scholarly journals Glial pathology in neuropsychiatric disorders: a brief review

Author(s):  
Shilpa Borehalli Mayegowda ◽  
Christofer Thomas

Abstract Neurons have been considered the major functional entities of the nervous system that are responsible for most of the functions even though glial cells largely outnumber them. However, recent reports have proved that glial cells do not function just like glue in the nervous system but also substantially affect neuronal function and activities, and are significantly involved in the underlying pathobiology of various psychiatric disorders. Dysfunctional astrocytes and degeneration of glial cells are postulated to be critical factors contributing to the aggravation of depressive-like symptoms in humans, which was proved using animal models. Alteration in glial cell function predominantly targets three main brain regions – the prefrontal cortex, limbic areas including the hippocampus, and the amygdala, which have been extensively studied by various researchers across the globe. These studies have postulated that failure in adopting to the changing neurophysiology due to stress will lead to regressive plasticity in the hippocampus and prefrontal cortex, but to progressive plasticity in the amygdala. In this present review, an effort has been made to understand the different alterations in chronic stress models in correlation with clinical conditions, providing evidence on the defective maintenance of glial function and its potential role in the precipitation of neuropsychiatric disorders.

2020 ◽  
Vol 18 (4) ◽  
pp. 457-466
Author(s):  
Marina B. Pavlova ◽  
Alexander I. Vaido ◽  
Diana A.-A. Khlebaeva ◽  
Eugene V. Daev ◽  
Natalia A. Dyuzhikova

We studied changes in the stability of the genome in cells of two brain regions (prefrontal cortex and hippocampus), as well as in the bone marrow of rats with a hereditary high and low thresholds of excitability of the nervous system (strains HT and LT, respectively) after prolonged exposure with emotional-pain stressor. To study the reactivity of the brain cells genome, phosphorylated histone -H2AX (-H2AX phospho Ser139) was used. The level of mitotic disturbances in bone marrow cells was also assessed. Between the animals of the control groups, there were no interstrain differences in the studied parameters. Stress exposure increases the immunoreactivity to -H2AX phospho Ser139 of the prefrontal cortex cells and the level of chromosomal aberrations in bone marrow cells in animals of both strains. In cells of the dentate gyrus of the hippocampus, a specific increase in immunoreactivity to -H2AX phospho Ser139 was revealed in rats of the low-excitable HT strain. The relationship between the reaction of cells of this zone of hippocampus to the stressor exposure with the hereditary level of excitability of the nervous system of animals is discussed.


2021 ◽  
Vol 320 (1) ◽  
pp. C1-C14
Author(s):  
Angelo Tedoldi ◽  
Liam Argent ◽  
Johanna M. Montgomery

One of the major roles of the intracardiac nervous system (ICNS) is to act as the final site of signal integration for efferent information destined for the myocardium to enable local control of heart rate and rhythm. Multiple subtypes of neurons exist in the ICNS where they are organized into clusters termed ganglionated plexi (GP). The majority of cells in the ICNS are actually glial cells; however, despite this, ICNS glial cells have received little attention to date. In the central nervous system, where glial cell function has been widely studied, glia are no longer viewed simply as supportive cells but rather have been shown to play an active role in modulating neuronal excitability and synaptic plasticity. Pioneering studies have demonstrated that in addition to glia within the brain stem, glial cells within multiple autonomic ganglia in the peripheral nervous system, including the ICNS, can also act to modulate cardiovascular function. Clinically, patients with atrial fibrillation (AF) undergoing catheter ablation show high plasma levels of S100B, a protein produced by cardiac glial cells, correlated with decreased AF recurrence. Interestingly, S100B also alters GP neuron excitability and neurite outgrowth in the ICNS. These studies highlight the importance of understanding how glial cells can affect the heart by modulating GP neuron activity or synaptic inputs. Here, we review studies investigating glia both in the central and peripheral nervous systems to discuss the potential role of glia in controlling cardiac function in health and disease, paying particular attention to the glial cells of the ICNS.


2021 ◽  
Vol 11 ◽  
Author(s):  
Franciele F. Scarante ◽  
Melissa A. Ribeiro ◽  
Ana F. Almeida-Santos ◽  
Francisco S. Guimarães ◽  
Alline C. Campos

Cannabidiol (CBD) is a phytocannabinoid with a broad-range of therapeutic potential in several conditions, including neurological (epilepsy, neurodegenerative diseases, traumatic and ischemic brain injuries) and psychiatric disorders (schizophrenia, addiction, major depressive disorder, and anxiety). The pharmacological mechanisms responsible for these effects are still unclear, and more than 60 potential molecular targets have been described. Regarding neuropsychiatric disorders, most studies investigating these mechanisms have focused on neuronal cells. However, glial cells (astrocytes, oligodendrocytes, microglia) also play a crucial role in keeping the homeostasis of the central nervous system. Changes in glial functions have been associated with neuropathological conditions, including those for which CBD is proposed to be useful. Mostly in vitro studies have indicated that CBD modulate the activation of proinflammatory pathways, energy metabolism, calcium homeostasis, and the proliferative rate of glial cells. Likewise, some of the molecular targets proposed for CBD actions are f expressed in glial cells, including pharmacological receptors such as CB1, CB2, PPAR-γ, and 5-HT1A. In the present review, we discuss the currently available evidence suggesting that part of the CBD effects are mediated by interference with glial cell function. We also propose additional studies that need to be performed to unveil the contribution of glial cells to CBD effects in neuropsychiatric disorders.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ali Rafati ◽  
Hajar Yazdani ◽  
Ali Noorafshan

The objective was evaluation of the effects of pioglitazone on medial prefrontal cortex (mPFC) of the rats exposed to aluminum (Al). Al induces structural changes in several brain regions, including mPFC. Pioglitazone is an agonist of peroxisomal proliferator activated receptor gamma. Male rats were randomly assigned to control, Al-treated (10 mg/kg/day), and Al + PIO-treated groups (Al+ 40 mg/kg/day). After 56 days, the right mPFCs were removed. Then, the volume of mPFC and its subdivisions, volume of vessels, and total number of neurons and glia were estimated using stereological methods. The results showed 13–38% decrease in the volume of the mPFC and its subdivisions, mainly in the infralimbic region (P<0.02). Besides, the volume of the vessels reduced by 47% after Al-treatment (P<0.02). The total number of the neurons and glial cells was also reduced (40% and 25%, resp.) in the Al-exposed rats in comparison to the control ones (P<0.02). Treatment of the animals with Al + PIO ameliorated the neuron loss and no improvement was seen in other parameters (P<0.02). It can be concluded that treatment of the rats with PIO could ameliorate the neuron loss in the mPFC of the Al-treated animals.


2021 ◽  
Author(s):  
Simeon O. A. Helgers ◽  
Svilen Angelov ◽  
Marc A. N. Muschler ◽  
Alexander Glahn ◽  
Shadi Al-Afif ◽  
...  

AbstractStructural and functional abnormalities in the cerebellar midline region, including the fastigial nucleus, have been reported in neuropsychiatric disorders, also comprising the cerebellar cognitive affecting syndrome. In rats, early fastigial lesions reduce social interaction during development and lead to cognitive and emotional deficits in adults, accompanied by compromised neuronal network activity. Since epigenetic mechanisms are implicated in the etiology of neuropsychiatric disorders, we investigated whether fastigial nucleus lesions in juvenile rats would impact epigenetic regulation of neural transmission. The fastigial nucleus was lesioned bilaterally in 23-day-old male rats. Sham-lesion and naïve rats served as controls. DNA methylation was investigated for target genes of the GABAergic, dopaminergic, glutamatergic and oxytocinergic systems in brain regions with anatomic connections to the fastigial nucleus, i.e., medial prefrontal cortex, nucleus accumbens, striatum, thalamus, and sensorimotor cortex. Protein expression was examined for the respective target genes in case of altered DNA methylation between lesion and control groups. Lesioning of the fastigial nucleus led to significant differences in the epigenetic regulation of glutamate decarboxylase 1 and the oxytocin receptor in the nucleus accumbens and the prefrontal cortex. No differences were found for the other target genes and brain regions. Our findings indicate that epigenetic dysregulation after lesioning of the fastigial nucleus may influence long-term recovery and the emergence of behavioral changes. Together with previous behavioral and electrophysiological investigations of this rat model, these observations can play a role in the cerebellar cognitive affective syndrome and other neuropsychiatric disorders.


Author(s):  
Wiktor Djaczenko ◽  
Carmen Calenda Cimmino

The simplicity of the developing nervous system of oligochaetes makes of it an excellent model for the study of the relationships between glia and neurons. In the present communication we describe the relationships between glia and neurons in the early periods of post-embryonic development in some species of oligochaetes.Tubifex tubifex (Mull. ) and Octolasium complanatum (Dugès) specimens starting from 0. 3 mm of body length were collected from laboratory cultures divided into three groups each group fixed separately by one of the following methods: (a) 4% glutaraldehyde and 1% acrolein fixation followed by osmium tetroxide, (b) TAPO technique, (c) ruthenium red method.Our observations concern the early period of the postembryonic development of the nervous system in oligochaetes. During this period neurons occupy fixed positions in the body the only observable change being the increase in volume of their perikaryons. Perikaryons of glial cells were located at some distance from neurons. Long cytoplasmic processes of glial cells tended to approach the neurons. The superimposed contours of glial cell processes designed from electron micrographs, taken at the same magnification, typical for five successive growth stages of the nervous system of Octolasium complanatum are shown in Fig. 1. Neuron is designed symbolically to facilitate the understanding of the kinetics of the growth process.


Author(s):  
Prithiv K R Kumar

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.


2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.


Author(s):  
Giedre Milinkeviciute ◽  
Karina S. Cramer

The auditory brainstem carries out sound localization functions that require an extraordinary degree of precision. While many of the specializations needed for these functions reside in auditory neurons, additional adaptations are made possible by the functions of glial cells. Astrocytes, once thought to have mainly a supporting role in nervous system function, are now known to participate in synaptic function. In the auditory brainstem, they contribute to development of specialized synapses and to mature synaptic function. Oligodendrocytes play critical roles in regulating timing in sound localization circuitry. Microglia enter the central nervous system early in development, and also have important functions in the auditory system’s response to injury. This chapter highlights the unique functions of these non-neuronal cells in the auditory system.


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