Role of Neuroglia in the Habenular Connection Hub of the Dorsal Diencephalic Conduction System

Abstract

Astrocytes and microglia play important roles in organizing the structure and function of neuronal networks in the central nervous system (CNS). The dorsal diencephalic connection system (DDCS) is a phylogenetically ancient regulatory system by which the forebrain influences the activity of cholinergic and ascending monoaminergic pathways in the midbrain. The DDCS is probably important in inducing aspects of mental disorders, such as depression and addiction. The habenula is the small but highly complex connecting center of the DDCS in the epithalamus that consists of a medial (MHb) and lateral (LHb) division. MHb and LHb are built differently and connect different brain structures. Studies in animal models and human biomarker research provide good evidence that astroglia and microglia also affect the symptoms of mental disorders (such as depression). The significance of these neuroglia in habenular neurotransmission has not been extensively studied. This review article provides arguments for doing so more thoroughly.

Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic pain

“…This makes the lateral habenula imperative for the integration of emotional, cognitive, sensory and motor processing to ultimately influence value-based decision-making and motivational processing (50). It has been widely recognised, using fMRI resolutions, that the lateral habenula plays a significant role as an 'anti-reward center' in the mechanism of addiction and major depression (51). Ketamine has been shown to inhibit burst firing from the lateral habenula via NMDA receptor antagonism (52).…”

Putative role of immune reactions in the mechanism of tardive dyskinesia

“…The neuroinflammatory changes leading to the development of TD need not take place in the striatum. Immune activation outside the central nervous system has important im-plications for neuroinflammatory processes in cerebro ( Miller and Raison, 2016 ; Erickson and Banks, 2018 ; Gonçalves and De Felice, 2021 ; Loonen, 2023 ). It is possible that the elevated IL-1β is not produced in the striatum, because the corresponding mRNA levels are not elevated there ( Sonego et al, 2018 ).…”

“…Dyskinesia also occurs spontaneously in people with schizophrenia ( Fenton, 2000 ; Lee et al, 2008 ; Pappa and Dazzan, 2009 ; Koning et al, 2010 ; Walther and Mittal, 2017 ), their siblings ( McCreadie et al, 2003 ; Koning et al, 2010 ) and – although the true incidence is debated ( Ticehurst, 1990 ) – in older individuals ( Blanchet et al, 2004 ; Merrill et al, 2013 ). By definition, the included patients are treated with dopamine 2 antagonists (antipsychotics) which by themselves might have immune modulating effects via these receptors ( Xia et al, 2019 ; Loonen, 2023 ). Moreover, antipsychotics have other side effects involving inflammatory processes, such as hepatotoxicity ( Todorović Vukotić et al, 2021 ) and metabolic syndrome ( Leonard et al, 2012 ; Fang et al, 2020 ).…”

“…They cause local inflammatory responses along this pathway but also have a great influence on the structure and function of neuronal networks ( Wolf et al, 2017 ; Sancho et al, 2021 ). In a recent article, I suggested that neuroinflammation probably also affects neurocommunicative processes within the DDCS ( Loonen, 2023 ). Another border between the periphery and the brain that may be bridged by immunocommunication is the blood cerebrospinal fluid barrier (BCSFB) and especially that in the choroid plexus where most of the cerebrospinal fluid (CSF) is produced ( Demeestere et al, 2015 ; Tumani et al, 2017 ; Cui et al, 2021 ; Gião et al, 2022 ; Santos-Lima et al, 2022 ).…”

“…In addition to activation by, for example, pathogen entry into the CNS ( Boche et al, 2013 ; Bernaus et al, 2020 ; Mattei and Notter, 2020 ; Deng et al, 2020 ), the immune response can also be initiated from the periphery ( Miller and Raison, 2016 ; Kim and Won, 2017 ; Gonçalves and De Felice, 2021 ; Bottaccioli et al, 2022 ). This means, on the one hand, that forms of psychological stress through activation of an immune response, for example, via the autonomic nervous system, could trigger a neuroinflammatory process in the CNS and, on the other hand, that tissue damage elsewhere in the body through the initiation of an immune response could also be responsible for a neuroinflammatory process in the CNS ( Loonen, 2023 ).…”