Search

Background: Emerging research points to innate immune mechanisms in the neuropathological and behavioral consequences of heavy alcohol use. Alcohol use is common among people living with HIV infection (PLWH), a chronic condition that carries its own set of long-term effects on brain and behavior. Notably, neurobiological and cognitive profiles associated with heavy alcohol use and HIV infection share several prominent features. This observation raises questions about interacting biological mechanisms as well as compounded impairment when HIV infection and heavy drinking co-occur.Objective and Method: This narrative overview discusses peer-reviewed research on specific immune mechanisms of alcohol that exhibit apparent potential to compound the neurobiological and psychiatric sequelae of HIV infection. These include microbial translocation, systemic immune activation, blood-brain barrier compromise, microglial activation, and neuroinflammation.Results: Clinical and preclinical evidence supports overlapping mechanistic actions of HIV and alcohol use on peripheral and neural immune systems. In preclinical studies, innate immune signaling mediates many of the detrimental neurocognitive and behavioral effects of alcohol use. Neuropsychopharmacological research suggests potential for a feed-forward cycle in which heavy drinking induces innate immune signaling, which in turn stimulates subsequent alcohol use behavior.Conclusion: Alcohol-induced immune activation and neuroinflammation are a serious health concern for PLWH. Future research to investigate specific immune effects of alcohol in the context of HIV infection has potential to identify novel targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

As in many fields of neuroscience, alterations in brain morphology, and specifically gray matter volume and cortical thickness, have been repeatedly linked to chronic pain disorders. Numerous studies have shown changes in cortical and subcortical brain regions suggesting a dynamic process that may be a result of chronic pain or contributing to a more generalized phenomenon in chronic pain including comorbid anxiety and depression. In this review, we provide a perspective of pain as an innate state of pain based on alterations in structure and by inference, brain function. A better neurobiological understanding of gray matter changes will contribute to our understanding of how structural changes contribute to chronic pain (disease driver) and how these changes may be reversed (disease modification or treatment). [ABSTRACT FROM AUTHOR]

Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programing of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal--embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programing offspring stress pathway dysregulation and the importance of sex. [ABSTRACT FROM AUTHOR]

On February 3, 2010, a “Letter of Concern from Bioethicists,” organized by fetaldex.org, was sent to report suspected violations of the ethics of human subjects research in the off-label use of dexamethasone during pregnancy by Dr. Maria New. Copies of this letter were submitted to the FDA Office of Pediatric Therapeutics, the Department of Health and Human Services (DHHS) Office for Human Research Protections, and three universities where Dr. New has held or holds appointments. We provide a critical appraisal of the Letter of Concern and show that it makes false claims, misrepresents scientific publications and websites, fails to meet standards of evidence-based reasoning, makes undocumented claims, treats as settled matters what are, instead, ongoing controversies, offers “mere opinion” as a substitute for argument, and makes contradictory claims. The Letter of Concern is a case study in unethical transgressive bioethics. We call on fetaldex.org to withdraw the letter and for co-signatories to withdraw their approval of it. [ABSTRACT FROM AUTHOR]

Stressors differ in their physiological and behavioral outcomes. One of the major mechanisms by which stressors affect the brain and behavior is alteration in neuronal plasticity. We investigated in the rat the effects of a single exposure to psychophysical (electrical foot shock) vs. psychological (social defeat) stressors on anxiety- and depression-related behaviors, serum levels of corticosterone and the expression of plasticity-related genes CAM-L1, CREB, GAP-43, and laminin in the prefrontal cortex (PFC), the amygdala and the hippocampus. Rats were examined for 24 h or 1 week after the exposure to stress. Footshocks enhanced anxiety-related behaviors, whereas social defeat induced depression-related behaviors at both time points and less pronounced anxiety 1 week post-exposure. Serum corticosterone concentrations were enhanced 24 h after shocks, but only 1 week after exposure to the social stressor. Moreover, the shock-stressed rats exhibited decreased CAM-L1 protein level in the hippocampus 24 h post-exposure and decreased GAP-43 protein level in the PFC 1 week post-exposure. By contrast, the social stressor enhanced expression of the plasticity-related proteins in the amygdala and the hippocampus, mostly 1 week after the exposure. These results indicate stressor-specific time-dependent changes in different neuronal pathways, and suggest consideration of a cause-specific approach to the treatment of stress-related disorders. [ABSTRACT FROM AUTHOR]

Many studies have shown that early life stress may lead to impaired brain development, and may be a risk factor for developing psychiatric pathologies such as depression. However, few studies have investigated the impact that early life stress might have on the onset and development of neurodegenerative disorders, such as Parkinson's disease, which is characterized in part by the degeneration of dopaminergic neurons in the nigrostriatal pathway. The present study subjected rat pups to a maternal separation paradigm that has been shown to model adverse early life events, and investigated the effects that it has on motor deficits induced by a unilateral, intrastriatal injection of 6-hydroxydopamine (12 μg/4 μl). The female rats were assessed for behavioral changes at 28 days post-lesion with a battery of tests that are sensitive to the degree of dopamine loss. The results showed that rats that had been subjected to maternal separation display significantly impaired performance in the vibrissae and single-limb akinesia test when compared to normally reared animals. In addition, there was a significant increase in the loss of tyrosine hydroxylase staining in maternally separated rats. Our results therefore suggest that adverse experiences sustained during early life contribute to making dopamine neurons more susceptible to subsequent insults occurring during more mature stages of life and may therefore play a role in the etiopathogenesis of Parkinson's disease. [ABSTRACT FROM AUTHOR]

The use of pharmaceutical products such as Piracetam (Nootropil®) for the treatment of learning disabilities is becoming increasingly prevalent, and some studies have shown successful treatment of learning disabilities in children. This research article will discuss traditional uses of Piracetam, as well as uses in learning disabilities, with particular focus on case studies where it has been given to children with learning disabilities. Furthermore, we investigate how Piracetam could potentially enhance learning, with specific focus on brain areas. However, even though Piracetam may enhance learning, the question that arises is how safe it is at a cellular level. Therefore the effect of Piracetam at a cellular level was determined. To achieve this purpose the effect of a 24-hour exposure to 0–70 mM Piracetam on the growth of the L929 cell line and chick embryonic neurons in vitro was investigated. No statistically significant changes in cell viability or number was observed at 0–7 mM Piracetam in both cell types, although at 70 mM cell viability in the L929 cell line was significantly reduced when compared with the control. Initial studies indicate that Piacetam is only toxic at concentrations greater than 70 mM; however, the effects of repeated dosages over long periods still need to be investigated. [ABSTRACT FROM AUTHOR]

Especially in the field of memory encoding and retrieval, the results of functional neuroimaging have provided new insights in anatomico-functional interactions. In particular this holds true for the role of the prefrontal cortex in mnestic information processing, for the contribution and participation of the two hemispheres in various processes of information transmission, and for views on disturbed information processing after organically obvious and so-called psychogenic forms of memory impairments. This report particularly stresses the insights obtained by functional neuroimaging for probably environmentally triggered deficiencies in memory processing and discusses possible subtle neuroanatomical correlates of functional amnesias. It is especially emphasised that stress conditions and depressive states may modify the release of steroids (glucocorticoids) and transmitter agonists at the brain level with the consequence of selective memory disturbances which may manifest as a 'mnestic block syndrome'. [ABSTRACT FROM AUTHOR]