Volume 26, Issue 4

A growing body of evidence has linked two of the most common aged-related diseases: type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). It has led to the notion that drugs developed for the treatment of T2DM may be beneficial in modifying the pathophysiology of AD. As a receptor agonist of glucagon-like peptide-1 (GLP-1R), which is a newer drug class to treat T2DM, geniposide shows clear effects in inhibiting pathological processes underlying AD, such as promoting neurite outgrowth. In the present article, we review the possible molecular mechanisms of geniposide to protect the brain from pathologic damages underlying AD: reducing amyloid plaques, inhibiting τ phosphorylation, preventing memory impairment and loss of synapses, reducing oxidative stress and the chronic inflammatory response, and promoting neurite outgrowth via the GLP-1R signaling pathway. In summary, the Chinese herb geniposide shows great promise as a novel treatment for AD.

Autophagy is a vesicle and lysosome-mediated degradative pathway that is essential for protein homeostasis and cell health. In particular, compared to nonneuronal cells, neurons are dependent on high basal autophagy for survival. There is emerging agreement that defects in autophagy are likely to contribute to the neurodegenerative processes in numerous diseases, including Alzheimer’s disease (AD). Autophagy-lysosome defects occur early in the pathogenesis of AD and have been proposed to be a significant contributor to the disease process. Given the fact that autophagy deficits are likely major contributors to the etiology of AD, the focus of this review will be on recent studies that support a role for autophagy deficits in AD.

Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord’s normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

Toll-like receptors (TLRs) are important innate immune proteins, and the activation of the TLRs results in the activation of intracellular signaling pathways, leading to the expression of proinflammatory cytokines that are essential to the identification and clearance of invading pathogens. TLR signaling occurs through adaptor proteins, most commonly myeloid differentiation primary response gene 88 ( MyD88 ). It is now known that immune surveillance and inflammatory responses occur in neurodegenerative diseases and TLR/MYD88 signaling plays a critical role in these diseases. The included studies suggest a contribution for this signaling to the pathophysiology of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple system atrophy, and related disorders. In this review, a discussion of the recent findings in this field is presented.

Exposure to stressors elicits a spectrum of responses that span from potentially adaptive to maladaptive consequences at the structural, cellular and physiological level. These responses are particularly pronounced in the hippocampus where they also appear to influence hippocampal-dependent cognitive function and emotionality. The factors that influence the nature of stress-evoked consequences include the chronicity, severity, predictability and controllability of the stressors. In addition to adult-onset stress, early life stress also elicits a wide range of structural and functional responses, which often exhibit life-long persistence. However, the outcome of early stress exposure is often contingent on the environment experienced in adulthood, and could either aid in stress coping or could serve to enhance susceptibility to the negative consequences of adult stress. This review comprehensively examines the consequences of adult and early life stressors on the hippocampus, with a focus on their effects on neurogenesis, neuronal survival, structural and synaptic plasticity and hippocampal-dependent behaviors. Further, we discuss potential factors that may tip stress-evoked consequences from being potentially adaptive to largely maladaptive.

Leukemia inhibitory factor (LIF) is a multifunction cytokine that has various effects on different tissues and cell types in rodents and humans; however, its insufficiency has a relatively mild impact. This could explain why only some aspects of LIF activity are in the limelight, whereas other aspects are not well known. In this review, the LIF structure, signaling pathway, and primary roles in the development and function of an organism are reviewed, and the effects of LIF on stem cell growth and differentiation, which are important for its use in cell culturing, are described. The focus is on the roles of LIF in central nervous system development and on the modulation of its physiological functions as well as the involvement of LIF in the pathogenesis of brain diseases and injuries. Finally, LIF and its signaling pathway are discussed as potential targets of therapeutic interventions to influence both negative phenomena and regenerative processes following brain injury.

Response inhibition is a pivotal component of executive control, which is especially difficult to assess. Indeed, it is a substantial challenge to gauge brain-behavior relationships because this function is precisely intended to suppress overt measurable behaviors. A further complication is that no single neuroimaging method has been found that can disentangle the accurate time-course of concurrent excitatory and inhibitory mechanisms. Here, we argue that this objective can be achieved with electroencephalography (EEG) on some conditions. Based on a systematic review, we emphasize that the standard event-related potential N2 (N200) is not an appropriate marker of prepotent response inhibition. We provide guidelines for assessing the cortical brain dynamics of response inhibition with EEG. This includes the combined use of inseparable data processing steps (source separation, source localization, and single-trial and time-frequency analyses) as well as the amendment of the classical experimental designs to enable the recording of different kinds of electrophysiological activity predicted by different models of response inhibition. We conclude with an illustration based on recent findings of how fruitful this approach can be.

Iron deficiency (ID) is a major public health problem worldwide among children aged 0–12 months. Several factors seem to contribute to the iron-deficient state in infancy, including insufficient antenatal and neonatal iron supplementation, exclusive breastfeeding, and early umbilical cord clamping after birth. The most concerning complications of ID, except for anemia, are related to altered long-term neurodevelopment. Clinical studies have shown a negative impact of ID anemia on fetal and neonatal behavior including impairments of motor maturity, autonomic response, memory/learning, and mood. ID-induced defects during infancy seem to persist later in life, even after ID treatment. The underlying mechanisms involve dysfunctional myelination, neurotransmission alterations, and altered synaptogenesis and/or dendritogenesis. The purpose of the present review is to summarize these mechanisms and to provide recommendations for future clinical research in the field.