White Matter Injuries Induced by MK‐801 in a Mouse Model of Schizophrenia Based on NMDA Antagonism

Abstract

The etiology of schizophrenia (SZ) is complex and largely unknown. Neuroimaging and postmortem studies have suggested white matter disturbances in SZ. In the present study, we tested the white matter deficits hypothesis of SZ using a mouse model of SZ induced by NMDA receptor antagonist MK-801. We found that mice with repeated chronic MK-801 administration showed increased locomotor activity in the open field test, less exploration of a novel environment in the hole-board test, and increased anxiety in the elevated plus maze but no impairments were observed in coordination or motor function on accelerating rota-rod. The total white matter volume and corpus callosum volume in mice treated with MK-801 were significantly decreased compared to control mice treated with saline. Myelin basic protein and 2 0 , 3 0 -cyclic nucleotide 3 0 -phosphodiesterase were also significantly decreased in the mouse model of SZ. Furthermore, we observed degenerative changes of myelin sheaths in the mouse model of SZ. These results provide further evidence of white matter deficits in SZ and indicate that the animal model of SZ induced by MK-801 is a useful model to investigate mechanisms underlying white

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

“…In experimental studies, chronic treatment with the NMDA receptor antagonist MK-801 in mice have shown demyelination of the corpus callosum with schizophrenia-like behaviors, including hyperlocomotor activity and anxiety. 75,76 This pharmacological model of schizophrenia has also been shown to increase compulsive drinking in rats on SIP. 21 Moreover, animal models of schizophrenia, based on maternal immune activation, have also shown a reduction in myelinated fibers in the BLA amygdala, as well as long-lasting prepulse inhibition (PPI) deficits, locomotor hyperactivity and working memory deficits.…”

The neurobiology of transition to psychosis

“…Third, dys myelination is consistently noted in neurodevelopmental models that reproduce behavioural features reminiscent of negative symptoms of schizophrenia. This includes perinatal and subchronic administration of phencyclidine, [70][71][72][73][74] ), early social isolation, 80 and excitotoxic developmental lesion models (medial prefrontal 81 ). Cuprizone, a copper chelating agent that actively disrupts myelination, results in diminished social interaction in mice, [81][82][83][84][85][86] but only when dys myelination occurs before adult life.…”

Farelerde NMDA Reseptör Antagonisti Mk-801 İle Böbrek ve Karaciğerde Oluşan Histopatolojik Değişikliklere Karşı Resveratrolün Koruyucu Etkisi

“…N-methyl-D-aspartate (NMDA) receptors are an important factor in the synapse mechanism of the glutamatergic system [1,2] . Hypofunction of these receptors may cause cognitive and motor problems [3][4][5][6][7][8] . The chemical agent MK-801 is a blocking and neurotoxic antagonist of this receptor [6][7][8] .…”

“…Hypofunction of these receptors may cause cognitive and motor problems [3][4][5][6][7][8] . The chemical agent MK-801 is a blocking and neurotoxic antagonist of this receptor [6][7][8] . Blocking of this receptor by the 1 mg/kg  İletişim (Correspondence)  +90 272 2281312  akosmans@yahoo.com sub-chronic dose of MK-801 causes neurodegeneration, demyelination, and schizophrenia-like symptoms in mice [7,8] .…”

“…The chemical agent MK-801 is a blocking and neurotoxic antagonist of this receptor [6][7][8] . Blocking of this receptor by the 1 mg/kg  İletişim (Correspondence)  +90 272 2281312  akosmans@yahoo.com sub-chronic dose of MK-801 causes neurodegeneration, demyelination, and schizophrenia-like symptoms in mice [7,8] . In addition, transporters and receptors of the glutamatergic system are found in many internal organs such as the testis, intestine, heart, lung, liver and kidney [9] .…”