Nature Reviews Neuroscience 11, 490-502 (July 2010) | doi:10.1038/nrn2851
Behavioural phenotyping assays for mouse models of autism
Jill L. Silverman, Mu Yang, Catherine Lord & Jacqueline N. Crawley
Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100–150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of austism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.
Mice Exposed to Diagnostic Ultrasound In Utero Are Less Social and More Active in Social Situations Relative to Controls.
McClintic AM, King BH, Webb SJ, Mourad PD.
Department Neurological Surgery, University of Washington, Seattle, Washington.
Clinical use of diagnostic ultrasound imaging during pregnancy has a long history of safety and diagnostic utility, as supported by numerous human case reports and epidemiological studies. However, there exist in vivo studies linking large but clinically relevant doses of ultrasound applied to mouse fetuses in utero to altered learning, memory, and neuroanatomy of those mice. Also, there exists a well-documented significant increase in the likelihood of non-right-handedness in boys exposed to diagnostic ultrasound in utero, potentially relevant given the increased prevalence of autism in males, and reports of excess non-right-handedness in this population. Motivated by these observations, we applied 30 minutes of diagnostic ultrasound to pregnant mice at embryonic day 14.5 and assayed the social behavior of their male pups 3 weeks after their birth. The ultrasound-exposed pups were significantly (P < 0.01) less interested in social interaction than sham-exposed pups in a three-chamber sociability test. In addition, they demonstrated significantly (P < 0.05) more activity relative to the sham-exposed pups, but only in the presence of an unfamiliar mouse. These results suggest that fetal exposure to diagnostic ultrasound applied in utero can alter typical social behaviors in young mice that may be relevant for autism. There exist meaningful differences between the exposure of diagnostic ultrasound to mice versus humans that require further exploration before this work can usefully inform clinical practice. Future work should address these differences as well as clarify the extent, mechanisms, and functional effects of diagnostic ultrasound's interaction with the developing brain. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
*Note: Mouse models of autism rely on studying symptoms, and are infantile. http://www.nature.com/nrn/journal/v11/n7/full/nrn2851.html
This just goes to show that ultrasound will soon be used to enhance the treatment of a variety of diseases. Metabolic disorders and neuropathology, too.
The overall prognosis for malignant glioma is extremely poor, and treatment options are limited in part because of multidrug resistant proteins. Our previous findings suggest low intensity ultrasound (LIUS) can induce apoptosis of glioma cells. Given this finding, we were interested in determining if LIUS could help treat glioma by inhibiting multidrug resistant proteins, and if so, which pathways are involved. In this study, the toxicity sensitivity and multidrug resistance proteins of glioma induced by LIUS were investigated using CCK-8, immunohistochemistry, immunofluorency, and RT-PCR in tissue samples and cultured cells. LIUS inhibited increase of C6 cells in an intensity- and time-dependent manner. The toxicity sensitivity of C6 cells increased significantly after LIUS sonication (intensity of 142.0 mW/cm2) or Doxorubicin (DOX) at different concentration, particularly by the combination of LIUS sonication and DOX. The expressions of P-gp and MRP1 decreased significantly post-sonication at intensity of 142.0 mW/cm2 both in vitro and in vivo. The expressions of p110 delta (PI3K), NF-κB-p65, Akt/PKB, and p-Akt/PKB were downregulated by LIUS sonication and DOX treatment separately or in combination at the same parameters in rat glioma. These results indicate that LIUS could increase the toxicity sensitivity of glioma by down-regulating the expressions of P-gp and MRP1, which might be mediated by the PI3K/Akt/NF-κB pathway.
A survey in 2006 found that only 3.8% of sonographers could correctly explain the safety readout on an ultrasound machine. This is unacceptable.
Watch this video to learn more about shortcomings in sonographer education worldwide. This is important if you plan on having children any time soon.
A few years ago, a 12 year old girl was admitted to a hospital for heart murmurs. A defective ultrasound transducer was used and they could not detect why the murmurs occurred. Repeating this procedure (nearly 2 years later) with a different machine showed dramatically different results.
This prompted a study in which 32 hospitals were censused for the efficacy of their ultrasound units. 39.8% of transducers were found defective.
Sonographers cannot tell when a transducer is defective intuitively, it just makes the picture worse. Oftentimes they will compensate by turning up the power to get a more clear image. Ob-Gyn ultrasound suffers the same problem, and this will expose our children to unnecessarily high intensities.
Watch the video to learn more -
This video is a review of what science currently understands about the safety of prenatal ultrasonography.
The short version: medicine does not yet fully understand how ultrasound affects the body, and there has been little research into it. When a practitioner tells you that sonography is perfectly harmless/completely safe, that is not backed by scientific evidence.
Considering that almost every woman in the world gets an ultrasound (or more) during pregnancy, this is unacceptable.
Transvaginal ultrasound is when a sonographer inserts an ultrasound transducer into a woman’s vagina for internal imaging. They can detect a variety of conditions, including but not limiting to cancers or other growths, fluid deposits, bone damage, . . . it is useful for many valid diagnostic reasons.
There are, however, some risks associated with having the transducer closer to the fetus: One study detected damage in microvilli extracted from fetuses exposed to transabdominal ultrasound, but not transvaginal for the same duration: http://www.ncbi.nlm.nih.gov/pubmed/11776185
[Influence of sonographic examination on embryo villi during early pregnancy].
To evaluate the effects of sonographic examination on embryo villi during early pregnancy.
Eighty early pregnant women intended for artificial abortion were divided into 4 groups: group I served as control, the remaining 3 groups underwent pelvic sonographic examination transabdominally for 10 minutes (group II), transvaginally for 3 minutes (group III) or for 10 minutes (group IV) respectively. After 1 hour embryo villi were obtained through artificial abortion and examined by electronic microscopy, biochemical methods and sister chromatid exchanges (SCE).
In group IV, but not group II, III, the embryo microvilli were found broken, lost and disarranged. The rough endoplasmic reticulum of trophoblasts expanded. Their malondial dehyde levels increased while the superoxide dismutase (SOD) decreased as compared with control (P < 0.01). There was no difference of SCE among these 4 groups.
It is recommended that sonographic examination should be done through abdominal approach for shorter than 10 minutes during early stage of pregnancy.