TY  - JOUR
A1  - Gorlova, Anna
A1  - Svirin, Evgeniy
A1  - Pavlov, Dmitrii
A1  - Cespuglio, Raymond
A1  - Proshin, Andrey
A1  - Schroeter, Careen A.
A1  - Lesch, Klaus-Peter
A1  - Strekalova, Tatyana
T1  - Understanding the role of oxidative stress, neuroinflammation and abnormal myelination in excessive aggression associated with depression: recent input from mechanistic studies
JF  - International Journal of Molecular Sciences
N2  - Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients. Due to the complex nature and the clinical heterogeneity of MDD and the lack of precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, the aetiology and pathophysiology of MDD has been the subject of extensive research and there is a vast body of the latest literature that points to new mechanisms for this disorder. Here, we overview the key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling and abnormal myelination. We discuss the hypotheses that have been proposed to unify these processes, as many of these pathways are integrated for the neurobiology of MDD. We also describe the current translational approaches in modelling depression, including the recent advances in stress models of MDD, and emerging novel therapies, including novel approaches to management of excessive aggression, such as anti-diabetic drugs, antioxidant treatment and herbal compositions.
KW  - major depressive disorder (MDD)
KW  - aggression
KW  - neuroinflammation
KW  - oxidative stress
KW  - insulin receptor
KW  - myelination
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304917
SN  - 1422-0067
VL  - 24
IS  - 2
ER  - 
TY  - JOUR
A1  - Sun, Ping
A1  - Ortega, Gabriela
A1  - Tan, Yan
A1  - Hua, Qian
A1  - Riederer, Peter F.
A1  - Deckert, Jürgen
A1  - Schmitt-Böhrer, Angelika G.
T1  - Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system
JF  - Frontiers in Aging Neuroscience
N2  - Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders.
KW  - Alzheimer’s disease
KW  - streptozotocin
KW  - proliferation
KW  - neural stem cells
KW  - insulin-like growth factor 1 receptor
KW  - insulin receptor
KW  - glucose transporter
KW  - differentiation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176741
VL  - 10
IS  - 145
ER  -