Volume 27, Issue 8

The cerebellar cholinergic system belongs to the third type of afferent nerve fiber system (after the climbing and mossy fibers), and has important modulatory effects on cerebellar circuits and cerebellar-mediated functions. In this report, we review the cerebellar cholinergic system, including cholinergic origins and innervations, acetylcholine receptor expression and distributions, cholinergic modulations of neuronal firing and synaptic plasticity, the cholinergic role in cerebellar-mediated integral functions, and cholinergic changes during development and aging. Because some motor and mental disorders, such as cerebellar ataxia and autism, are accompanied with cerebellar cholinergic disorders, we also discuss the correlations between cerebellar cholinergic dysfunctions and these disorders. The cerebellar cholinergic input plays an important role in the modulation of cerebellar functions; therefore, cholinergic abnormalities could induce physiological dysfunctions.

The prevalence of mental diseases, especially neurodegenerative disorders, is ever-increasing, while treatment options for such disorders are limited and insufficient. In this scarcity of available medication, it is a feasible strategy to search for potential drugs among natural compounds, such as those found in plants. One such plant source is the root of Chinese sage, Salvia miltiorrhiza Bunge (Labiatae), which contains several compounds reported to possess neuroprotective activities. The most important of these compounds are tanshinones, which have been reported to possess ameliorative activity against a myriad of mental diseases such as Alzheimer’s disease, cerebral ischemia/reperfusion injury, and glioma, along with promoting neuronal differentiation and manifesting antinociceptive and anticonvulsant outcomes. This review offers a critical evaluation of the utility of tanshinones to treat mental illnesses, and sheds light on the underlying mechanisms through which these naturally occurring compounds confer neuroprotection.

In early- or late-onset Alzheimer’s disease (AD), inflammation, which is triggered by pathologic conditions, influences the progression of neurodegeneration. Brain-derived neurotrophic factor (BDNF) has emerged as a crucial mediator of neurogenesis, because it exhibits a remarkable activity-dependent regulation of expression, which suggests that it may link inflammation to neurogenesis. Emerging evidence suggests that acute and chronic inflammation in AD differentially modulates neurotrophin functions, which are related to the roles of inflammation in neuroprotection and neurodegeneration. Recent studies also indicate novel mechanisms of BDNF-mediated neuroprotection, including the modulation of autophagy. Numerous research studies have demonstrated reverse parallel alterations between proinflammatory cytokines and BDNF during neurodegeneration; thus, we hypothesize that one mechanism that underlies the negative impact of chronic inflammation on neurogenesis is the reduction of BDNF production and function by proinflammatory cytokines.

Alzheimer’s disease (AD) is the most prevalent cause of dementia in the aging population worldwide. SIRT1 deacetylation of histones and transcription factors impinge on multiple neuronal and non-neuronal targets, and modulates stress response, energy metabolism and cellular senescence/death pathways. Collectively, SIRT1 activity could potentially affect multiple aspects of hippocampal and cortical neuron function and survival, thus modifying disease onset and progression. In this review, the known and potential mechanisms of action of SIRT1 with regard to AD, and its potential as a therapeutic target, are discussed.

Contemporary theories for the aetiology of borderline personality disorder (BPD) take a lifespan approach asserting that inborn biological predisposition is potentiated across development by environmental risk factors. In this review, we present and critically evaluate evidence on the neurobiology of BPD in childhood and adolescence, compare this evidence to the adult literature, and contextualise within a neurodevelopmental framework. A systematic review was conducted to identify studies examining the neurobiological (i.e. genetic, structural neuroimaging, neurophysiological, and neuropsychological) correlates of BPD symptoms in children and adolescents aged 19 years or under. We identified, quality assessed, and narratively summarised 34 studies published between 1980 and June 2016. Similar to findings in adult populations, twin studies indicated moderate to high levels of heritability of BPD, and there was some evidence for gene-environment interactions. Also consistent with adult reports is that some adolescents with BPD demonstrated structural (grey and white matter) alterations in frontolimbic regions and neuropsychological abnormalities (i.e. reduced executive function and disturbances in social cognition). These findings suggest that neurobiological abnormalities observed in adult BPD may not solely be the consequence of chronic morbidity or prolonged medication use. They also provide tentative support for neurodevelopmental theories of BPD by demonstrating that neurobiological markers may be observed from childhood onwards and interact with environmental factors to increase risk of BPD in young populations. Prospective studies with a range of repeated measures are now required to elucidate the temporal unfurling of neurobiological features and further delineate the complex pathways to BPD.

In 2008, using a model of compression brain ischemia, we presented the first evidence that mitochondria-targeted antioxidants of the SkQ family, i.e. SkQR1 [10-(6′-plastoquinonyl)decylrhodamine], have a neuroprotective action. It was shown that intraperitoneal injections of SkQR1 (0.5–1 μmol/kg) 1 day before ischemia significantly decreased the damaged brain area. Later, we studied in more detail the anti-ischemic action of this antioxidant in a model of experimental focal ischemia provoked by unilateral intravascular occlusion of the middle cerebral artery. The neuroprotective action of SkQ family compounds (SkQR1, SkQ1, SkQTR1, SkQT1) was manifested through the decrease in trauma-induced neurological deficit in animals and prevention of amyloid-β-induced impairment of long-term potentiation in rat hippocampal slices. At present, most neurophysiologists suppose that long-term potentiation underlies cellular mechanisms of memory and learning. They consider inhibition of this process by amyloid-β 1-42 as an in vitro model of memory disturbance in Alzheimer’s disease. Further development of the above studies revealed that mitochondria-targeted antioxidants could retard accumulation of hyperphosphorylated τ-protein, as well as amyloid-β 1-42 , and its precursor APP in the brain, which are involved in developing neurodegenerative processes in Alzheimer’s disease.

Alzheimer’s disease (AD) is a common health problem in elderly people. There has been considerable research toward the diagnosis and early detection of this disease in the past decade. The sensitivity of biomarkers and the accuracy of the detection techniques have been defined to be the key to an accurate diagnosis. This paper presents a state-of-the-art review of the research performed on the diagnosis of AD based on imaging and machine learning techniques. Different segmentation and machine learning techniques used for the diagnosis of AD are reviewed including thresholding, supervised and unsupervised learning, probabilistic techniques, Atlas-based approaches, and fusion of different image modalities. More recent and powerful classification techniques such as the enhanced probabilistic neural network of Ahmadlou and Adeli should be investigated with the goal of improving the diagnosis accuracy. A combination of different image modalities can help improve the diagnosis accuracy rate. Research is needed on the combination of modalities to discover multi-modal biomarkers.

In recent years, there has been considerable research interest in the study of brain connectivity using the resting state functional magnetic resonance imaging (rsfMRI). Studies have explored the brain networks and connection between different brain regions. These studies have revealed interesting new findings about the brain mapping as well as important new insights in the overall organization of functional communication in the brain network. In this paper, after a general discussion of brain networks and connectivity imaging, the brain connectivity and resting state networks are described with a focus on rsfMRI imaging in stroke studies. Then, techniques for preprocessing of the rsfMRI for stroke patients are reviewed, followed by brain connectivity processing techniques. Recent research on brain connectivity using rsfMRI is reviewed with an emphasis on stroke studies. The authors hope this paper generates further interest in this emerging area of computational neuroscience with potential applications in rehabilitation of stroke patients.