaptic Plasticity and Improves Symptoms in a Valproic Acid-Induced Rat Model of Autism

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xiaoxi Wang ◽  
Rui Ding ◽  
Yayue Song ◽  
Juan Wang ◽  
Chen Zhang ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Synaptic Plasticity ◽  
Rat Model ◽  
Early Life ◽  
Pain Threshold ◽  
Life Stage ◽  
Early Life Stage ◽  
Autism Spectrum ◽  
Therapeutic Effects ◽  
Acupoint Stimulation

Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficit in childhood without satisfactory medical intervention. Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive technique derived from acupuncture and has been shown to have similar therapeutic effects in many diseases. Valproic acid- (VPA-) induced ASD is a known model of ASD in rats. The therapeutic efficacy of TEAS was evaluated in the VPA model of ASD in the present study. The offspring of a VPA-treated rat received TEAS in the early life stage followed by a series of examinations conducted in their adolescence. The results show that following TEAS treatment in early life, the social and cognitive ability in adolescence of the offspring of a VPA rat were significantly improved. In addition, the abnormal pain threshold was significantly corrected. Additional studies demonstrated that the dendritic spine density of the primary sensory cortex was decreased with Golgi staining. Results of the transcriptomic study showed that expression of some transcription factors such as the neurotrophic factor were downregulated in the hypothalamus of the VPA model of ASD. The reduced gene expression was reversed following TEAS. These results suggest that TEAS in the early life stage may mitigate disorders of social and recognition ability and normalize the pain threshold of the ASD rat model. The mechanism involved may be related to improvement of synaptic plasticity.

scholarly journals MMP-9 Contributes to Dendritic Spine Remodeling Following Traumatic Brain Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Barbara Pijet ◽  
Marzena Stefaniuk ◽  
Leszek Kaczmarek
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebral Cortex ◽  
Brain Injury ◽  
Dendritic Spine ◽  
Contralateral Side ◽  
Spine Density ◽  
Morphological Transformation ◽  
Physical Trauma ◽  
Spine Shape ◽  
Wide Range

Traumatic brain injury (TBI) occurs when a blow to the head causes brain damage. Apart from physical trauma, it causes a wide range of cognitive, behavioral, and emotional deficits including impairments in learning and memory. On neuronal level, TBI may lead to circuitry remodeling and in effect imbalance between excitatory and inhibitory neurotransmissions. Such change in brain homeostasis may often lead to brain disorders. The basic units of neuronal connectivity are dendritic spines that are tiny protrusions forming synapses between two cells in a network. Spines are dynamic structures that undergo morphological transformation throughout life. Their shape is strictly related to an on/off state of synapse and the strength of synaptic transmission. Matrix metalloproteinase-9 (MMP-9) is an extrasynaptically operating enzyme that plays a role in spine remodeling and has been reported to be activated upon TBI. The aim of the present study was to evaluate the influence of MMP-9 on dendritic spine density and morphology following controlled cortical impact (CCI) as animal model of TBI. We examined spine density and dendritic spine shape in the cerebral cortex and the hippocampus. CCI caused a marked decrease in spine density as well as spine shrinkage in the cerebral cortex ipsilateral to the injury, when compared to sham animals and contralateral side both 1 day and 1 week after the insult. Decreased spine density was also observed in the dentate gyrus of the hippocampus; however, in contrast to the cerebral cortex, spines in the DG became more filopodia-like. In mice lacking MMP-9, no effects of TBI on spine density and morphology were observed.

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