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Understanding the pathophysiological mechanisms of neuropsychiatric disorders has been a challenging quest for neurobiologists. Recent years have witnessed enormous technological advances in the field of neuroimmunology, blurring boundaries between the central nervous system and the periphery. Consequently, the discipline has expanded to cover interactions between the nervous and immune systems in health and diseases. The complex interplay between the peripheral and central immune pathways in neuropsychiatric disorders has recently been documented in various studies, but the genetic determinants remain elusive. Recent transcriptome studies have identified dysregulated genes involved in peripheral immune cell activation, blood-brain barrier integrity, glial cell activation, and synaptic plasticity in major depressive disorder, bipolar disorder, autism spectrum disorder, and schizophrenia. Herein, the key transcriptomic techniques applied in investigating differentially expressed genes and pathways responsible for altered brain-immune interactions in neuropsychiatric disorders are discussed. The application of transcriptomics that can aid in identifying molecular targets in various neuropsychiatric disorders is highlighted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The female brain is highly dynamic and can fundamentally remodel throughout the normal ovarian cycle as well as in critical life stages including perinatal development, pregnancy and old-age. As such, females are particularly vulnerable to infections, psychological disorders, certain cancers, and cognitive impairments. We will present the latest evidence on the female brain; how it develops through the neonatal period; how it changes through the ovarian cycle in normal individuals; how it adapts to pregnancy and postpartum; how it responds to illness and disease, particularly cancer; and, finally, how it is shaped by old age. Throughout, we will highlight female vulnerability to and resilience against disease and dysfunction in the face of environmental challenges., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Data from clinical and preclinical studies indicate that immune dysregulation, specifically of inflammatory processes, is associated with symptoms of major depressive disorder (MDD). In particular, increased levels of circulating pro-inflammatory cytokines and concomitant activation of brain-resident microglia can lead to depressive behavioural symptoms. Repeated exposure to psychological stress has a profound impact on peripheral immune responses and perturbs the function of brain microglia, which may contribute to neurobiological changes underlying MDD. Here, we review these findings and discuss ongoing studies examining neuroimmune mechanisms that influence neuronal activity as well as synaptic plasticity. Interventions targeting immune-related cellular and molecular pathways may benefit subsets of MDD patients with immune dysregulation.

To successfully treat Alzheimer's disease (AD), pathophysiological events in preclinical stages need to be identified. Preclinical AD refers to the stages that exhibit amyloid deposition in the brain but have normal cognitive function, which are replicated in young adult APPswe/PS1deltaE9 (deltaE9) mice. By long-term in vivo two-photon microscopy, we demonstrate impaired adaptive spine plasticity in these transgenic mice illustrated by their failure to increase dendritic spine density and form novel neural connections when housed in enriched environment (EE). Decrease of amyloid plaques by reducing BACE1 activity restores the gain of spine density upon EE in deltaE9 mice, but not the remodeling of neural networks. On the other hand, anti-inflammatory treatment with pioglitazone or interleukin 1 receptor antagonist in deltaE9 mice successfully rescues the impairments in increasing spine density and remodeling of neural networks during EE. Our data suggest that neuroinflammation disrupts experience-dependent structural plasticity of dendritic spines in preclinical stages of AD.

Homeostatic synaptic plasticity refers to a set of negative-feedback mechanisms that are used by neurons to maintain activity within a functional range. While it is becoming increasingly clear that homeostatic regulation of synapse function is a key principle in the nervous system, the molecular details of this regulation are only beginning to be uncovered. Recent evidence implicates molecules classically associated with the peripheral immune system in the modulation of homeostatic synaptic plasticity. In particular, the pro-inflammatory cytokine TNFα, class I major histocompatibility complex, and neuronal pentraxin 2 are essential in the regulation of the compensatory synaptic response that occurs in response to prolonged neuronal inactivity. This review will present and discuss current evidence implicating neuroimmune molecules in the homeostatic regulation of synapse function. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Chronic neuropathic and inflammatory pain is a major public health problem. Nociceptors undergo sensitization, first in peripheral tissues then in the central nervous sytem, via neuroimmune interactions linking neurons, glial cells (microglia and astrocytes), and immune cells. These interactions may either exacerbate or attenuate the pain and inflammation, which normally reach a state of equilibrium. With more powerful or longer lasting stimuli, specific profiles of microglial and, subsequently, astrocytic activation in the dorsal horn play a key role in neuronal plasticity and transition to chronic pain. Recent insights into the interactions between the nervous system and the immune system suggest a large number of potential therapeutic targets that could be influenced either by targeted inhibition or by directing the neuroimmune response toward the antiinflammatory and analgesic end of its spectrum., (Copyright © 2011. Published by Elsevier SAS.)

The presence and function of immune molecules in the central nervous system (CNS) have been under debate for a long time. There is mounting evidence that molecules fundamental for immune function are indeed expressed by both neurons and glia and that such molecules may have important nonimmunological function for the organization and stability of synaptic connections. Here, we present data showing that the classic form of major histocompatibility complex (MHC) class I molecules is expressed in spinal motoneurons, in particular in their axons and presynaptically at their synapses with skeletal muscles, the neuromuscular junctions (NMJs). The expression is strongly increased after axon lesion in the peripheral nerve. In the absence of classic MHC I, the organization of NMJs is disturbed with NMJs in higher numbers than normal, thereby equipping single muscle fibers with multiple NMJs. It is suggested that these effects are mediated by the classic MHC class I in the motor axons, possibly through effects mediated by the peripherally myelinating Schwann cells, which express receptors for classic MHC class I. The presence of immune molecules normally used by other cells for antigen presentation in peripheral motor axons may have implications for the onset of specific motoneuron disease.

An increasing number of studies support an unexpected role for immune molecules in regulating healthy brain functions during development and in adulthood. Here we review the roles of specific immune molecules (including cytokines, components of the complement cascade, and members of the major histocompatibility complex class I family and their receptors) in the formation and plasticity of glutamatergic synapses. These findings add a new dimension to our understanding of neural-immune interactions, and suggest novel molecular mechanisms that may underlie the modification of glutamatergic synapses in both normal and pathological states., (© The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Parallel advances in neuroscience and immunology established the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. Like other physiological systems, the immune system--and the development of immunity--is modulated by neural reflexes. A prototypical example is the inflammatory reflex, comprised of an afferent arm that senses inflammation and an efferent arm, the cholinergic anti-inflammatory pathway, that inhibits innate immune responses. This mechanism is dependent on the alpha7 subunit of the nicotinic acetylcholine receptor, which inhibits NF-kappaB nuclear translocation and suppresses cytokine release by monocytes and macrophages. Here we summarize evidence showing that innate immunity is reflexive. Future advances will come from applying an integrative physiology approach that utilizes methods adapted from neuroscience and immunology.

In contrast to other organs where the tissue is capable of replacing lost cells and thus regaining tissue function, immune cell recruitment and activation is suppressed in the CNS in order to minimize secondary damage after lesion. This state of immune privilege has its cost because the injured tissue cannot fully benefit from growth-promoting effects accompanying inflammatory responses. These responses include phagocytosis of growth-inhibiting myelin debris by cells of the innate immune system and the recently described protection of surviving fibers by myelin-specifie T cells of the adaptive immune system. While the signals suppressing macrophage functions in the CNS are yet to be defined, it seems that help from T cells is diminished by apoptosis-induction via death-inducing ligands. Indeed, the death ligand CD95L (FasL, APO 1 L) is constitutively found on neurons, microglia and astrocytes. Its upregulation on astrocytes during axonal degeneration in the hippocampus after entorhinal lesion is accompanied by the appearance of apoptotic leukocytes. T cells also express CD95L and TNF-related apoptosis- inducing ligand (TRAIL), and the presence of CD95 (Fas, APOI) and TRAIL-receptors renders brain cells putative targets of T cell-induced apoptosis. Thus, blockade of death ligands could be helpful by simultaneously enhancing T cell survival and blocking T cell-mediated brain cell death. This is only one example of how boosting helpful immune cell functions and abrogating their destructive effects might help to overcome the brain's failure to regenerate after axonal lesions.

In experiments on mature and developing (3-4 weeks old) rats the influence was shown of neuroimmunization with summate antigens of hippocampal or neocortical tissue cytosolic fraction on short-term plasticity of hippocampal CA3 field potentials under dentate gyrus zone stimulation. An increase of paired facilitation and frequency potentiation was revealed in pyramidal layer responses of hippocampal tissue immunized animals. In case of immunization with neocortical antigens the changes were less expressed, had mainly the opposite direction and took place in the apical dendrites zone. In young animals besides antigen spectrum depending effects of neuroimmunization an earlier manifestation (in comparison with age norm) of some focal activity definitive properties was described. The suggestions are made about different localization of hippocampal or neocortical tissue immunization "targets" with possible preferential damage of intrahippocampal systems when using this structure antigens, and also about dependence of physiological consequences on the extent of target structure ontogenetic maturity.