Volume 25, Issue 5

Reward seeking is controlled by conditioned stimuli (CSs). There is a positive relation between mesocorticolimbic dopamine (DA) and the performance of learned reward-directed behavior. The mechanisms by which reward-, including drug-, associated stimuli come to acquire the capacity to activate the DA systems are not fully understood. In this review, we discuss the possible neurochemical mechanisms within the ventral tegmental area that may be involved in how CSs acquire the capacity to activate ventral tegmental area (VTA) DA neurons based on principles of long-term potentiation in the VTA and the role of mesocorticolimbic DA in reward-related learning. We propose that CSs function as such because they acquire the capacity to activate VTA DA neurons. Furthermore, CSs come to acquire this control of VTA DA cells when there is coincident N -methyl- d -aspartate receptor stimulation on VTA DA cells and strong depolarization of VTA DA cells, possibly by muscarinic acetylcholine receptor stimulation on these cells. This coincident activity leads to the strengthening of CS-associated glutamatergic synapses and the control by CSs of mesocorticolimbic DA systems and reward-directed behavior.

Fetal alcohol spectrum disorder (FASD) is one of the main causes of mental retardation worldwide. Nearly 1% of children in North America are affected from antenatal exposure to ethanol. Its economic burden in industrialized countries is increasing. It is estimated that, in the United States, 4.0 billion dollars are annually expended in the treatment and rehabilitation of these patients. As a pathologic entity, they present with a broad symptomatology. Fetal alcohol syndrome (FAS) is the most readily recognized clinical manifestation of these disorders. Various factors seem to contribute in the pathogenesis of FASD-related cognitive disorders. During the last 20 years, several potential pretranslational and posttranslational factors have been extensively studied in various experimental animal models. Research has specifically focused on several neurotransmitters, insulin resistance, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, abnormal glycosylation of several proteins, oxidative stress, nutritional antioxidants, and various epigenetic factors. The purpose of the present review is to summarize the clinical manifestations of this disorder during childhood and adolescence and to summarize the possible pathophysiologic and epigenetic pathways that have been implicated in the pathophysiology of FASD.

Hereditary cerebral hemorrhage with amyloidosis – Dutch type is an autosomal dominant hereditary disease caused by a point mutation in the amyloid precursor protein gene on chromosome 21. The mutation causes an amino acid substitution at codon 693 (E22Q), the ‘Dutch mutation’. Amyloid β, the product after cleavage of the amyloid precursor protein, is secreted into the extracellular space. The Dutch mutation leads to altered amyloid β cleavage and secretion, enhanced aggregation properties, higher proteolysis resistance, lowered brain efflux transporter affinity, and enhanced cell surfaces binding. All these result in amyloid β accumulation in cerebral vessel walls, causing cell death and vessel wall integrity loss, making cerebral vessel walls in hereditary cerebral hemorrhage with amyloidosis-Dutch type more prone to rupture and obstruction, leading to hemorrhages and infarcts. Studying the effects of altered amyloid β metabolism due to mutations like the ‘Dutch’ provides us with a better understanding of amyloid β toxicity, also in other amyloid β diseases like sporadic cerebral amyloid angiopathy and Alzheimer’s disease.

Multiple system atrophy (MSA) is a neurodegenerative disease that presents as an autonomic dysfunction in combination with varying degrees of parkinsonism and cerebellar ataxia. It comprises a pathologically widespread neuronal loss accompanied by gliosis in the basal ganglia, cerebellum, pons, inferior olivary nuclei, and spinal cord. As a rapidly progressive disorder, MSA develops with autonomic dysfunction and mobility problems in several years. These autonomic and motor function impairments severely disrupt the patients’ daily lives. Currently, the therapeutic management of this disease is only symptomatic. An early and accurate diagnosis is helpful not only in the clinical field but also in the research for new therapies. The biomarkers in cerebrospinal fluid (CSF) and serum facilitate the differential diagnosis of MSA when the disease is difficult to recognize based on the clinical features or even presymptomatic. This review will summarize the biomarkers present in CSF that are potential candidates to accurately differentiate MSA from other similar neurodegenerative disorders.

The development of new molecular imaging techniques has bridged the gap between preclinical and clinical research. During the last decade, the developments in imaging strategies have taken a great leap by the advancements in new imaging scanners, development of pharmaceutical drugs, diagnostic agents, and new therapeutic regimens that made significant improvements in health care. The knowledge gained from imaging techniques in preclinical research can be applicable to the patients. Similarly, the problems from clinical studies with humans can be tested and studied in preclinical studies. The appropriate application of molecular imaging to drug discovery and development can markedly reduce costs and the time required for new drug development. Some imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI), reveal anatomical images, and single-photon emission computed tomography (SPECT), SPECT/positron emission tomography (PET), and PET show functional images. These developing molecular or neuroimaging methods provide increasingly detailed structural and functional information about the nervous system. The basic principles of each technique are described followed by examples of the current applications to cutting-edge neuroscience research. In summary, it is shown that neuroimaging continues to grow and evolve, embracing new technologies and advancing to address ever more complex and important neuroscience questions.

During early and late embryo neurodevelopment, a large number of molecules work together in a spatial and temporal manner to ensure the adequate formation of an organism. Diverse signals participate in embryo patterning and organization synchronized by time and space. Among the molecules that are expressed in a temporal and spatial manner, and that are considered essential in several developmental processes, are the microRNAs (miRNAs). In this review, we highlight some important aspects of the biogenesis and function of miRNAs as well as their participation in ectoderm commitment and their role in central nervous system (CNS) development. Instead of giving an extensive list of miRNAs involved in these processes, we only mention those miRNAs that are the most studied during the development of the CNS as well as the most likely mRNA targets for each miRNA and its protein functions.

The ability to maintain balance is critical for daily activities such as walking and fall avoidance. The contemporary models of postural control emphasize the central and somatic interactions engaged in maintaining balance; however, there is emerging evidence that the autonomic nervous system (ANS) – the sympathetic division, in particular – routinely participates in postural control. The purpose of this paper is to review the evidence demonstrating the autonomic interactions in postural control. These interactions are presented in two broad categories: those that conceptualize the maintenance of postural equilibrium as a component of bodily homeostasis and those that illustrate how changes in affective states link cognitive perceptions and physiological responses (in this case, balance). The shared commonalities between postural and autonomic pathways are presented, pointing to the areas of overlap and the potential sources of the interaction. Although the specific function of autonomic engagement in postural control remains unknown, the potential roles are explored and highlight the directions for continued study.

Toll-like receptors (TLRs) recognizing the exogenous pathogen-associated molecular patterns (PAMPs) are part of the innate immune system that plays a role in various challenging interactions between the neurons and the immune system. Stroke as a major injury to the central nervous system (CNS) is one of the hot points of such cross-talk. The various roles of the different types of TLRs in stroke can be classified into three major categories: (1) the hazardous effect of TLRs with a focus on the part in poststroke neurodegeneration, (2) the beneficial effect of those types of TLRs that exert a neuroprotective effect following an ischemic insult, and (3) the role of TLRs in immunomodulation on one hand and the possible autoimmunity as a consequence of neuronal injury due to an ischemic attack on the other hand. However, the mentioned functions of TLRs, similar to many other parts of the immune system, might overlap in many aspects. The current review article, including both experimental and clinical studies, is an attempt to bring together the studies that have investigated the roles of TLRs in stroke while referring to the apparent controversies in this field, with pointing out the new ideas for further considerations.

The interaction between the immune and nervous systems suggests invaluable mechanisms for several pathological conditions, especially neurodegenerative disorders. Multiple sclerosis (MS) is a potentially disabling chronic autoimmune disease, characterized by chronic inflammation and neurodegenerative pathology of the central nervous system. Toll-like receptors (TLRs) are an important family of receptors involved in host defense and in recognition of invading pathogens. The role of TLRs in the pathogenesis of autoimmune disorders such as MS is only starting to be uncovered. Recent studies suggest an ameliorative role of TLR3 and a detrimental role of other TLRs in the onset and progression of MS and experimental autoimmune encephalomyelitis, a murine model of MS. Thus, modulating TLRs can represent an innovative immunotherapeutic approach in MS therapy. This article outlines the role of these TLRs in MS, also discussing TLR-targeted agonist or antagonists that could be used in the different stages of the disease.