Volume 27, Issue 5

The lack of effective therapies for different neurodegenerative disorders has placed huge burdens on society. To overcome the restricted capacity of the central nervous system for regeneration, the promising alternative would be to use stem cells for more effective treatment of chronic degenerative and inflammatory neurological conditions and also of acute neuronal damage and from injuries or cerebrovascular diseases. The generation of induced pluripotent stem cells from somatic cells by the ectopic expression of specific transcription factors has provided the regenerative medicine field with a new tool for investigating and treating neurodegenerative diseases, including Alzheimer’s disease (AD). This technology provides an alternative to traditional approaches, such as nuclear transfer and somatic cell fusion using embryonic stem cells. However, due to a problem in standardization of certain reprogramming techniques and systems research, the induced pluripotent stem cell-based technology is still in its infancy. The present paper is aimed at a brief review of the current status in modeling and cell-based therapies for AD.

Hemispheric asymmetries are a central principle of nervous system architecture and shape the functional organization of most cognitive systems. Structural gray matter asymmetries and callosal interactions have been identified as contributing neural factors but always fell short to constitute a full explanans. Meanwhile, recent advances in in vivo white matter tractography have unrevealed the asymmetrical organization of many intrahemispheric white matter pathways, which might serve as the missing link to explain the substrate of functional lateralization. By taking into account callosal interactions, gray matter asymmetries and asymmetrical interhemispheric pathways, we opt for a new triadic model that has the potential to explain many observations which cannot be elucidated within the current frameworks of lateralized cognition.

It is well known that synaptic plasticity is the cellular mechanism underlying learning and memory. Activity-dependent synaptic changes in electrical properties and morphology, including synaptogenesis, lead to alterations of synaptic strength, which is associated with long-term potentiation (LTP). Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling is involved in learning and memory formation by regulating synaptic plasticity. The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is one of the key signaling cascades downstream BDNF/TrkB and is believed to modulate N -methyl- d -aspartate (NMDA) receptor-mediated synaptic plasticity. However, the molecular mechanism underlying the connection between these two key players in synaptic plasticity remains largely unknown. Girders of actin filament (Girdin), an Akt substrate that directly binds to actin filaments, has been shown to play a role in neuronal migration and neuronal development. Recently, we identified Girdin as a key molecule involved in regulating long-term memory. It was demonstrated that phosphorylation of Girdin by Akt contributed to the maintenance of LTP by linking the BDNF/TrkB signaling pathway with NMDA receptor activity. These findings indicate that Girdin plays a pivotal role in a variety of processes in the CNS. Here, we review recent advances in our understanding about the roles of Girdin in the CNS and focus particularly on neuronal migration and memory.

Neural stem cell transplantation is becoming a promising and attractive cell-based treatment modality for repairing the damaged central nervous system. One of the limitations of this approach is that the proportion of functional cells differentiated from stem cells still remains at a low level. In recent years, novel long non-coding RNAs (lncRNAs) are being discovered at a growing pace, suggesting that this class of molecules may act as novel regulators in neuronal-glial fate specification. In this review, we first describe the general features of lncRNAs that are more likely to be relevant to reveal their function. By this, we aim to point out the specific roles of a number of lncRNAs whose function has been described during neuronal and glial cell differentiation. There is no doubt that investigation of the lncRNAs will open a new window in studying neuronal-glial fate specification.

Stroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future.

Spinal reflex excitability is traditionally assessed to investigate neural adjustments that occur during human movement. Different experimental procedures are known to condition spinal reflex excitability. Among these, lengthening movements and static stretching the human triceps have been investigated over the last 50 years. The purpose of this review is to shed light on several apparent incongruities in terms of magnitude and duration of the reported results. In the present review dissimilarities in neuro-spinal changes are examined in relation to the methodologies applied to condition and measure them. Literature that investigated three different conditioning procedures was reviewed: passive dorsiflexion, active dorsiflexion through antagonists shortening and eccentric plantar-flexors contractions. Measurements were obtained before, during and after lengthening or stretching. Stimulation intensities and time delays between conditioning procedures and stimuli varied considerably. H-reflex decreases immediately as static stretching is applied and in proportion to the stretch degree. During dorsiflexions the inhibition is stronger with greater dorsiflexion angular velocity and at lower nerve stimulation intensities, while it is weaker if any concomitant muscle contraction is performed. Within 2 s after a single passive dorsiflexion movement, H-reflex is strongly inhibited, and this effect disappears within 15 s. Dorsiflexions repeated over 1 h and prolonged static stretching training induce long-lasting inhibition. This review highlights that the apparent disagreement between studies is ascribable to small methodological differences. Lengthening movements and stretching can strongly influence spinal neural pathways. Results interpretation, however, needs careful consideration of the methodology applied.

It is estimated that approximately 0.5%–3% of fetuses are prenatally exposed to cocaine (COC). The neurodevelopmental implications of this exposure are numerous and include motor skill impairments, alterations of social function, predisposition to anxiety, and memory function and attention deficits; these implications are commonly observed in experimental studies and ultimately affect both learning and IQ. According to previous studies, the clinical manifestations of prenatal COC exposure seem to persist at least until adolescence. The pathophysiological cellular processes that underlie these impairments include dysfunctional myelination, disrupted dendritic architecture, and synaptic alterations. On a molecular level, various neurotransmitters such as serotonin, dopamine, catecholamines, and γ-aminobutyric acid seem to participate in this process. Finally, prenatal COC abuse has been also associated with functional changes in the hormones of the hypothalamic-pituitary-adrenal axis that mediate neuroendocrine responses. The purpose of this review is to summarize the neurodevelopmental consequences of prenatal COC abuse, to describe the pathophysiological pathways that underlie these consequences, and to provide implications for future research in the field.

Parkinson’s disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (tremor, bradykinesia/akinesia, and rigidity), PD patients also show other motor deficits, including gait disturbance, speech deficits, and impaired handwriting. However, along with these key motor symptoms, PD patients also experience cognitive deficits in attention, executive function, working memory, and learning. Recent evidence suggests that these motor and cognitive deficits of PD are not completely dissociable, as aspects of cognitive dysfunction can impact motor performance in PD. In this article, we provide a review of behavioral and neural studies on the associations between motor symptoms and cognitive deficits in PD, specifically akinesia/bradykinesia, tremor, gait, handwriting, precision grip, and speech production. This review paves the way for providing a framework for understanding how treatment of cognitive dysfunction, for example cognitive rehabilitation programs, may in turn influence the motor symptoms of PD.

Postural instability (PI) is one of the most debilitating motor symptoms of Parkinson’s disease (PD), as it is associated with an increased risk of falls and subsequent medical complications (e.g. fractures), fear of falling, decreased mobility, self-restricted physical activity, social isolation, and decreased quality of life. The pathophysiological mechanisms underlying PI in PD remain elusive. This short review provides a critical summary of the literature on PI in PD, covering the clinical features, the neural and cognitive substrates, and the effects of dopaminergic medications and deep brain stimulation. The delayed effect of dopaminergic medication combined with the success of extrastriatal deep brain stimulation suggests that PI involves neurotransmitter systems other than dopamine and brain regions extending beyond the basal ganglia, further challenging the traditional view of PD as a predominantly single-system neurodegenerative disease.