Neurotoxicity and Biomarkers of Lead Exposure: a Review

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies.Biomarkers are generally classified into three groups:biomarkers of exposure,effect,and susceptibility.The main body compartments that store lead are the blood,soft tissues,and bone;the half-life of lead in these tissues is measured in weeks for blood,months for soft tissues,and years for bone.Within the brain,lead-induced damage in the prefrontal cerebral cortex,hippocampus,and cerebellum can lead to a variety of neurological disorders,such as brain damage,mental retardation,behavioral problems,nerve damage,and possibly Alzheimer’s disease,Parkinson’s disease,and schizophrenia.This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Paul Tillich＇s Schizophrenia

Paul Tillich once confided to his secretary at Harvard that he was a schizophrenic. In this article, the author, who is also a schizophrenic, discusses symptoms of schizophrenia in Tillich＇s biography and theology. Tillich had always insisted that his theology was one of the kairos. By hiding his theological thought behind an arcane Greek word, Tillich dissimulated his own messiah complex. On several occasions, Tillich describes a mystical schizophrenic hallucination with such accuracy that it is obvious to those who have had similar visions that he was speaking from personal experience. This article raises unanswerable questions about the relationships between religious revelation, mystical ecstasy and schizophrenia.

Schizophrenia and Other Psychoses in Polish Middletown

The most of studies conducted up till now have shown a frequent occurrence of schizophrenia and other psychoses in cities compared to rural and suburban areas. The following research work was done on the basis of address data in a medium size town of people placed in psychiatric hospitals schizophrenia and other psychoses in the years 1989-2002. ICD9 criteria were initially used for hospital diagnosis, and then ICD10 criteria. To study the differences among particular districts of the town the test for two proportions was conducted. The analyzed group of persons amounted to 380 patients, including 169 men and 211 women. It indicated that patients more frequently lived in more urbanized and postindustrial districts of town as well as men aged 20-29 years old in postindustrial districts. It should be mentioned that more of patients placed the inner city, but also in postindustrial district and in districts with city housinz oroiects.

A selective reduction in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia patients

Objectives To determine the relative densities of the GABAergic subpopulation defined by calcium-binding proteins and to further study the importance of changes in GABAergic interneurons on neuropathology in the hippocampus in schizophrenia cases. Methods The relative densities and neuronal body size of cells immunoreactive for the calcium-binding proteins parvalbumin and calretinin as well as the area size of the hippocampal sub-fields were determined from the hippocampal tissue sections taken from schizophrenic patients and well-matched control subjects (15 per group). Results No significant difference in the density of calretinin-immunoreactive neurons and the neuronal body size of calretinin-positive neurons was found between subject groups. Relative to normal controls, schizophrenic patients showed a significant and profound deficit in the relative densities of parvalbumin-immunoreactive neurons in all hippocampal sub-fields. These reductions were more apparent in male schizophrenic patients and were unrelated to antipsychotic drug treatment, age or duration of illness. Conclusion The findings provide further evidence to support a profound and selective abnormality of a sub-population of GABAergic neurons in the hippocampus in schizophrenia cases, and are consistent with the etiological hypothesis of the neurodevelopment of schizophrenia.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase

Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in the central nervous system(CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter – nitric oxide(NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase(hi NOS) and enhanced the promoter activity of hi NOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

Schizophrenia:a classic battle ground of nature versus nurture debate

Much has been learned about the etiology and pathogenesis of schizophrenia since the term was first used by Eugene Bleuler over a century ago to describe one of the most important forms of major mental illness to affect mankind.Both nature and nurture feature prominently in our understanding of the genesis of the overall risk of developing schizophrenia.We now have a firm grasp of the broad structure of the genetic architecture and several key environmental risk factors have been identified and delineated.However,much of the heritability of schizophrenia remains unexplained and the reported environmental risk factors do not explain all the variances not attributable to genetic risk factors.The biggest problem at present is that our understanding of the causal mechanisms involved is still in its infancy.In this review,we describe the extent and limits of our knowledge of the specific genetic/constitutional and non-genetic/environmental factors that contribute to the overall risk of schizophrenia.We suggest novel methods may be required to understand the almost certainly immensely complex multi-level causal mechanisms that contribute to the generation of the schizophrenia phenotype.

BDNF rescues prefrontal dysfunction elicited by pyramidal neuron-specific DTNBP1 deletion in vivo

Dystrobrevin-binding protein 1 （Dtnbp1） is one of the earliest identified schizophrenia susceptibility genes. Reduced expression of DTNBP1 is commonly found in brain areas of schizophrenic patients. Dtnbp1-nuU mutant mice exhibit abnormalities in beha- viors and impairments in neuronal activities. However, how diminished DTNBP1 expression contributes to clinical relevant fea- tures of schizophrenia remains to be illustrated. Here, using a conditional Dtnbp1 knockout mouse line, we identified an in vivo schizophrenia-relevant function of DTNBP1 in pyramidal neurons of the medial prefrontal cortex （mPFC）. We demonstrated that DTNBP1 elimination specifically in pyramidal neurons of the mPFC impaired mouse pre-pu[se inhibition （PPI） behavior and reduced perisomatic GABAergic synapses. We further revealed that loss of DTNBP1 in pyramidal neurons diminished activity- dependent secretion of brain-derived neurotrophic factor （BDNF）. Finally, we showed that chronic BDNF infusion in the mPFC fully rescued both GABAergic synaptic dysfunction and PPI behavioral deficit induced by DTNBP1 elimination from pyramidal neurons. Our findings highlight brain region- and cell type-specific functions of DTNBP1 in the pathogenesis of schizophrenia, and under- score BDNF restoration as a potential therapeutic strategy for schizophrenia.

Schizophrenia risk-gene Crmp2 deficiency causes precocious critical period plasticity and deteriorated binocular vision

Brain-specific loss of a microtubule-binding protein collapsin response mediator protein-2(CRMP2)in the mouse recapitulates many schizophrenia-like behaviors of human patients,possibly resulting from associated developmental deficits in neuronal differentiation,path-finding,and synapse formation.However,it is still unclear how the Crmp2 loss affects neuronal circuit function and plasticity.By conducting in vivo and ex vivo electrophysiological recording in the mouse primary visual cortex(V1),we reveal that CRMP2 exerts a key regulation on the timing of postnatal critical period(CP)for experience-dependent circuit plasticity of sensory cortex.In the developing V1,the Crmp2 deficiency induces not only a delayed maturation of visual tuning functions but also a precocious CP for visual input-induced ocular dominance plasticity and its induction activity–coincident binocular inputs right after eye-opening.Mechanistically,the Crmp2 deficiency accelerates the maturation process of cortical inhibitory transmission and subsequently promotes an early emergence of balanced excitatory-inhibitory cortical circuits during the postnatal development.Moreover,the precocious CP plasticity results in deteriorated binocular depth perception in adulthood.Thus,these findings suggest that the Crmp2 deficiency dysregulates the timing of CP for experience-dependent refinement of circuit connections and further leads to impaired sensory perception in later life.