Expression of mRNA of neurotrophic factors and their receptors are significantly altered after subchronic ketamine treatment.
The neurotrophic factors play an important role in the maintenance of neurone viability and neuronal communication which are considered to be altered in schizophrenia. Subchronic application of ketamine (Ket) was found to be a useful model in schizophrenia research. To further validate this model the mRNA levels of neurotrophic factors NGF, NT-3, and BDNF and their receptors TrkA, TrkB, and TrkC, respectively, were measured in different brain areas in Ket-pretreated rats subchronically dosed with the atypical antipsychotic drug risperidone (Ris). With the exception of NGF in the frontal cortex, Ket pretreatment did change NGF, NT-3, and BDNF mRNA levels in the frontal cortex, the hippocampus, the striatum, the thalamus/hypothalamus region, and in the cerebellum. These changes correspond with changes at their tyrosine kinase receptors. Ris treatment normalised altered NT-3 levels in the hippocampus and balanced BDNF levels in the same structure. It was concluded that the Ket model might reflect distinct alterations in neurotrophic factor activity as found in schizophrenic patients and, moreover, that Ris treatment rebalances disturbed neurotrophic factor activity.
Becker
Axel
A
Otto-von-Guericke University, Faculty of Medicine, Institute of Anatomy, Leipziger Str. 44, 39120 Magdeburg, Germany.
Grecksch
Gisela
G
Schwegler
Herbert
H
Roskoden
Thomas
T
D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics; D020813:Receptor, trkB / Q000096:biosynthesis / Q000235:genetics; D020812:Receptor, trkC / Q000096:biosynthesis / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012559:Schizophrenia / Q000139:chemically induced
D000778:Anesthetics, Dissociative; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D007649:Ketamine; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC