An Introduction: Quantification of the Hippocampal BDNF Content of Maternally Separated Rats Using a Western Blot Protocol

Among industrialized nations, the United States has the worst incidence of child maltreatment with 3 million cases per year (U.S. Department of Health and Human Services, 2012). Studies have shown that individuals who were maltreated when they were young are more susceptible to drug abuse such as alcohol, cocaine, and nicotine (Maddahian, Newcomb, & Bentle, 1988). Early life stress (ELS) causes hyperactivation of the Hypothalamic-Pituitary- Adrenal (HPA) Axis (Heim et al., 2000; Plotsky et al., 2005). The dysregulation of the HPA axis causes the secretion of glucocorticoid stress hormones by large amounts, which in return attenuates hippocampal Brain-derived neurotrophic factor (BDNF) (Smith, Makino, Kvetnansky, & Post, 1995). BDNF is a neurotrophin that helps the growth, maintenance, and survival of neurons and is also involved in neuronal plasticity. To mimic ELS, maternal separation is used as an animal model. Studies have shown that adult maternally separated rats have decreased hippocampal mature BDNF (Lippman et al., 2007). Exercise alters some of the effects of ELS by protecting hippocampal BDNF from the down-regulation caused by the hyperactivation of HPA axis (Maniam & Morris, 2010; Neeper et al., 1996). The purpose of this research is to investigate the effects of ELS and exercise on behaviors related to substance abuse and hippocampal BDNF content. When we attempted to measure hippocampal BDNF by the enzyme-linked immunosorbent assay (ELISA), we did not observe the previously-published down-regulation of BDNF in the hippocampi of maternally separated animals (Dold, 2013). Thus, a western blot protocol was developed for the quantification of BDNF in the same protein samples that were previously quantified using ELISA. Western blot is more specific in targeting protein due to SDS-page capability to separate protein components in accordance to their size. BDNF undergoes post-translational processing, such that both pro- BDNF (the 32 kD precursor) and mature BDNF (14 kD) are present and biologically active in rat brain tissue. Thus, western blot will allow us to distinguish between these BDNF proteins, which is important in our study since we are primarily interested in mature BDNF. We expect maternal separation (MS) to attenuate the hippocampal mature BDNF content. Furthermore, we expect that the mature BDNF content will positively correlate with the total running activity

Alzheimer’s in America: Effective Physical Activity Methods for Brain Health Reviewed

The alarming rise in rates of Alzheimer’s disease indicates that there is an immediate need for a solution. According to the Centers for Disease Control and Prevention (2014) Alzheimer’s is currently the sixth leading cause of death in the United States. Over 400,000 new cases are diagnosed each year and these numbers are only expected to rise (Centers for Disease Control, [CDC] 2014). One out of nine people are living with the disease and 84,000 people succumb to this disease every year in America; currently there is no cure or direct treatment plan for the disease (Alzheimer’s Association, [AA] 2010; National Institute on Aging, [NIH] 2015). These numbers are very significant; almost a quarter of the population diagnosed dies every year. Being that Alzheimer’s is a leading cause of death, its presence cannot be ignored. The lack of a cure encourages researchers to seek out protective interventions in order to decrease the risk of developing the disease in later life. The purpose of this study will be to assess the effect of physical activity in middle adulthood on delaying the onset of Alzheimer’s disease. This study will identify trends in ongoing physical lifestyle activities that reduce the entire population’s chance of developing the disease in later life. This will contribute to previous research by focusing on prevention to reduce risk of cognitive decline and implementing a suggested intervention for middle-aged adults that will decrease the likelihood of Alzheimer’s being developed and help to delay the progression

Effects of Restraint Stress and Allopregnanolone Inhibition on Amphetamine Locomotor Sensitivity

The chronic, recurring nature of addiction remains a worldwide problem. Even after apparently successful clinical treatment and long term abstinence, individuals may still relapse many months or years later. Although many individual differences exist among substance abusers, relapse tends to occur during periods of high stress (Sinha et al., 2006). Behavioral training and therapy can help cope during these high stress times, but pharmacological interventions have not been shown to be effective (Ross & Peselow, 2009). Although some therapeutic options decrease relapse rates, more effective treatments for relapse need further consideration. The effect of stress on use of and relapse to drugs of abuse likely stems from coupled stress and reward circuits in the brain. Stress leads to increased release of stress-related hormones including 3α, 5α tetrahydroprogesterone or, allopregnanolone (Purdy et al., 1991). Allopregnanolone is a neurosteroid tied to several brain circuits involved with stress and reward. Elevated levels of this neurosteroid occur throughout the mammalian brain and periphery after cocaine administration, and rats show enhanced dopamine release in the nucleus accumbens after an injection of finasteride, which inhibits the enzymes (5-α reductase I) responsible for allopregnanolone synthesis (Dazzi et al., 2002). Finally, acutely stressed rats exhibit increased dopamine release in the prefrontal cortex after an injection of finasteride, further indicating allopregnanolone’s involvement with brain reward systems (Devoto, 2012). Based on this information, we hypothesized that administration of finasteride would result in increased stress induced amphetamine locomotor sensitization

The effect of early environmental manipulation on locomotor sensitivity and methamphetamine conditioned place preference reward

Early life stress leads to several effects on neurological development, affecting health and well-being later in life. Instances of child abuse and neglect are associated with higher rates of depression, risk taking behavior, and an increased risk of drug abuse later in life. This study used repeated neonatal separation of rat pups as a model of early life stress. Rat pups were either handled and weighed as controls or separated for 180 min per day during postnatal days 2–8. In adulthood, male and female rats were tested for methamphetamine conditioned place preference reward and methamphetamine induced locomotor activity. Tissue samples were collected and mRNA was quantified for the norepinephrine transporter in the prefrontal cortex and the dopamine transporter in the nucleus accumbens. Results indicated rats given methamphetamine formed a conditioned place preference, but there was no effect of early separation or sex. Separated males showed heightened methamphetamine-induced locomotor activity, but there was no effect of early separation for females. Overall females were more active than males in response to both saline and methamphetamine. No differences in mRNA levels were observed across any conditions. These results suggest early neonatal separation affects methamphetamine-induced locomotor activity in a sex-dependent manner but has no effects on methamphetamine conditioned place preference