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The temporal dynamics in the stressed brain
S113
Symposia
S.01. Life on the brink: social stress and psychopathology S.01.02 Stress and antidepressants: time-dependent changes in synaptic function and brain architecture M. Popoli1 ° 1 University of Milan, Laboratory of Neuropsychopharmacology and Functional Neurogenomics Department of Pharmacological and Biomolecular Sciences, Milan, Italy Stressful life events represent major risk factors for stress-related neuropsychiatric disorders [1]. Neuroimaging studies have shown volumetric reduction and remodeling of neuroarchitecture in brain areas of psychiatric patients, while chronic stress models in rodents have consistently shown reduction of synaptic spines and atrophy/remodeling of dendrites, thus suggesting that stress-induced maladaptive changes have a primary role in psychopathology. Whereas the effects of chronic stress have been investigated at length in animal models, the short- and long-term consequences of acute stressors have been little or not investigated, although it has been shown that in some cases (e.g., PTSD) the first few hours after trauma are crucial for pathophysiological outcome and therapeutic intervention [2]. We have shown previously that acute inescapable stress rapidly enhances glutamate release/transmission in prefrontal/frontal cortex (PFC/FC), by synaptic corticosterone (CORT) receptorsdependent non-genomic increase of readily releasable pool (RRP) of vesicles in perforated synapses [3]. Recently, by using EMstereology, we found that after 40 min of inescapable stress, the enhancement of glutamate release/transmission in PFC was accompanied by a dramatic increase (42.6%) of total number of excitatory synapses (restricted to non-perforated and axo-spinous synapses), an effect prevented by antidepressant treatment [4]. Spine density was elevated up to 24 h but returned to normal level later; instead dendritic arborization was already reduced 24 h after stress [5]. These results showed for the first time that a single exposure to stress can exert bi-phasic, complex and remarkable effects on PFC architecture, both rapid and sustained in time. References [1] Popoli, M., Yan, Z., McEwen, B.S., Sanacora, G., 2012. The stressed synapse: the impact of behavioral stress and glucocorticoids on glutamate transmission. Nature Rev Neurosci 13:22−37. [2] Zohar, J., Yahalom, H., Kozlovsky, N., Cwikel-Hamzany, S., Matar, M.A., Kaplan, Z., Yehuda, R., Cohen, H., 2011. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies. Eur Neuropsychopharmacol 21:796–809. [3] Treccani, G., Musazzi, L., Perego, C., Milanese, M., Nava, N., Bonifacino, T., Lamanna, J., Malgaroli, A., Drago, F., Racagni, G., Nyengaard, J.R., Wegener, G., Bonanno, G., Popoli, M., 2014 Stress and corticosterone increase the readily releasable pool of glutamate vesicles in synaptic terminals of prefrontal and frontal cortex. Mol Psychiatry 19:433–443. [4] Nava, N., Treccani, G., Liebenberg, N., Chen, F., Popoli, M., Wegener, G., Nyengaard, J.R., 2014. Chronic desipramine prevents acute
stress-induced reorganization of medial prefrontal cortex architecture by blocking glutamate vesicle accumulation and excitatory synapse increase. Int J Neuropsychopharmacol 18:3. [5] M., Wegener, G., Nyengaard, J.R., 2015. Temporal Dynamics of Acute Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex and the Protective Effect of Desipramine. Cereb Cortex (Epub ahead of print).
S.01.04 The temporal dynamics in the stressed brain N. Sousa1 ° 1 University of Minho School of Health Sciences, Braga, Portugal Accumulating evidence reveals that stressful stimuli in healthy subjects trigger activation of a consistent and reproducible set of brain regions; yet, the notion that there is a single and constant stress neuromatrix is not sustainable. Moreover, after chronic stress exposure there is activation of many brain regions outside that network. This suggests that there is a distinction between the acute- and the chronic-stress neuromatrix. During this talk, a new working model to understand the shift between these networks will be presented; in this model there are independent, albeit interacting, steps, which are modulated by factors that may explain the dynamics of the chronic stress brain construct: (i) susceptibility; (ii) response and initial injury; (iii) transition to chronicity; (iv) maintenance of a “stressed-brain”. As a result, in the chronic stress stage, perception and salience of a stressor is a modified emotional and hedonic construct, where threat/ value assessment and memory traces of stressful experiences are incorporated, eventually in an “altered mode”. Indeed, according to this model the transition from acute to chronic stress entails also a transition in the salience of a stressor from a simple sign of external threat/challenge into a pathological construct. Thus, the understanding of the factors that modulate these networks and their interplay will allow for a more comprehensive and holistic perspective of how the brain shifts “back and forth” from a healthy to a stressed pattern and, ultimately, how the latter can be a trigger for several neurological and psychiatric conditions.
S.02. Alzheimer-type dementia in people with Down syndrome S.02.01 Alzheimer’s disease in older individuals with Down syndrome A. Strydom1 ° 1 University College London, Division of Psychiatry, London, United Kingdom Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with Alzheimer’s disease (AD) due to amyloid overproduction and subsequent development of amyloid plaques in the central nervous system. AD is so common amongst people with DS that it could be considered a defining feature of the condition. This is believed to be due to the Amyloid Precursor
Symposia
S.01. Life on the brink: social stress and psychopathology S.01.02 Stress and antidepressants: time-dependent changes in synaptic function and brain architecture M. Popoli1 ° 1 University of Milan, Laboratory of Neuropsychopharmacology and Functional Neurogenomics Department of Pharmacological and Biomolecular Sciences, Milan, Italy Stressful life events represent major risk factors for stress-related neuropsychiatric disorders [1]. Neuroimaging studies have shown volumetric reduction and remodeling of neuroarchitecture in brain areas of psychiatric patients, while chronic stress models in rodents have consistently shown reduction of synaptic spines and atrophy/remodeling of dendrites, thus suggesting that stress-induced maladaptive changes have a primary role in psychopathology. Whereas the effects of chronic stress have been investigated at length in animal models, the short- and long-term consequences of acute stressors have been little or not investigated, although it has been shown that in some cases (e.g., PTSD) the first few hours after trauma are crucial for pathophysiological outcome and therapeutic intervention [2]. We have shown previously that acute inescapable stress rapidly enhances glutamate release/transmission in prefrontal/frontal cortex (PFC/FC), by synaptic corticosterone (CORT) receptorsdependent non-genomic increase of readily releasable pool (RRP) of vesicles in perforated synapses [3]. Recently, by using EMstereology, we found that after 40 min of inescapable stress, the enhancement of glutamate release/transmission in PFC was accompanied by a dramatic increase (42.6%) of total number of excitatory synapses (restricted to non-perforated and axo-spinous synapses), an effect prevented by antidepressant treatment [4]. Spine density was elevated up to 24 h but returned to normal level later; instead dendritic arborization was already reduced 24 h after stress [5]. These results showed for the first time that a single exposure to stress can exert bi-phasic, complex and remarkable effects on PFC architecture, both rapid and sustained in time. References [1] Popoli, M., Yan, Z., McEwen, B.S., Sanacora, G., 2012. The stressed synapse: the impact of behavioral stress and glucocorticoids on glutamate transmission. Nature Rev Neurosci 13:22−37. [2] Zohar, J., Yahalom, H., Kozlovsky, N., Cwikel-Hamzany, S., Matar, M.A., Kaplan, Z., Yehuda, R., Cohen, H., 2011. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies. Eur Neuropsychopharmacol 21:796–809. [3] Treccani, G., Musazzi, L., Perego, C., Milanese, M., Nava, N., Bonifacino, T., Lamanna, J., Malgaroli, A., Drago, F., Racagni, G., Nyengaard, J.R., Wegener, G., Bonanno, G., Popoli, M., 2014 Stress and corticosterone increase the readily releasable pool of glutamate vesicles in synaptic terminals of prefrontal and frontal cortex. Mol Psychiatry 19:433–443. [4] Nava, N., Treccani, G., Liebenberg, N., Chen, F., Popoli, M., Wegener, G., Nyengaard, J.R., 2014. Chronic desipramine prevents acute
stress-induced reorganization of medial prefrontal cortex architecture by blocking glutamate vesicle accumulation and excitatory synapse increase. Int J Neuropsychopharmacol 18:3. [5] M., Wegener, G., Nyengaard, J.R., 2015. Temporal Dynamics of Acute Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex and the Protective Effect of Desipramine. Cereb Cortex (Epub ahead of print).
S.01.04 The temporal dynamics in the stressed brain N. Sousa1 ° 1 University of Minho School of Health Sciences, Braga, Portugal Accumulating evidence reveals that stressful stimuli in healthy subjects trigger activation of a consistent and reproducible set of brain regions; yet, the notion that there is a single and constant stress neuromatrix is not sustainable. Moreover, after chronic stress exposure there is activation of many brain regions outside that network. This suggests that there is a distinction between the acute- and the chronic-stress neuromatrix. During this talk, a new working model to understand the shift between these networks will be presented; in this model there are independent, albeit interacting, steps, which are modulated by factors that may explain the dynamics of the chronic stress brain construct: (i) susceptibility; (ii) response and initial injury; (iii) transition to chronicity; (iv) maintenance of a “stressed-brain”. As a result, in the chronic stress stage, perception and salience of a stressor is a modified emotional and hedonic construct, where threat/ value assessment and memory traces of stressful experiences are incorporated, eventually in an “altered mode”. Indeed, according to this model the transition from acute to chronic stress entails also a transition in the salience of a stressor from a simple sign of external threat/challenge into a pathological construct. Thus, the understanding of the factors that modulate these networks and their interplay will allow for a more comprehensive and holistic perspective of how the brain shifts “back and forth” from a healthy to a stressed pattern and, ultimately, how the latter can be a trigger for several neurological and psychiatric conditions.
S.02. Alzheimer-type dementia in people with Down syndrome S.02.01 Alzheimer’s disease in older individuals with Down syndrome A. Strydom1 ° 1 University College London, Division of Psychiatry, London, United Kingdom Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with Alzheimer’s disease (AD) due to amyloid overproduction and subsequent development of amyloid plaques in the central nervous system. AD is so common amongst people with DS that it could be considered a defining feature of the condition. This is believed to be due to the Amyloid Precursor