scholarly journals Synaptic Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders

2021 ◽  
Vol 22 (18) ◽  
pp. 10058
Author(s):  
Grzegorz A. Czapski ◽  
Lidia Babiec ◽  
Henryk Jęśko ◽  
Magdalena Gąssowska-Dobrowolska ◽  
Magdalena Cieślik ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Memory Function ◽  
Autism Spectrum ◽  
Synaptic Proteins ◽  
Object Recognition Test ◽  
Transgenic Model ◽  
Transmission Electron ◽  
Mental Symptoms ◽  
Synaptic Pathology

Tuberous sclerosis complex (TSC) is a rare, multi-system genetic disease with serious neurological and mental symptoms, including autism. Mutations in the TSC1/TSC2 genes lead to the overactivation of mTOR signalling, which is also linked to nonsyndromic autism. Our aim was to analyse synaptic pathology in a transgenic model of TSC: two-month-old male B6;129S4-Tsc2tm1Djk/J mice with Tsc2 haploinsufficiency. Significant brain-region-dependent alterations in the expression of several synaptic proteins were identified. The most prominent changes were observed in the immunoreactivity of presynaptic VAMP1/2 (ca. 50% increase) and phospho-synapsin-1 (Ser62/67) (ca. 80% increase). Transmission electron microscopy demonstrated serious ultrastructural abnormalities in synapses such as a blurred structure of synaptic density and a significantly increased number of synaptic vesicles. The impairment of synaptic mitochondrial ultrastructure was represented by excessive elongation, swelling, and blurred crista contours. Polyribosomes in the cytoplasm and swollen Golgi apparatus suggest possible impairment of protein metabolism. Moreover, the delamination of myelin and the presence of vacuolar structures in the cell nucleus were observed. We also report that Tsc2+/− mice displayed increased brain weights and sizes. The behavioural analysis demonstrated the impairment of memory function, as established in the novel object recognition test. To summarise, our data indicate serious synaptic impairment in the brains of male Tsc2+/− mice.

scholarly journals The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex

2019 ◽  
Vol 30 (4) ◽  
pp. 2199-2214
Author(s):  
Benoit Scherrer ◽  
Anna K Prohl ◽  
Maxime Taquet ◽  
Kush Kapur ◽  
Jurriaan M Peters ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Face Processing ◽  
Genetic Disorder ◽  
Neuropsychiatric Symptoms ◽  
Autism Spectrum ◽  
The Body ◽  
Fusiform Gyrus ◽  
Benign Tumors ◽  
Anatomical Connectivity

Abstract Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors throughout the body; it is generally diagnosed early in life and has a high prevalence of autism spectrum disorder (ASD), making it uniquely valuable in studying the early development of autism, before neuropsychiatric symptoms become apparent. One well-documented deficit in ASD is an impairment in face processing. In this work, we assessed whether anatomical connectivity patterns of the fusiform gyrus, a central structure in face processing, capture the risk of developing autism early in life. We longitudinally imaged TSC patients at 1, 2, and 3 years of age with diffusion compartment imaging. We evaluated whether the anatomical connectivity fingerprint of the fusiform gyrus was associated with the risk of developing autism measured by the Autism Observation Scale for Infants (AOSI). Our findings suggest that the fusiform gyrus connectivity captures the risk of developing autism as early as 1 year of age and provides evidence that abnormal fusiform gyrus connectivity increases with age. Moreover, the identified connections that best capture the risk of developing autism involved the fusiform gyrus and limbic and paralimbic regions that were consistent with the ASD phenotype, involving an increased number of left-lateralized structures with increasing age.

scholarly journals Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna K. Prohl ◽  
◽  
Benoit Scherrer ◽  
Xavier Tomas-Fernandez ◽  
Peter E. Davis ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
White Matter ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Neural Circuits ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Fiber Bundles ◽  
The Brain

Abstract Background Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. Methods TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD. Results Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups. Conclusions Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.

scholarly journals Pattern of Presentation of Neurocutaneous Syndromes in a Tertiary Care Hospital of Bangladesh

2019 ◽  
Vol 43 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Gopen Kumar Kundu ◽  
Sanjida Ahmed ◽  
Shaheen Akhter ◽  
Md Nasir Hossain ◽  
Rana Kumar Biswas
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Ataxia Telangiectasia ◽  
Autism Spectrum ◽  
Care Hospital ◽  
Cutaneous Manifestations ◽  
Weber Syndrome ◽  
Sturge Weber Syndrome ◽  
Neurocutaneous Syndrome ◽  
Neurocutaneous Syndromes

Background: Neurocutaneous syndromes (NCS) represent a group of central nervous system disorders associated with lesion in the skin, eye and possibly other visceral organs. Various cutaneous manifestations usually appear early in life, progress with time but neurological features generally present at a later age. The objective of this study is to observe the frequency of pattern and presentation of various forms of neurocutaneous syndrome. Methodology: A descriptive cross sectional study was conducted at department of Paediatric Neurology of Bangabandhu Sheikh Mujib Medical University(BSMMU), Dhaka, Bangladesh from March, 2015 to February, 2016. Children (3month to 8 years) with NCS, diagnosed on the basis of standard diagnostic criteria for different NCS were included and compared. Results: Among of 27 children,16 (59.26%) boys, 09(40.74%) girls with neurocutaneous syndrome, mean age of presentation was 38.67±18.57 (range 3 month to 84 months). The various forms of NCS observed were Tuberous sclerosis complex (48.14%), Ataxia telangiectasia (29.62%), Sturge Weber Syndrome (14.81%), Neurofibromatosis1(3.7%) and Linear nevus syndrome (3.7%). In Tuberous sclerosis complex , most common feature was facial angiofibroma ( 92.30%), Hypomelanotic macule (76.90%), Shagreen patch (76.90%). In Ataxia telangiectasia, commonest presentation was ataxia 8(100%) followed by ocular telangiectasia (62.50%). In Sturge weber syndrome, commonest presentation was facial capillary malformation (100%). Neurofibromatosis patient presented with café-au-lait spot (100%). Common systemic manifestations of NCS were found in TSC and those were multicystic kidney disease (30.76%), autism spectrum disorder (15.38%) & attention deficit hyperactivity disorder (7.69%). Conclusion: In our study, the commonest neuro-cutaneous syndrome is tuberous sclerosis complex and it’s cutaneous manifestation is facial angiofibroma Bangladesh J Child Health 2019; VOL 43 (1) :15-20

scholarly journals Neuro‐epileptic determinants of autism spectrum disorders in tuberous sclerosis complex

Brain ◽  
2002 ◽  
Vol 125 (6) ◽  
pp. 1247-1255 ◽  
Author(s):  
Patrick F. Bolton ◽  
Rebecca J. Park ◽  
J. Nicholas P. Higgins ◽  
Paul D. Griffiths ◽  
Andrew Pickles
Keyword(s):  
Autism Spectrum Disorders ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autism Spectrum ◽  
Spectrum Disorders
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