Volume 2, Issue 4

Major depressive disorder (MDD) is a pervasive and debilitating illness, with a recurrent course and chronic prognosis. Although effective treatments for MDD exist, there is a pressing need to characterize relapse vulnerability in order to design effective prophylactic care. To date, heterogeneity within depression neuroimaging research has made it difficult to establish a reliable biomarker of disorder susceptibility. In this paper, we review neuroimaging evidence for the assessment of MDD vulnerability, theorizing that current findings can be broadly distinguished between those indicating the presence of depressive episodes and those indicating MDD vulnerability during symptom remission. We argue that unlike the amygdala hyperactivity and prefrontal hypoactivity observed during MDD episodes, prefrontal hyperactivity may be a characteristic of dysphoric cognition during symptom remission that indicates MDD vulnerability and relapse risk. Drawing on current research of normative emotion regulation, we describe a potential test of MDD vulnerability, employing emotional challenge paradigms that induce cognitive reactivity — the increased endorsement of negative self-descriptions during a transient dysphoric mood. Relative to a normative model of prefrontal function, the neuroimaging assessment of cognitive reactivity may provide a reliable indicator of MDD vulnerability, advancing the field of biomarker research as well as the delivery of preventative treatment on an individual basis.

The olfactory system represents a perfect model to study the interactions between the central and peripheral nervous systems in order to establish a neural circuit during early embryonic development. In addition, another important feature of this system is the capability to integrate new cells generated in two neurogenic zones: the olfactory epithelium in the periphery and the wall of the lateral ventricles in the CNS, both during development and adulthood. In all these processes the combination and sequence of specific molecular signals plays a critical role in the wiring of the olfactory axons, as well as the precise location of the incoming cell populations to the olfactory bulb. The purpose of this review is to summarize recent insights into the cellular and molecular events that dictate cell settling position and axonal trajectories from their origin in the olfactory placode to the formation of synapses in the olfactory bulb to ensure rapid and reliable transmission of olfactory information from the nose to the brain.

Microglia are resident hematopoietic cells that play important roles in the damaged or degenerating adult nervous system. Microglia are involved in neuropathogenesis of various diseases. Microglia are also essential for neuroprotection and comprise an essential component of the neural stem cell niche. The activation of microglia is an important phenomenon associated with several neurological disorders that arise from infections to developmental abnormalities and behavioral pathologies. Noonan syndrome (NS) is associated with mutations in the PTPN11 gene and also accounts for mental retardation in children. Interestingly, in mouse models of NS, mutations in the PTPN11 gene resulted in dysregulation of neural progenitors. The present study describes the activation of microglia in the NS mouse model, which results in an inflammatory phenotype with expression of IL-1b and defective phagocytosis. To test whether microglia from NS mice are important for neural precursor maintenance or self-renewal, embryonic neural precursors from the cortex of WT mice were cultured. Microglia from NS and WT mice were then added to cortical precursor cells which showed that microglia from NS mice inhibited astrogenesis. Together, these results demonstrate that microglia can dysregulate neural precursor development in NS, and suggest that alterations in microglial number as a consequence of genetic or pathological events may perturb neural development by directly affecting embryonic neural precursors.

Stem cells have long been in focus as potential therapy or even cure for a whole myriad of diseases. Many neurodegenerative disorders, both acute and chronic, are characterized by irreversible neuronal damage and loss, and only a few efficient treatment options exist. In contrast to many other tissues, the potential of self-regeneration of the central nervous system is highly limited. There is hope that stem cells could replace the damaged neuronal and glial cells, and provide biological and functional restoration based on their properties of self renewal and the ability to give rise to different cells. In recent years, the promising results of research on animal models has led to the establishment of the first clinical trials; although no clear evidence of therapeutic benefit for any of the conditions have been ascertained. Here we give a review of the current strategies of stem-cell based therapy for some of the more common neurological disorders, discussing the progress and current challenges, and giving an overview of future perspectives.

Glioblastoma Multiforme (GBM) is the most malignant and devastating primary brain tumour with a median survival of ∼12–16 months. Although recent large scale sequencing projects have shed considerable light into the complexity of the disease, there remains much to be elucidated in the hopes of generating effective therapeutic strategies. Although these studies investigate the mutations and expression of bulk tumour they have limits with respect to cell of origin and the concept of brain tumour initiating cells (BTIC). Current research has challenged the old paradigm of the stochastic model as recent evidence suggests that a subset of cancer cells within a tumor is responsible for tumor initiation, maintenance, and resistance to therapy. To gain a better understanding of the different compartment of cells that GBM comprise of require careful and elegant experiments. In addition to studying GBM, exploring the role of normal neural stem cells and progenitors cells is essential to partially explain whether these GBM BTIC behave similarly or differently then their non transformed counterparts. Here we discuss the recent literature between the two models, candidate regions of glioma genesis, candidate cells of origin for GBM, and possible therapeutic avenues to explore.

Gene expression was investigated in the major brain subdivisions (telencephalon, diencephalon, midbrain and hindbrain) in a representative reptile, Alligator mississipiensis, during the later stages of embryonic development. The following genes were examined: voltage-gated sodium channel isoforms: NaV1.1 and NaV1.2; synaptic vesicle 2a (SV2a); synaptophysin; and calbindin 2. With the exception of synaptophysin, which was only expressed in the telencephalon, all genes were expressed in all brain regions sampled at the time periods examined. For NaV1.1, gene expression varied according to brain area sampled. When compared with NaV1.1, the pattern of NaV1.2 gene expression differed appreciably. The gene expression of SV2a was the most robust of any of the genes examined. Of the other genes examined, although differences were noted, no statistically significant changes were found either between brain part or time interval. Although limited, the present analysis is the first quantitative mRNA gene expression study in any reptile during development. Together with future experiments of a similar nature, the present gene expression results should determine which genes are expressed in major brain areas at which times during development in Alligator. When compared with other amniotes, these results will prove useful for determining how gene expression during development influences adult brain structure.

Neuroprotection is a therapeutic strategy that attempts to save neurons from irreversible injury by modifying the effects of the ischemic cascade or facilitating reperfusion. Although numerous agents have shown neuroprotective effect in preclinical trials, their translation to clinical trials failed to show any meaningful effect. The Stroke Therapy Academic Industry Roundtable (STAIR) guidelines were made for performing research on neuroprotective agents in pre-clinical and clinical trials. Although the STAIR guidelines have been available for more than ten years, we still do not have any adequate neuroprotective agents. Reasons for unsuccessful translation from preclinical to clinical research can be considered along stages of drug development: 1) preclinical, 2) transitional and 3) clinical. By extending the therapeutic window for application of intravenous thrombolysis in acute stroke patients to 4.5 hours, as well as increasing the use intra-arterial thrombolysis and development of mechanical devices for thrombectomy in 6 hour period we may be able to achieve some degree of neuroprotection in acute stroke. Future therapy is likely to add to the current thrombolytic therapy with potential neuroprotective drugs or procedures.

Multiple sclerosis (MS) is a debilitating disease that affects millions. There is no known cure for the disease and neither is the cause of the disease known. Recent studies have indicated that it is a multi-factorial disease with several genes involved. Importantly, sunlight and vitamin D have been implicated in the progression of the disease. The pathogenesis of MS chiefly involves loss of oligodendrocytes, which in addition to being killed by inflammatory mediators in the CNS, also succumbs to loss of trophic support from astrocytes. Neurotrophins play an important role in myelination and the cellular prion protein (PrPC) is a key player in this process. Although the physiological roles of PrPC remain to be fully understood, increasing evidence suggests multiple roles for PrPC in regulation of cellular immunity and for its interaction with several neurotrophins that are necessary for homeostasis of the nervous system. This mini-review focuses on the findings establishing a crucial role for PrPC in the neuropathogenesis of MS, emphasizing its neuroprotective role. Since MS is a multi-factorial disease with unknown etiology and no cure, this review aims to highlight endogenous repair mechanisms mediated by PrPC that might contribute to functional recovery in MS patients.

Young-onset dementia (before age of 65) is relatively infrequent and presents a challenge in everyday neurological practice due to wide spectrum of clinical presentations and diversity of underlying etiology. When cognitive deficits are accompanied with liver dysfunction different etiologies should be considered. We present a case report of a young patient with subclinical decompensated liver disease due to underlying chronic hepatitis C, presented with the mildest form of hepatic encephalopathy spectrum, called minimal (subclinical) hepatic encephalopathy and characteristic MRI changes.