Advantages and Limitations of Animal Schizophrenia Models

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jun 10

PMID 35682647

Authors

Magdalena Bialon

Agnieszka Wasik

Affiliations

Soon will be listed here.

Abstract

Mental illness modeling is still a major challenge for scientists. Animal models of schizophrenia are essential to gain a better understanding of the disease etiopathology and mechanism of action of currently used antipsychotic drugs and help in the search for new and more effective therapies. We can distinguish among pharmacological, genetic, and neurodevelopmental models offering various neuroanatomical disorders and a different spectrum of symptoms of schizophrenia. Modeling schizophrenia is based on inducing damage or changes in the activity of relevant regions in the rodent brain (mainly the prefrontal cortex and hippocampus). Such artificially induced dysfunctions approximately correspond to the lesions found in patients with schizophrenia. However, notably, animal models of mental illness have numerous limitations and never fully reflect the disease state observed in humans.

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References

Le Pen G, Gourevitch R, Hazane F, Hoareau C, Jay T, Krebs M . Peri-pubertal maturation after developmental disturbance: a model for psychosis onset in the rat. Neuroscience. 2006; 143(2):395-405. DOI: 10.1016/j.neuroscience.2006.08.004. View

Lodge D, Behrens M, Grace A . A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci. 2009; 29(8):2344-54. PMC: 2754752. DOI: 10.1523/JNEUROSCI.5419-08.2009. View

Rowland L . Subanesthetic ketamine: how it alters physiology and behavior in humans. Aviat Space Environ Med. 2005; 76(7 Suppl):C52-8. View

Lu B, Martinowich K . Cell biology of BDNF and its relevance to schizophrenia. Novartis Found Symp. 2008; 289:119-29. PMC: 3096549. DOI: 10.1002/9780470751251.ch10. View

Piskorowski R, Nasrallah K, Diamantopoulou A, Mukai J, Hassan S, Siegelbaum S . Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome. Neuron. 2016; 89(1):163-76. PMC: 4706988. DOI: 10.1016/j.neuron.2015.11.036. View

Ma X, Fei E, Fu C, Ren H, Wang G . Dysbindin-1, a schizophrenia-related protein, facilitates neurite outgrowth by promoting the transcriptional activity of p53. Mol Psychiatry. 2011; 16(11):1105-16. DOI: 10.1038/mp.2011.43. View

Mullin A, Sadanandappa M, Ma W, Dickman D, VijayRaghavan K, Ramaswami M . Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity. J Neurosci. 2015; 35(1):325-38. PMC: 4287151. DOI: 10.1523/JNEUROSCI.3542-14.2015. View

Giovanoli S, Engler H, Engler A, Richetto J, Voget M, Willi R . Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science. 2013; 339(6123):1095-9. DOI: 10.1126/science.1228261. View

Kaminitz A, Barzilay R, Segal H, Taler M, Offen D, Gil-Ad I . Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression. World J Biol Psychiatry. 2013; 15(1):76-82. DOI: 10.3109/15622975.2013.841993. View

10.

Fisken R, Ward R . Discrimination difficulty, cognitive burden, and reversal impairments in a maternal immune activation model of schizophrenia risk. Behav Processes. 2019; 167:103936. DOI: 10.1016/j.beproc.2019.103936. View

11.

Thomson D, McVie A, Morris B, Pratt J . Dissociation of acute and chronic intermittent phencyclidine-induced performance deficits in the 5-choice serial reaction time task: influence of clozapine. Psychopharmacology (Berl). 2010; 213(4):681-95. DOI: 10.1007/s00213-010-2020-7. View

12.

Xiao X, Xu X, Li F, Xie G, Zhang T . Anti-inflammatory treatment with β-asarone improves impairments in social interaction and cognition in MK-801 treated mice. Brain Res Bull. 2019; 150:150-159. DOI: 10.1016/j.brainresbull.2019.05.017. View

13.

Honeycutt J, Keary Iii K, Kania V, Chrobak J . Developmental Age Differentially Mediates the Calcium-Binding Protein Parvalbumin in the Rat: Evidence for a Selective Decrease in Hippocampal Parvalbumin Cell Counts. Dev Neurosci. 2016; 38(2):105-14. DOI: 10.1159/000444447. View

14.

Exposito-Alonso D, Osorio C, Bernard C, Pascual-Garcia S, Del Pino I, Marin O . Subcellular sorting of neuregulins controls the assembly of excitatory-inhibitory cortical circuits. Elife. 2020; 9. PMC: 7755390. DOI: 10.7554/eLife.57000. View

15.

Amitai N, Kuczenski R, Margarita Behrens M, Markou A . Repeated phencyclidine administration alters glutamate release and decreases GABA markers in the prefrontal cortex of rats. Neuropharmacology. 2011; 62(3):1422-31. PMC: 3107933. DOI: 10.1016/j.neuropharm.2011.01.008. View

16.

Rajagopal L, Ryan C, Elzokaky A, Burstein E, Meltzer H . Pimavanserin augments the efficacy of atypical antipsychotic drugs in a mouse model of treatment-refractory negative symptoms of schizophrenia. Behav Brain Res. 2021; 422:113710. DOI: 10.1016/j.bbr.2021.113710. View

17.

Chen G, Lin X, Li G, Jiang D, Lib Z, Jiang R . Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment. Biomed Rep. 2017; 6(3):285-290. PMC: 5403402. DOI: 10.3892/br.2017.850. View

18.

Bringas M, Morales-Medina J, Flores-Vivaldo Y, Negrete-Diaz J, Aguilar-Alonso P, Leon-Chavez B . Clozapine administration reverses behavioral, neuronal, and nitric oxide disturbances in the neonatal ventral hippocampus rat. Neuropharmacology. 2011; 62(4):1848-57. DOI: 10.1016/j.neuropharm.2011.12.008. View

19.

Sawahata M, Asano H, Nagai T, Ito N, Kohno T, Nabeshima T . Microinjection of Reelin into the mPFC prevents MK-801-induced recognition memory impairment in mice. Pharmacol Res. 2021; 173:105832. DOI: 10.1016/j.phrs.2021.105832. View

20.

Dickerson D, Overeem K, Wolff A, Williams J, Abraham W, Bilkey D . Association of aberrant neural synchrony and altered GAD67 expression following exposure to maternal immune activation, a risk factor for schizophrenia. Transl Psychiatry. 2014; 4:e418. PMC: 4119228. DOI: 10.1038/tp.2014.64. View