Tryptophan hydroxylase-2 immunoreactivity changes in the dorsal raphe nucleus after chronic methamphetamine or corticosterone in BDNF-deficient mice models: Implications for schizophrenia
AffiliationFlorey Department of Neuroscience and Mental Health
Document TypeMasters Research thesis
Access StatusThis item is embargoed and will be available on 2021-03-21.
© 2018 Mauricio Sepulveda Fernandez
Schizophrenia is a major mental illness caused by genetic and environmental factors. In addition to dopaminergic dysfunction, evidence has associated 5-hydroxytryptamine (serotonin) with schizophrenia. The serotonergic system interacts with the neurotrophin, Brain-Derived Neurotrophic Factor (BDNF), resulting in behavioural and anatomical changes relevant to schizophrenia. The aim of this study was to determine changes in the number of serotonergic cells within the dorsal raphe nucleus (DR) in BDNF-deficient mice (BDNF heterozygous and BDNF Val66Met polymorphism) after chronic treatment with methamphetamine (METH) or the stress hormone, corticosterone (CORT). Chronic METH abuse may lead to psychosis and dopaminergic dysfunction. Chronic stress is a risk factor for schizophrenia in vulnerable individuals. Cell quantification and density analysis were based on the immunoreactivity of the serotonin-synthesizing enzyme, tryptophan-hydroxylase 2 (TPH2), within subnuclei of the DR: DR caudal (DRC), DR dorsal (DRD), DR interfascicular (DRI), DR ventral (DRV) and DR ventrolateral (DRVL) subnuclei. Results can be summarized as follows: 1) METH was able to decrease the number of TPH2-immunoreactive (TPH2-ir) cells in both BDNF-deficient models within the medial and caudal DRVL subnuclei; 2) BDNF-deficiency resulted in reductions in the number of TPH2-ir cells in a subnucleus- and treatment-specific way; namely BDNF heterozygosity induced a reduction in METH-treated mice within the DRVL subnucleus, whilst the BDNF Val66Met polymorphism resulted a reduction of TPH2-ir neurons in vehicle-treated mice within the caudal part of the DRVL subnuclei. The latter finding was also observed through density analysis; 3) CORT treatment increased TPH-ir neurons in the rostral DRV and the caudal DRVL of Val/Met mice; and 4) Noticeably, there were no changes within the DRD, DRC or DRI subnuclei regardless of the BDNF-deficiency or treatment. These results suggest that the number of TPH2-ir cells is dependent on BDNF levels as well as on a history of stress or methamphetamine abuse. These changes induced by BDNF-deficiency or the treatments are subnucleus-specific, affecting more the rostral, caudal and lateral edges rather than core and dorsal areas of the DR. The results suggest that these subnuclei-specific effects may have implications for brain regions dif-ferentially innervated by these subnuclei, including the amygdala, hippocampus and periaqueductal gray, which are involved in schizophrenia and mood disorders.
Keywordsbrain-derived neurotrophic factor; dorsal raphe; tryptophan hydroxylase; corticosterone; methamphetamine
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References