Neuroscience
-
Individuals are exposed to stressful events in their daily life. The effects of stress on brain function ranges from highly adaptive to increasing the risk to develop psychopathology. For example, stressful experiences are remembered well which can be seen as a highly appropriate behavioral adaptation. ⋯ An important question that remains to be addressed is how stress regulates brain function and what determines the threshold between adaptive and maladaptive responses. Excitatory synapses play a crucial role in synaptic transmission, synaptic plasticity and behavioral adaptation. In this review we discuss how brief and prolonged exposure to stress, in adulthood and early life, regulate the function of these synapses, and how these effects may contribute to behavioral adaptation and psychopathology.
-
Withdrawal from opiates, such as heroin or oral narcotics, is characterized by a host of aversive physical and emotional symptoms. High rates of relapse and limited treatment success rates for opiate addiction have prompted a search for new approaches. For many opiate addicts, achieving abstinence may be further complicated by poly-drug use and co-morbid mental disorders. ⋯ This review will summarize the literature surrounding the molecular effects of cannabinoids and opioids on the locus coeruleus-norepinephrine system, a key circuit implicated in the negative sequelae of opiate addiction. A consideration of the trends and effects of marijuana use in those seeking treatment to abstain from opiates in the clinical setting will also be presented. In summary, the present review details how cannabinoid-opioid interactions may inform novel interventions in the management of opiate dependence and withdrawal.
-
Review
Prenatal ontogeny as a susceptibility period for cortical GABA neuron disturbances in schizophrenia.
Cognitive deficits in schizophrenia have been linked to disturbances in GABA neurons in the prefrontal cortex (PFC). Furthermore, cognitive deficits in schizophrenia appear well before the onset of psychosis and have been reported to be present during early childhood and even during the first year of life. Taken together, these data raise the following question: Does the disease process that produces abnormalities in prefrontal GABA neurons in schizophrenia begin prenatally and disrupt the ontogeny of cortical GABA neurons? Here, we address this question through a consideration of evidence that genetic and/or environmental insults that occur during gestation initiate a pathogenetic process that alters cortical GABA neuron ontogeny and produces the pattern of GABA neuron abnormalities, and consequently cognitive difficulties, seen in schizophrenia. ⋯ Third, we discuss recent studies demonstrating altered expression of these ontogenetic factors in the PFC in schizophrenia. Fourth, we discuss the potential role of disturbances in the maternal-fetal environment such as maternal immune activation in the development of GABA neuron dysfunction. Finally, we propose critical questions that need to be answered in future research to further investigate the role of altered GABA neuron ontogeny in the pathogenesis of schizophrenia.
-
The regulation of D₃ receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D₃-preferring radioligand [(3)H]WC-10 and a D₂-preferring radioligand [(3)H]raclopride were used and the absolute densities of the dopamine D₃ and D₂ receptors were determined in the striatal regions and substantia nigra (SN) from postmortem brains from five cases of DLBD, which included dementia with Lewy bodies (DLB, n=4) and Parkinson disease dementia (PDD, n=1). The densities of the dopamine D₁ receptor, vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT) were also measured by quantitative autoradiography using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively. ⋯ VMAT2 and DAT densities were reduced in all the brain regions measured in DLB/PDD, however, the significant reduction was found in the putamen for DAT and in the NAc and SN for VMAT2. The decrease of dopamine pre-synaptic markers implies neuronal loss in the substantia nigra pars compacta (SNpc) in these DLB/PDD cases, while the increase of D₃ receptors in striatal regions could be attributed to dopaminergic medication history and psychiatric states such as hallucinations. Whether it also reflects compensatory regulation upon dopaminergic denervation warrants further confirmations on larger populations.
-
Nuclear factor (NF)-κB acetylation has been shown to participate in a number of neurological processes by regulating the expression of certain genes. We have previously demonstrated the neuronal nitric oxide synthase (nNOS) expression and nitric oxide (NO) production may be regulated by NF-κB acetylation via an NF-κB responsive element within the nNOS promoter in neuronal cells. p300 is a ubiquitous transcription coactivator with intrinsic histone acetyltransferase (HAT) activity, which is important in the nervous system. ⋯ Meanwhile, p300 was shown to directly acetylate NF-κB p65 and p50 subunits, interact with NF-κB and bind to the NF-κB responsive element region within the nNOS promoter. Taken together, our results indicate p300 acts as both an HAT and a coactivator in regulating NF-κB-mediated nNOS expression, which provide some correlations between p300 and nNOS in neuronal cell, and suggest that some p300-related neurological disorders may be partially based on its effect on the nNOS expression.