Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin

Neuronal Signaling, Год журнала: 2023, Номер 7(2)

Опубликована: Июнь 26, 2023

Abstract There are several hypotheses concerning the underlying pathophysiological mechanisms of major depression, which centre largely around adaptive changes in neuronal transmission and plasticity, neurogenesis, circuit regional connectivity. The immune endocrine systems commonly implicated driving these changes. An intricate interaction stress hormones, innate cells actions soluble mediators immunity within nervous system is described as being associated with symptoms depression. Bridging processes to neurotransmission signalling key cortical limbic brain circuits critical understanding depression a disorder neuroimmune origins. Emergent areas research include growing recognition system, advances neuroimaging techniques mechanistic insights gained from transgenic animals. Elucidation glial–neuronal interactions providing additional avenues into promising research, development clinically relevant disease models discovery novel therapies. This narrative review focuses on molecular cellular that influenced by inflammation stress. aim this provide an overview our current origin, focusing neuroendocrine dysregulation pathophysiology. Advances lie pursuit biomarkers, potential biomarker signatures improve clinical outcomes yet be fully realised. Further investigations expand panels including integration neuroimaging, utilising individual stratify patients more homogenous subpopulations targeting for new treatment approaches will help address unmet need.

Язык: Английский

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Neurobiology and systems biology of stress resilience

Physiological Reviews, Год журнала: 2024, Номер 104(3), С. 1205 - 1263

Опубликована: Март 14, 2024

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts unravel factors and mechanisms make possible harness its insights for development of preventative interventions in individuals at risk acquiring stress-related dysfunctions. Biological has been lagging behind psychological social sciences but seen a massive surge recent years. At same time, progress this field hampered methodological challenges related finding suitable operationalizations study designs, replicating findings, modeling animals. We embed review behavioral, neuroimaging, neurobiological, systems biological findings adults critical methods discussion. find preliminary evidence hippocampus-based pattern separation prefrontal-based cognitive control functions protect against pathological fears aftermath singular, event-type stressors [as found fear-related disorders, including simpler forms posttraumatic stress disorder (PTSD)] facilitating perception safety. Reward system-based pursuit savoring positive reinforcers appear more generalized dysfunctions anxious-depressive spectrum resulting from severe longer-lasting (as depression, comorbid anxiety, PTSD). Links between preserved functioning these neural under neuroplasticity, immunoregulation, gut microbiome composition, integrity barrier blood-brain are beginning emerge. On basis, avenues pointed out.

Язык: Английский

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Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma

Neuropsychopharmacology, Год журнала: 2016, Номер 41(11), С. 2749 - 2758

Опубликована: Июнь 9, 2016

Язык: Английский

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The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response

Current Molecular Pharmacology, Год журнала: 2017, Номер 11(1)

Опубликована: Март 6, 2017

Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is major physiological activator hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator mammalian response. Together with its three family members, urocortins (UCNs) 1, 2, 3, CRF integrates neuroendocrine, autonomic, metabolic behavioral responses to activating cognate receptors CRFR1 CRFR2.Here we review past current state CRF/CRFR field, ranging from pharmacological studies mouse models virus-mediated manipulations.Although it well established that CRF/CRFR1 signaling mediates aversive responses, including anxiety depression-like behaviors, number recent have challenged this viewpoint revealing anxiolytic appetitive properties specific circuits. In contrast, UCN/CRFR2 system less understood may possibly also exert divergent functions on physiology behavior depending brain region, underlying circuit, experienced conditions.A plethora available tools, conventional conditional mutants targeting components, has greatly advanced our understanding about endogenous mechanisms HPA regulation CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, detailed pathways molecular which CRF/UCN-system translates negative or positive stimuli into final, integrated biological response are not completely understood. The utilization future complementary methodologies, such as cell-type Cre-driver lines, viral optogenetic tools will help further dissect function genetically defined CRF/UCN neurocircuits context adaptive maladaptive responses.

Язык: Английский

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Modeling psychiatric disorders for developing effective treatments

Nature Medicine, Год журнала: 2015, Номер 21(9), С. 979 - 988

Опубликована: Сен. 1, 2015

Язык: Английский

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