scholarly journals Parvabumin interneuron-mediated hippocampal network activity disruption in a two-hit model with relevance to postintensive care syndrome: prevention by fluoxetine

2020 ◽  
Author(s):  
Mu-huo Ji ◽  
JianHua Tong ◽  
Zhi-qiang Zhou ◽  
Jian-Jun Yang
Keyword(s):  
Animal Model ◽  
Underlying Mechanism ◽  
Network Activity ◽  
Gabaergic Interneuron ◽  
Neural Activities ◽  
Fluoxetine Treatment ◽  
Relevant Animal Model ◽  
Gamma Power ◽  
Chronic Fluoxetine ◽  
Hippocampal Network

Abstract Background Postintensive care syndrome (PICS) is defined as a new or worsening impairment in cognition, mental health, and physical function after critical illness, which is associated with reduced quality of life and increased mortality. We recently have developed a clinically relevant animal model of PICS, which can mimic most features of human PICS. However, the underlying mechanism remains largely to be elucidated. Accumulating evidence has suggested that hippocampal GABAergic interneuron dysfunction is implicated in various mood disorders induced by stress. Methods We explored the role of hippocampal GABAergic interneurons and relevant neural activities in an animal model of PICS based on two-hit hypothesis. In addition, we tested whether fluoxetine treatment early following combined stress can prevent subsequent anatomical and behavioral pathologies. Results Here our study further supported our previous findings that this PICS model displayed reproducible anxiety- and depression like behavior and cognitive impairments, which resembles clinical features of human PICS. This behavioral state is accompanied by hippocampal neuroinflammation, reduced parvalbumin (PV) expression, and decreased theta and gamma power. Importantly, chronic fluoxetine treatment reversed most of these abnormities. Conclusions Our study provides additional evidence that PV interneuron-mediated hippocampal network activity disruption might play a key role in the pathological of PICS, while fluoxetine offers protection via modulation of the hippocampal PV interneuron and relevant network activities.

scholarly journals Neuroinflammation-Induced Parvalbumin Interneuron and Oscillation Deficits Might Contribute to Neurobehavioral Abnormities in a Two-Hit Model of Depression

2021 ◽  
Author(s):  
Fei Wang ◽  
Jianhua Tong ◽  
Yuzhu Gao ◽  
Shixu Wang ◽  
Muhuo Ji
Keyword(s):  
Gamma Oscillations ◽  
Underlying Mechanism ◽  
Male Mice ◽  
Chronic Unpredictable Stress ◽  
Reduced Body ◽  
Fluoxetine Treatment ◽  
Parvalbumin Interneuron ◽  
Chronic Fluoxetine ◽  
Profound Disability ◽  
And Behavior

Abstract Background: Depression is a common neuropsychiatric disorder that causes profound disability worldwide, yet the underlying mechanism remains unclear. Thus, the present study aimed to evaluate the effects of a two-hit model of depression on glial activation, parvalbumin (PV) interneuron, oscillation activity, and behavior alternations, and whether chronic fluoxetine treatment can reverse these abnormalities. Methods: Male mice were submitted to lipopolysaccharide (LPS) injection, followed by a modified chronic unpredictable stress (CUS) protocol. Results: In our study, we showed that mice exposed to LPS and CUS exhibited reduced body weight, anhedonic-like behavior as well as cognitive and anxiety symptoms. These behavioral alternations were related to enhanced neuroinflammation, as reflected by significantly increased IL-1β and IL-6 levels and microglia activation in the prefrontal cortex (PFC). In addition, mice exposed to LPS and CUS displayed significantly decreased PV expression and disturbance of theta and gamma oscillations in the PFC. However, chronic fluoxetine treatment reversed most of these abnormalities. Conclusion: Our study of this two-hit model of depression is clinically relevant and suggests the combination of different etiological and pathophysiological components of depression may provide with a more translational value.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

BACTERIAL ENDOTOXIN - A TRIGGER FACTOR FOR ALCOHOLIC PANCREATITIS (AP)? EVIDENCE FROM A NOVEL, PHYSIOLOGICALLY RELEVANT ANIMAL MODEL

Pancreas ◽  
2006 ◽  
Vol 33 (4) ◽  
pp. 506-507 ◽  
Author(s):  
A. Vonlaufen ◽  
Z. Xu ◽  
B. Daniel ◽  
S. Joshi ◽  
R. K. Kumar ◽  
...  
Keyword(s):  
Animal Model ◽  
Trigger Factor ◽  
Bacterial Endotoxin ◽  
Alcoholic Pancreatitis ◽  
Relevant Animal Model

Increase in neurogenesis and behavioural benefit after chronic fluoxetine treatment in Wistar rats

2007 ◽  
Vol 0 (0) ◽  
pp. 070905010742003-??? ◽  
Author(s):  
A. B. Marcussen ◽  
P. Flagstad ◽  
P. E. G. Kristjansen ◽  
F. F. Johansen ◽  
U. Englund
Keyword(s):  
Wistar Rats ◽  
Fluoxetine Treatment ◽  
Chronic Fluoxetine

scholarly journals Intrinsic hippocampal network activity is altered in MeCP2-deficient mice

2007 ◽  
Vol 8 (S2) ◽  
Author(s):  
Liang Zhang ◽  
Jiwei He ◽  
Denis GM Jugloff ◽  
James H Eubanks
Keyword(s):  
Network Activity ◽  
Hippocampal Network ◽  
Deficient Mice

scholarly journals The Developmental Role of Serotonin: A Comparison of Short- and Long-term Blockade of the Serotonin Transporter on Behavioural Outcomes in Adulthood

2021 ◽  
Author(s):  
◽  
Amy O'Connell
Keyword(s):  
Animal Model ◽  
Serotonin Transporter ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Critical Periods ◽  
Significant Group ◽  
Fluoxetine Treatment ◽  
Short And Long Term

<p>Serotonin is an important neurotransmitter that regulates a range of processes within the brain and is implicated in several psychiatric disorders. In addition, serotonin acts as a developmental signal during critical periods of prenatal development, influencing processes such as neuronal proliferation, migration, and synaptogenesis (Gaspar et al., 2003). The serotonin transporter (5- HTT) plays a key role in regulating extracellular serotonin levels and is the main target of selective-serotonin reuptake inhibitors (SSRIs), a class of drugs that have anti-anxiety and anti- depressive activity. SSRIs cause an acute increase in extracellular serotonin and are commonly prescribed as a treatment for depression and anxiety during pregnancy (Tran & Robb, 2015). Given that these drugs alter serotonin transmission and can pass to the developing fetus via the placenta, it is vital that the outcomes of prenatal SSRI exposure are investigated. In humans, a genetic variant of the gene that codes for the 5-HTT (SLC6A4) has been linked to increased risk for developing depression and anxiety (Caspi et al., 2003). The functional consequences of this genetic polymorphism are life-long alterations in 5-HTT activity, resulting in increased extracellular levels of serotonin (Nakamura et al., 2000). Given prenatal SSRI exposure results in a time-locked blockade of 5-HTT during critical periods of development, it follows that alterations in serotonin during development might similarly result in enhanced risk for depression and anxiety later in life. Outcomes in children prenatally exposed to SSRIs are difficult to study due to confounds of pre- existing maternal depression. Therefore, the current thesis presents two experiments that aimed to further investigate the role of altered extracellular serotonin levels during development in an animal model. Experiment one aimed to develop a method of voluntary oral administration of the SSRI fluoxetine to pregnant rat dams. This method was then applied in experiment two to create a time-locked blockade of 5-HTT during critical periods of development in an animal model of life-long 5-HTT blockade. The aim of experiment two was to directly assess the contribution of short- and long-term 5-HTT blockade on anxiety and depression phenotypes in adult male offspring. In addition, maternal behaviour was assessed to determine whether fluoxetine treatment had an influence on mother-pup interactions that could confound results. To test for anxiety and depression phenotypes, the novel affective disorder test (ADT) was used to assess anxiety behaviour and the deficits in anticipatory pleasure indicative of anhedonia. In the current study, fluoxetine treatment did not have an effect on litter outcomes or mother-pup interactions. Crucially, no significant group differences were found indicating that neither short- nor long- term blockade of 5-HTT resulted in increased anxiety- or depressive-like behaviours in the current experiment. However, limitations with methodological design limit the translatability of these results to the broader literature, and validation of the ADT is required before these results can be generalised beyond this thesis.</p>

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