Reduced hippocampus volume in the mouse model of Posttraumatic Stress Disorder

Golub, Yulia; Kaltwasser, Sebastian F.; Mauch, C.; Herrmann, Leonie; Schmidt, Ulrike; Holsboer, Florian; Czisch, Michael; Wotjak, Carsten T.

doi:10.1016/j.jpsychires.2010.10.014

Cited by 101 publications

(76 citation statements)

References 56 publications

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“…Our results also demonstrate that reduced PTPN5 expression heightened neuronal vulnerability to glutamate and Bay K8644 induced toxicity. This observation is consistent with the view that smaller hippocampal volumes in depression or PTSD patients might result from excessive glutamate-induced excitotoxicity (Golub et al, 2011).…”

supporting

confidence: 92%

A Critical Role for Protein Tyrosine Phosphatase Nonreceptor Type 5 in Determining Individual Susceptibility to Develop Stress-Related Cognitive and Morphological Changes

Yang

Huang

2012

J. Neurosci.

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While stressful life events confer increased risk for the development of psychopathology, most individuals experiencing adversity maintain normal psychological functioning, suggesting that individual differences may influence the susceptibility to develop stress-related psychiatric disorders. However, little is known about what determines this difference between individuals at the molecular level. In the present study, we identify that protein tyrosine phosphatase nonreceptor type 5 (PTPN5) (also known as STEP) is a critical determinant of differences in individual susceptibility to develop stress-related cognitive and morphological changes in rats. Our data demonstrate that ablation of PTPN5 expression delays physiological recovery from stress and augments the development of stress-related cognitive and morphological changes, whereas overexpression of a constitutively active variant of PTPN5 enhances the individual's resilience to stress. Our data also reveal that reduced PTPN5 expression prolongs the duration of extracellular signal-regulated kinase activation, leading to an elevation of Ca V 1.2 channel expression and a recovery delay of K V 4.2 channels from inactivation, which in turn heightens neuronal vulnerability to glutamate toxicity. Moreover, intraperitoneal injections of L-type Ca 2ϩ channel blocker nifedipine after stress resulted in a significantly lower rate for developing stress-related cognitive and morphological changes seen in PTPN5 knockdown rats. Together, these results identify a novel role for PTPN5 in mediating the development of stress-related cognitive and morphological changes and suggest that people with PTPN5 deficiency may have a greater susceptibility to capture the deleterious effects of stress.

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supporting

confidence: 92%

A Critical Role for Protein Tyrosine Phosphatase Nonreceptor Type 5 in Determining Individual Susceptibility to Develop Stress-Related Cognitive and Morphological Changes

Yang

Huang

2012

J. Neurosci.

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“…Developmental lesions of the ventral hippocampus produce an animal model of schizophrenia (Lipska et al, 2002;Swerdlow et al, 2001). Hippocampal volume reductions are reported in patients suffering from various mental disorders such as depression, anxiety, and schizophrenia (Campbell et al, 2004;Nelson et al, 1998;Sheline et al, 2003;Vythilingam et al, 2002), as well as in animal models of these diseases (Gilabert-Juan et al, 2013;Golub et al, 2011;Kaae et al, 2012;Kalisch et al, 2006). Understanding how the hippocampus is changed in the context of mental disorders will provide clues to their etiology and new avenues for prevention and treatment of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Adult Neurogenesis and Mental Illness

Schoenfeld

Cameron

2014

Neuropsychopharmacol

162

108

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Several lines of evidence suggest that adult neurogenesis, the production of new neurons in adulthood, may play a role in psychiatric disorders, including depression, anxiety, and schizophrenia. Medications and other treatments for mental disorders often promote the proliferation of new neurons; the time course for maturation and integration of new neurons in circuitry parallels the delayed efficacy of psychiatric therapies; adverse and beneficial experiences similarly affect development of mental illness and neurogenesis; and ablation of new neurons in adulthood alters the behavioral impact of drugs in animal models. At present, the links between adult neurogenesis and depression seem stronger than those suggesting a relationship between new neurons and anxiety or schizophrenia. Yet, even in the case of depression there is currently no direct evidence for a causative role. This article reviews the data relating adult neurogenesis to mental illness and discusses where research needs to head in the future.

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“…Interestingly, up-and down-regulation of GAP43 expression points to a respective pruning and strengthening of neuronal interconnectivity in response to traumatizing or complex stimulating experiences and is very likely part of the biological mechanisms responsible for the observed volume A C C E P T E D M A N U S C R I P T differences (Golub, Kaltwasser et al 2011). Likewise, and found independently that treadmill pre-training reduced cerebral edema in case of ischemic stroke.…”

Section: Accepted Manuscriptmentioning

confidence: 86%

Neuroplasticity and MRI: A perfect match

2016

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Numerous studies have illustrated the benefits of physical workout and cognitive exercise on brain function and structure and, more importantly, on decelerating cognitive decline in old age and promoting functional rehabilitation following injury. Despite these behavioral observations, the exact mechanisms underlying these neuroplastic phenomena remain obscure. This gap illustrates the need for carefully designed in-depth studies using valid models and translational tools which allow to uncover the observed events up to the molecular level. We promote the use of in vivo magnetic resonance imaging (MRI) because it is a powerful translational imaging technique able to extract functional, structural, and biochemical information from the entire brain. Advanced processing techniques allow performing voxel-based analyses which are capable of detecting novel loci implicated in specific neuroplastic events beyond traditional regions-of-interest analyses. In addition, its non-invasive character sets it as currently the best global imaging tool for performing dynamic longitudinal studies on the same living subject, allowing thus exploring the effects of experience, training, treatment etc. in parallel to additional measures such as age, cognitive performance scores, hormone levels, and many others. The aim of this review is (i) to introduce how different animal models contributed to extend the knowledge on neuroplasticity in both health and disease, over different life stages and upon various experiences, and (ii) to illustrate how specific MRI techniques can be applied successfully to inform on the fundamental mechanisms underlying experience-dependent or activity-induced neuroplasticity including cognitive processes.

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Reduced hippocampus volume in the mouse model of Posttraumatic Stress Disorder

Cited by 101 publications

References 56 publications

A Critical Role for Protein Tyrosine Phosphatase Nonreceptor Type 5 in Determining Individual Susceptibility to Develop Stress-Related Cognitive and Morphological Changes

A Critical Role for Protein Tyrosine Phosphatase Nonreceptor Type 5 in Determining Individual Susceptibility to Develop Stress-Related Cognitive and Morphological Changes

Adult Neurogenesis and Mental Illness

Neuroplasticity and MRI: A perfect match

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