Understanding translational research in schizophrenia: A novel insight into animal models

Abstract

Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.

Microglial contribution to the pathology of neurodevelopmental disorders in humans

“…For example, overexpression of C4A in mice increases synaptic uptake by microglia, and leads to altered social behaviour and increased anxiety compared to wildtype and knockout animals [ 214 ], linking findings from genetic studies with mechanistic insights [ 171 ]. As several recent reviews have discussed the latest developments in using animal models in SZ research [ 7 , 106 , 200 ], for the purpose of this review, we will focus primarily on the evidence linking microglia and SZ in human studies.…”

Retinal electrophysiology in central nervous system disorders. A review of human and mouse studies

“…Whilst no main group differences were observed under DA or LA conditions, when the ERGs were recorded under mesopic conditions the reduced a- and b-wave amplitudes and delay in peak times were consistent with human studies in schizophrenia suggesting that mesopic testing conditions may improve the b-wave amplitude as a stronger biomarker for schizophrenia ( Torres Jimenez et al, 2020 ) as suggested in recent human studies ( Hébert et al, 2015 ; Demmin et al, 2018 ). For a review om animal models in schizophrenia see Malik et al (2023) .…”

A Thalamocortical Perspective on Sleep Spindle Alterations in Neurodevelopmental Disorders

“…Recently, rodent models have fueled prominent hypotheses on the pathogenesis of schizophrenia including deficits in dopamine, glutamate/N-methyl-D-aspartate (NMDA) regulation, alterations in neuroimmune/neuroinflammatory responses, deficits in GABA tone, and more recently dysregulation of the oxidative stress system (reviewed in [ 140 – 142 ]). In rodent models, the deficits in oscillatory activity including spindles could represent strong biomarkers linking circuit specificity and system alterations fueling discovery.…”