Review on Cross Talk between Neurotransmitters and Neuroinflammation in Striatum and Cerebellum in the Mediation of Motor Behaviour

Abstract

Neurological diseases particularly Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and epilepsy are on the rise all around the world causing morbidity and mortality globally with a common symptom of gradual loss or impairment of motor behaviour. Striatum, which is a component of the basal ganglia, is involved in facilitating voluntary movement while the cerebellum is involved in the maintenance of balance and coordination of voluntary movements. Dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate, to name a few, interact in regulating the excitation and inhibition of motor neurons. In another hand, interestingly, the motor loss associated with neurological diseases is possibly resulted from neuroinflammation induced by the neuroimmune system. Toll-like receptors (TLRs) are present in the central nervous system (CNS), specifically and primarily expressed in microglia and are also found on neurons and astrocytes, functioning mainly in the regulation of proinflammatory cytokine production. TLRs are always found to be associated or involved in the induction of neuroinflammation in neurodegenerative diseases. Activation of toll-like receptor 4 (TLR4) through TLR4 agonist, lipopolysaccharide (LPS), stimulation initiate a signaling cascade whereby the TLR4-LPS interaction has been found to result in physiological and behavioural changes including retardation of motor activity in the mouse model. TLR4 inhibitor TAK-242 was reflected in the reduction of the spinal cord pathology along with the motor improvement in ALS mouse. There is cross talk with neuroinflammation and neurochemicals. For example, TLR4 activation by LPS is noted to release proinflammatory cytokines, IL-1β, from microglia that subsequently suppresses GABA receptor activities at the postsynaptic site and reduces GABA synthesis at the presynaptic site. Glial glutamate transporter activities are also found to be suppressed, showing the association between TLR4 activation and the related neurotransmitters and corresponding receptors and transporters in the event of neuroinflammation. This review is helpful to understand the connection between neurotransmitter and neuroinflammation in striatum- and cerebellum-mediated motor behaviour.