Volume 32, Issue 8

In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous vesicles secreted by various cells in the extracellular space. Accumulating evidence shows that EVs regulate cell-to-cell communication and signaling in the pathological processes of various diseases by carrying proteins, lipids, and nucleic acids to recipient cells. Glia-derived EVs act as a double-edged sword in the pathogenesis of central nervous system (CNS) diseases. They may be vectors for the spread of diseases or act as effective clearance systems to protect tissues. In this review, we summarize recent studies on glia-derived EVs with a focus on their relationships with CNS diseases.

The early secretory pathway, provisionally comprising of vesicular traffic between the endoplasmic reticulum (ER) and the Golgi apparatus, occurs constitutively in mammalian cells. Critical for a constant supply of secretory and plasma membrane (PM) materials, the pathway is presumably essential for general cellular function and survival. Neurons exhibit a high intensity in membrane dynamics and protein/lipid trafficking, with differential and polarized trafficking towards the somatodendritic and axonal PM domains. Mutations in genes encoding early secretory pathway membrane trafficking machinery components are known to result in neurodevelopmental or neurological disorders with disease manifestation in early life. Here, such rare disorders associated with autosomal recessive mutations in coat proteins, membrane tethering complexes and membrane fusion machineries responsible for trafficking in the early secretory pathway are summarily discussed. These mutations affected genes encoding subunits of coat protein complex I and II, subunits of transport protein particle (TRAPP) complexes, members of the YIP1 domain family (YIPF) and a SNAP receptor (SNARE) family member. Why the ubiquitously present and constitutively acting early secretory pathway machinery components could specifically affect neurodevelopment is addressed, with the plausible underlying disease etiologies and neuropathological mechanisms resulting from these mutations explored.

Huntington’s disease (HD) is a genetic, inexorably fatal neurodegenerative disease. Patient average survivability is up to 20 years after the onset of symptoms. Those who suffer from the disease manifest motor, cognitive, and psychiatric impairments. There is indirect evidence suggesting that omega-3 polyunsaturated fatty acids (ω-3 PUFA) could have alleviating effects on most of HD symptoms. These include beneficial effects against cachexia and weight loss, decrease of cognitive impairment over time, and improvement of psychiatric symptoms such as depression and irritability. Furthermore, there is a positive correlation between consumption of ω-3 PUFAs in diets and prevalence of HD, as well as direct effects on the disease via release of serotonin. Unfortunately, to date, very few studies have examined the effects of ω-3 PUFAs in HD, both on the symptoms and on disease progression. This paper reviews evidence in the literature suggesting that ω-3 PUFAs can be used in neurodegenerative disorders. This information can be extrapolated to support further research of ω-3 PUFAs and their potential use for HD treatment.

The ability to accurately recall locations and navigate our environment relies on multiple cognitive mechanisms. The behavioural and neural correlates of spatial navigation have been repeatedly examined using different types of mazes and tasks with animals. Accurate performances of many of these tasks have proven to depend on specific circuits and brain structures and some have become the standard test of memory in many disease models. With the introduction of virtual reality (VR) to neuroscience research, VR tasks have become a popular method of examining human spatial memory and navigation. However, the types of VR tasks used to examine navigation across laboratories appears to greatly differ, from open arena mazes and virtual towns to driving simulators. Here, we examined over 200 VR navigation papers, and found that the most popular task used is the virtual analogue of the Morris water maze (VWM). Although we highlight the many advantages of using the VWM task, there are also some major difficulties related to the widespread use of this behavioural method. Despite the task’s popularity, we demonstrate an inconsistency of use – particularly with respect to the environmental setup and procedures. Using different versions of the virtual water maze makes replication of findings and comparison of results across researchers very difficult. We suggest the need for protocol and design standardisation, alongside other difficulties that need to be addressed, if the virtual water maze is to become the ‘gold standard’ for human spatial research similar to its animal counterpart.