User:Grahamal/Animal model of autism

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Another goal of the use of rodent models to study autism is to identify the mechanism by which autism develops in humans. It is important, however, to acknowledge the limitations of using rodent models to fully replicate the complexity of ASD seen in humans. Many behavioral assays employed in these models may lack direct engagement with similar neural circuitry observed in humans, and therefore, may lack translational face validity. While certain behaviors in rodent models may bear apparent resemblance to ASD symptoms, particularly social communication deficits and restrictive and repetitive behaviors, it's essential for researchers to avoid overstating the relevance of these model systems. Not every behavioral feature in an animal model may be expected to perfectly mirror the intricate and heterogeneous features of neurodevelopmental disorders (NDDs) in humans. Other researchers have developed an autism severity score to measure the degree of severity of the mice's autism, as well as the use of scent marking behavior and vocalization distress as models for communication.

Maternal immune activation has also been associated with increased risk for development of neurodevelopmental disorders. Maternal immune activation is when inflammatory pathways are activated during pregnancy, usually by an infection. These inflammatory pathways involve the release of cytokines, or immune signaling proteins, Recent studies have shown that changes in the expression of cytokines during early stages of life are linked to the likelihood of experiencing neurodevelopmental disorders such as autism spectrum disorder (ASD) and significant developmental delay.

Changes made from peer review:

Changed the wording to Recent studies have shown that changes in the expression of cytokines during early stages of life are linked to the likelihood of experiencing neurodevelopmental disorders such as autism spectrum disorder (ASD) and significant developmental delay. This was feedback from peytonmk. I also plan to take her suggestion to make a separate paragraph for the second reference and add more updated research on how animal models help to identify the mechanism for ASD development in humans.

Changed "crucial" to "important" to not make the tone sound opinionated, this feedback was from sara8887. I am also going to add references that are relatively more up to date.

Continuing to edit article:

Environmental Factors of ASD

Looking at the environmental factors of autistic spectrum disorder in rodents helps us to understand the neuropathology of the disorder which can be compared to humans. Environmental factors have been studied in animal rodent models and have been seen to influence brain development and play a role in CNS neuropathology gene expression. For example, one study found that a possible environmental contributor to autism may be agents like prenatal exposure to air pollution or any birth difficulty leading to periods of oxygen deprivation to the brain, which alter serotonin levels in early development of the rodent¹. This study also found that if the parent exhibits autism, the offspring are more likely to be autistic as well and that since older men have a higher number of DNA mutations in their sperm, these mutations are usually found in the offspring of older men. The last major result that this study observed was that environmental factors during and after pregnancy may have an impact on the immune system as well as the developing nervous system and plays a part in creating neurodevelopmental disorders like autism¹. Recent advancements in research on ASD in rodent models illustrate that the interaction between genetic predispositions and environmental exposures. These exposures, which span from prenatal factors such as maternal infections and diet to postnatal experiences including exposure to toxicants, insecticides, and certain medications, are increasingly recognized for their critical roles in the neuropathology of ASD. Specifically, a detailed analysis recognizes how these factors may heighten the susceptibility to developing ASD disrupting the neurodevelopmental process. Studies have observed an increase in immune cells of the prefrontal cortex and an augmentation of support cells in the hippocampus due to toxins in rodent models, particularly those treated with valproic acid (VPA). This link between environmental exposures and distinct neurobiological alterations remains unpredictable largely due to the variability of timing. Since environmental factors can occur at any time during the developmental process, there is much variability in the neural and behavioral phenotype of autism. The environment can cause unknown changes in brain development of rodents because they don't all live in the same habitat and therefore might develop different changes to their brain than what is expected.

Rodent model

It has been observed that mice lacking the gene for oxytocin exhibit deficits in social interaction, and that it may be possible to develop treatments for autism based on abnormalities in this and other neuropeptides. A mutation in the Cntnap2 gene, which has been linked to ASD in human, results in decreased oxytocin levels in mice. Supplementing affected mice with oxytocin has been found to improve these social deficits, indicating potential therapeutic insights for improving social behaviors in this model. However, recent studies have emphasized that the majority of risk factors identified for autism do not directly connect to the oxytocin signaling pathway. This highlights that while oxytocin's role is significant, ASD is complex with a wide array of genetic influences, many of which may affect different biological pathways not directly related to oxytocin.

Songbird model

In 2012, a researcher from the University of Nebraska at Kearney published a study reviewing research that had been done using the zebra finch as a model for autism spectrum disorders, noting that the neurobiology of vocalization is similar between humans and songbirds, and that, in both species, social learning plays a central role in the development of the ability to vocalize. These parallels extend to the FOXP2 gene, expressed significantly in various parts of CNS, including areas crucial for motor functions, from embryonic development through adulthood. Other research using this model has been done by Stephanie White at the University of California Los Angeles, who studied mutations in the FOXP2 gene and its potential role in learned vocalization in both songbirds (specifically the zebra finch) and humans. Further research has elucidated how FOXP2 and its associated gene FOXP1 are distributed in language- related brain centers, influencing vocal learning through mechanisms that affect the formation of vocalization- related memories and the neural substrates of song and speech. In zebra finches, knockdown of FOXP2 in the basal ganglia song nucleus Area X impairs singing, supporting the gene's role in the regulation of song production. Younger birds with knocked down FOXP1 expression have displayed selective learning deficits, impacting their ability to form memories essential for the cultural transmission of behavior, such as learning adult model songs.