Hippocampus Glucocorticoid Receptor (HPA)

The genome is the complete set of an individual’s inheritable traits or it’s DNA. As a fetus develops, signals are received that cause incremental change in the gene expression patterns. The DNA in our bodies is wrapped around proteins called histone. The histone and DNA are covered in chemical tags. This structure is called an epigenome. The epigenome shapes the structure of the genome. Epigenetic marks are modifications of DNA and histones. The epigenome tightly wraps inactive genes and allows active genes to be more easily accessible. The epigenome adjusts specific genes in response to our changing environment. The programming of neurons through epigenetic mechanisms is critical in neural development. A type of cellular memory is formed when those changes occur. These are epigenetic tags. Each tag records the cell’s experiences on the DNA. This is to help stabilize gene expression. Over time, and with thousands of different experiences, an epigenetic profile forms for each cell type. Each one is unique, with a distinct identity and a specialized function. A flexible epigenome allows us to adjust and learn from our mistakes. The epigenome responds to signals. These signals come from a variety of places. From fetal development to old age, our epigenome is effected by our environmental factors.

Child maltreatment can lead to pathology through a biological avenue via epigenetics. The stress, both emotional and physical involved in any form of maltreatment, have the potential to trigger various epigenetic mechanisms that regulate gene expression. These mechanisms are of course not limited to the nervous system, but for the sake of argument in psychopathology, these are what we are

It is often thought that our DNA is a concert blue print and the way we personally engage with the environment has no effect on our future generation. However through experiments and recent studies, scientists have discovered external environmental factors can effect ones DNA sequence. It was found that genes have the ability to switch on and off and affect how cells read genes. This new avenue is called Epigenetics. Epigenetics is the study of heritable changes in gene expression. It describes the outward phenotypic appearance that is not the result to changes in the DNA sequence but instead, changes to the chemical tags that overlay the genome. Epigenetics is often described as the missing link between the environment an individual is exposed

Upon activation by an emotional or physical stressor, corticotropic releasing hormone (CRH) is released from the paraventricular cells of the hypothalamus and exerts its effect on the anterior pituitary gland Here, CRH stimulates the synthesis of adrenocorticotropic hormone (ACTH) and its release into the bloodstream [19,20]. In turn, ACTH acts on receptors of the adrenal cortex to stimulate the synthesis and release of cortisol [19,20]. Also known as the body’s ‘‘stress hormone’’, cortisol travels through the blood in both protein-bound (inactive) and free (active) forms. Cortisol can act to limit its own synthesis via a negative feedback mechanism to the hypothalamus and pituitary gland [19,20]. Upon reaching a target cell, free cortisol diffuses through the cell membrane to bind to the cytoplasmic glucocorti- coid receptor [19,20]. This ligand-receptor complex translocates to the nucleus where it binds glucocorticoid-response elements to affect transcription of target genes [19,20]. As our body’s central glucocorticoid, cortisol has many actions. These include gluconeogenesis, lipolysis, modulating the immune system, increase of blood pressure and insulin resistance [19,20]. Cortisol is metabolized by 11-beta hydroxysteroid dehydrogenase type 2 to its inactive form, cortisone [19,20 GOW

To understand epigenetics and transgenerational epigenetics in greater detail we need to obtain a clearer picture of the underlying molecular mechanisms. Lim and Brunet (2013) revealed that environmental stimuli can influence the chromatin structure by noncoding RNAs- including siRNA (small interfering RNA, worm), piRNA ((Piwi-interacting RNA, worm and fly), viRNA (small interfering RNAs derived from virus, worm), miRNA (micro RNA, mice)- DNA methylation (mice, rat) and histone modification (with the help of Histone methyltransferase poteins)- H3K4me2/3 (worm), H3K36me3 (worm), H3K36me3 (worm, fly), H3K9me2/3 (worm, fly), H3K27me3 (mice, human). Prion proteins might also play role (yeast). These changes might influence the metabolics, which changes the expression of different chemicals and are themselves potential environmental stress factors; thus, they could initiate epigenomic changes. Chromatin modifications

A: The hypothalamus controls hormone release mainly through the pituitary gland by sending signals in the form of releasing hormones to prompt the anterior lobe to secrete them as the main function of the pituitary gland is hormone secretion into the body. The anterior lobe is responsible for the release of crucial hormones including; growth hormone, follicle stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, thyroid stimulating hormone and finally prolactin.

The different events and social behaviors that different animals were exposed to in infancy effected their physiology and behavior and those effects were far reaching and long lasting, following them for the rest of their lives. Experiences and environmental factors cause epigenetic changes to genes, but the influence is even further reaching that that. Epigenetic influences even occur in utero, the mother passes on more than her genetic material. The fetus’s epigenetics are influenced by the experiences of the mother during pregnancy, things like the mother’s diet and stress levels can influence her offspring later in life. We are all born into different circumstances and situations. Location and socioeconomic status vary greatly among the human population. The influence that epigenetic factors have on how our genes are expressed can be helpful to aide in how we navigate our own lives in relation to the specific set of circumstances we are born into. The way our genes are influenced by out mother (during pregnancy) can aid us in adapting to the specific “world” we are born

While the mice in the experiments had no gene modifications/mutations, genes were turned off/on when environmental factors were altered, creating a variety of unexpected traits in the offspring of mice (Moalem 159-160). These factors are hard to account for and are good examples of how genetic information varies greatly and is not perfect. Understanding of genetic variation and methylation is difficult and is a complex topic being

Another experiment studies maternal separation in mice that showed one to three hours of separation per day throughout the postnatal period induced multiple changes with neuroendocrine and neuropeptide systems; consequently, these changes precipitated a heightened HPA (hypothalamic-pituitary-adrenal) axis response to stress due to brain region-specific epigenetic alterations that were induced through the reductions of maternal care experienced (Champagne, 2012, p43). The observation is consistent with the effect of social neglect on development in human infants. Exposure to an environment of maternal separation can produce a sensitive stress response and impairment with spatial memory. Epigenetic effects of the have also been

Farah et al. (2008) noted that “Prolonged maternal separation…has been shown to exert lasting negative effects on hippocampal development (p. 794) which negatively affects memory and stress regulation later in life. In addition, in a study done with children in Quebec, Canada, Lupien et al. (2000) found that a child with a depressive mother was more likely to have high salivary levels of cortisol. High levels of the stress hormone cortisol have been linked to “Cognitive deficits and atrophy of brain structures involved in learning and memory” (as cited in Lupien, King, Meaney, & McEwan, 2000, p. 979). Further, studies done with rats have shown that limited variety in their cage environment negatively influences brain structures such as the number of neurons, glial cells, dendrites, and synapses (Farah et al., 2008). As these studies show, a non-nurturing and or high stress environment can inhibit a child’s proper brain development that has been associated with problems later in the child’s life.

On one occasion, they sorted mother rats into 2 different categories: highly attentive, and highly inattentive towards offsprings. After the pups of each groups grew into adulthood, the team analyzed their hippocampus (a brain region correlated to stress). Szyf and Meaney found in pups of inattentive mothers, genes regulating glucocorticoid (regulates stress sensitivity) are highly methylated compared to pups of attentive mothers. Methylated genes are harder to transcribe, causing behavioral changes in the pup's ability to manage stress. On another occasion, Szyf and Meaney gave pups born from attentive mother to inattentive ones and vice versa. Pups who were raised by inattentive mothers also showed methylation on glucocorticoid genes, supporting the notion that maternal care plays a large role on gene expression. Szyf and Meaney also mentioned that the timing of when the methylation happens is also important. Changes on gene methylation early on in life (0-2 years) showed stronger effects compared to middle age changes.

Glucocorticoids dramatically reduce the manifestations of inflammation. This is due to their profound effects on the concentration, distribution, and function of peripheral leukocytes and to their suppressive effects on the inflammatory cytokines and chemokines and on other mediators of inflammation. Inflammation, regardless of its cause, is characterized by the extravasation and infiltration of leukocytes into the affected tissue. These events are mediated by a complex series of interactions of white cell adhesion molecules with those on endothelial cells and are inhibited by glucocorticoids. After a single dose of a glucocorticoid, the concentration of neutrophils in the circulation increases while the lymphocytes (T and B cells), monocytes, eosinophils, and basophils decrease. The changes are maximal at 6 hours and are dissipated in 24 hours. The increase in neutrophils is due both to the increased influx into the blood from the bone marrow and to the decreased

It is well-known that the parahippocampal region is the central organization of neural processes for memory and learning. In this region, entorhinal cortex (EC) is an interface between hippocampus and neocortex, which largely transfers the information by spiny stellate cells (SCs). The electrophysiological properties of SCs are identified by 4-18 (Hz) STOs following subthreshold stimuli [1,2]. These STOs are believed to be important contributors to the hippocampal theta rhythm [3]. STOs are small-amplitude oscillations (maximum amplitude ~ 10 mV) of membrane potential that are closely related to the synchronous rhythmic activities in many neurons, which is associated with crucial functions of the nervous system, such as perception [4], learning

Epigenetics is a field of study concerning genetic modifications due to changes in gene expression, rather than changes in the gene itself. There are countless epigenetic modifications that regulate gene expression, such as DNA Methylation or Gene Silencing, and all of these changes, if they occur in the germline, are preserved through DNA multiplication, and thus will be passed on to progeny. Moreover, these alterations can also take place in the somatic cells of the body and still be passed on to the next generation, through an interrelated alteration that takes place in the germline cells. It is this observation that has baffled scientists for generations, as it is an idea that truly lies at the heart of the “nature vs. nurture” argument.

Today, it is agreed upon that both, nature and nurture, work together to convey adaptive behaviors. Many researchers, like Champagne (2009), use the term “epigenetic” to explain the vigorous interaction among genes and the environment. Recent studies have proved that epigenetic effects are a process through which the condition of the social environment becomes rooted in at a biological level.