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.

Experimental Pulmonary Tuberculosis in the Absence of Detectable Brain Infection Induces Neuroinflammation and Behavioural Abnormalities in Male BALB/c Mice

“…Neuroinflammation in the cerebellum results in mild cognitive and motor impairment [ 23 ]. Our results showed in the cerebellum a significant increase in the expression of TNFα and IFNγ from day 1 and for IL-12 from day 14 post-infection ( Figure 4 ).…”

Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases

“…Ketogenic diet- and EKSs-generated ketosis, βHB or the Deanna protocol, containing (among others) MCTs, can also generate alleviating effects on (i) motor neurons and motor performance in preclinical rodent models, such as animal models of amyotrophic lateral sclerosis [ 48 , 332 , 333 , 334 , 335 , 336 ] and (ii) dopaminergic neurons and motor performance in animal models of Parkinson’s disease [ 55 , 258 ] likely through improved mitochondrial function and ATP synthesis ( Table 1 ). Dysregulation of different neurotransmitter systems may have a role in the pathophysiology of neurodegenerative diseases, for example, in animal models and patients with impaired motor function (e.g., dopaminergic dysfunction; GABA and glutamate imbalance) [ 337 , 338 , 339 , 340 ], Parkinson’s disease (e.g., decrease in serotonin level and increase in glutamatergic transmission), Alzheimer’s disease (decreased cholinergic neurotransmission) and both Alzheimer’s disease and Parkinson’s disease (deficits in dopaminergic signaling) [ 337 , 339 , 341 , 342 , 343 ]. Moreover, dysfunctions in neurotransmitter systems (e.g., GABAergic, glutamatergic and cholinergic) can lead to impaired learning and memory [ 340 , 342 , 344 ].…”

“…Indeed, previous studies show that ketosis (βHB) may evoke therapeutic effects in the treatment of Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis and enhance learning and memory through anti-inflammatory effects induced by HCAR2 [ 50 , 55 , 57 , 58 , 275 , 279 ]. It was also demonstrated that enhanced expression of proinflammatory cytokines and oxidative stress have a role in the development of Alzheimer’s disease [ 276 , 356 , 357 ], Parkinson’s disease [ 55 , 276 , 356 , 357 ], amyotrophic lateral sclerosis [ 356 , 357 , 358 ], impaired motor functions [ 337 , 359 ] and impairment of learning and memory [ 309 , 310 , 360 ]. Thus, ketosis may also improve symptoms of neurodegenerative diseases, motor, learning and memory dysfunctions through anti-inflammatory and anti-oxidative effects via HCAR2 [ 50 , 275 , 361 ] ( Figure 2 ).…”

Blood biomarker levels of methylation capacity in autism spectrum disorder: a systematic review and meta‐analysis

“…Neurotransmitters play a crucial part in the development and function of the nervous system, and slight changes in neurochemical levels may have significant impacts on the psychobehaviour of the subject (67). Glutamate, serotonin, gamma‐aminobutyric acid (GABA), and dopamine (just to name a few) interact in regulating physiological and psychiatric manifestations, such as emotion, behaviour, and cognition (68), while abnormalities in these neurotransmitters have been thought to be linked to ASD (69,70). Therefore, we hypothesize that the neurotransmitter system may have a particularly important mediating role in the association of aberrant methylation ability with ASD.…”