An Animal Model Of Adolescent Harsh Physical Abuse

Progress imaging human brain structure and function has been extensive over the past 3 decades. Methods to show brain atrophy and hypertrophy are available. Correlations and complex mathematical models can be devised that relate disease symptoms with functional brain changes. Also, many regions are almost always engaged in a single function that are termed networks. Each node in the network has a unique contribution to a particular function(s) and cingulate cortex is one such node in many networks because it is engaged in many functions.

As shown in previous sections, ACC and MCC express structural and functional damage in disorders like PTSD and depression in patients with histories of child abuse (Kitayama et al., 2006; Tottenham et al., 2010; Wooodward et al., 2005; Shin et al., 2004, 2009). Child abuse itself reduces ACC volume (Cohen et al., 2006; Mangilo, 2010; Breslow et al., 2006; Dannlowski et al., 2012; Ansell et al., 2012). PTSD patients also have high levels of diffuse pain and child harsh abuse/rape affects them into adulthood.

There are, however, drawbacks to studying brain changes evoked by human child abuse and rape. The biggest problem is heterogeneity; i.e., all children/adolescents have different genetic makeups, find themselves in different contexts during the abuse, the abuse can occur at different times of their life, the relationship of the abuse to evoked symptoms (fear, anxiety, stress, pain) can be quite complex in the brain and evolves over time into different disease states as discussed in “Adult-onset Psychopathologies.” Indeed, children do not become aware of their abuse often for decades after the experiences and their reports often only become useful in late adolescence (ages 20-25 and beyond). Thus, there are so many unknowns when working with abused children, it is almost impossible to determine cause and effect in terms of their experiences much less to access their brains for biochemical and neuropathological analyses.

This brings us to the issue of using animal models. Animal models are one of the workhorses of biomedical research. For example, gene editing is a promising cure for HIV/AIDS by removing the HIV-1 proviral DNA. This is being done in mice (Yin et al., 2017) but much of the early work with HIV-AIDS was done with Simian viruses in non-human primates. In terms of our work, all mammals can be abused. However, no neuroscientist thinks that an animal experiences the same perceptions of abuse as humans. However, animals are required for 4 reasons. First, the same genetic strain can be used such that genetic differences play a minor role in variability of responses to abuse. Second, the onset, duration, and characteristics of the physical abuse can be standardized, while in humans most of these factors can only be estimated. Third, although animals cannot tell us about their internal feelings, they can be tested behaviorally and provide a window into their world of abuse. Fourth, the brains can be removed to explore protein and neuron changes that occur during and after the abusive events. This is a critical issue as it will lead eventually to identifying what networks (connected nodes) are involved and how to fix them soon after the abusive events.

Thus, animals provide a standardized approach to abuse, brain changes and possible treatments to block adult-onset psychopathology. The goal of such work is to devise effective rational, brain-based strategies that have not emerged from human imaging studies.

Animal studies show that ACC is critical for contextual fear memory as nCRD evokes conditioned place avoidance mediated by ACC (Johanson et al., 2001; Yan et al., 2012) and is activated by remote contextual fear (Figueirdo et al., 2003). Some animals in our model were vulnerable as shown in a contextual fear task (withheld moving) and some resilient (jumped right into the testing area). There was no sign of ongoing abdominal pain in these animals. We demonstrated that many changes occur in ACC and aMCC.

The nociceptive (pain)-stress conditioning of our rabbits is a model of harsh physical abuse and this is our starting point for future studies. With it we will be able to explore the entire brain for changes in proteins and neuron and dendrite atrophy or death. We will be able to follow brain changes over time into adulthood and hope that rational treatments will result that will block such changes including adult-onset psychopathologies.

We are in need of your support to implement these next generation studies; particularly from the survivor community that understands the short- and long-term consequences of child abuse.