Reduced White Matter Damage and Lower Neuroinflammatory Potential of Microglia and Macrophages in Hri/Eif2ak1 Mice After Contusive Spinal Cord Injury.

Cellular stressors inhibit general protein synthesis while upregulating stress response transcripts and/or proteins. Phosphorylation of the translation factor eIF2α by one of the several stress-activated kinases is a trigger for such signaling, known as the integrated stress response (ISR). The ISR regulates cell survival and function under stress.

Increased Incidence of Depression and Chronic Pain in Traumatic Spinal Cord Injury Patients With Pre-Injury Alcohol Use Disorder: Longitudinal Analysis of Insurance Claim Database.

Alcohol use disorder (AUD) increases risk of traumatic spinal cord injury (SCI) and is associated with depression, anxiety, and chronic pain. Given that these neuropsychiatric morbidities are frequently observed in SCI patients, the effects of pre-injury AUD on risk of depression, anxiety, or chronic pain were analyzed using an insurance claim database. Of 10,591 traumatic SCI patients, 507 had AUD-associated claims in a 12-month period before injury.

Opposite modulation of functional recovery following contusive spinal cord injury in mice with oligodendrocyte-selective deletions of Atf4 and Chop/Ddit3.

The integrated stress response (ISR)-activated transcription factors ATF4 and CHOP/DDIT3 may regulate oligodendrocyte (OL) survival, tissue damage and functional impairment/recovery in white matter pathologies, including traumatic spinal cord injury (SCI). Accordingly, in OLs of OL-specific RiboTag mice, Atf4, Chop/Ddit3 and their downstream target gene transcripts were acutely upregulated at 2, but not 10, days post-contusive T9 SCI coinciding with maximal loss of spinal cord tissue. Unexpectedly, another, OL-specific upregulation of Atf4/Chop followed at 42 days post-injury.

Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle.

Introduction: Sex and ovarian hormones influence cocaine seeking and relapse vulnerability, but less is known regarding the cellular and synaptic mechanisms contributing to these behavioral sex differences. One factor thought to influence cue-induced seeking behavior following withdrawal is cocaine-induced changes in the spontaneous activity of pyramidal neurons in the basolateral amygdala (BLA). However, the mechanisms underlying these changes, including potential sex or estrous cycle effects, are unknown.

Fine particulate matter (PM) inhalation-induced alterations in the plasma lipidome as promoters of vascular inflammation and insulin resistance.

Fine particulate matter (PM) air pollution exposure increases the risk of developing cardiovascular disease (CVD). Although the precise mechanisms by which air pollution exposure increases CVD risk remain uncertain, research indicates that PM-induced endothelial dysfunction contributes to CVD risk. Previous studies demonstrate that concentrated ambient PM (CAP) exposure induces vascular inflammation and impairs insulin and vascular endothelial growth factor (VEGF) signaling dependent on pulmonary oxidative stress.

Sex-Specific Role for Dopamine Receptor D2 in Dorsal Raphe Serotonergic Neuron Modulation of Defensive Acoustic Startle and Dominance Behavior.

Brain networks underlying states of social and sensory alertness are normally adaptive, influenced by serotonin and dopamine (DA), and abnormal in neuropsychiatric disorders, often with sex-specific manifestations. Underlying circuits, cells, and molecules are just beginning to be delineated. Implicated is a subtype of serotonergic neuron denoted , distinguished by expression of the type-2 DA receptor () gene, inhibited cell-autonomously by DRD2 agonism in slice, and, when constitutively silenced in male mice, affects levels of defensive and exploratory behaviors (Niederkofler et al.

Mitochondria-associated lactate dehydrogenase is not a biologically significant contributor to bioenergetic function in murine striated muscle.

Previous studies indicate that mitochondria-localized lactate dehydrogenase (mLDH) might be a significant contributor to metabolism. In the heart, the presence of mLDH could provide cardiac mitochondria with a higher capacity to generate reducing equivalents directly available for respiration, especially during exercise when circulating lactate levels are high. The purpose of this study was to test the hypothesis that mLDH contributes to striated muscle bioenergetic function.

Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior.

Escalated aggression can have devastating societal consequences, yet underlying neurobiological mechanisms are poorly understood. Here, we show significantly increased inter-male mouse aggression when neurotransmission is constitutively blocked from either of two subsets of serotonergic, Pet1 neurons: one identified by dopamine receptor D1(Drd1a)::cre-driven activity perinatally, and the other by Drd2::cre from pre-adolescence onward. Blocking neurotransmission from other Pet1 neuron subsets of similar size and/or overlapping anatomical domains had no effect on aggression compared with controls, suggesting subtype-specific serotonergic neuron influences on aggression.

Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.

Unlabelled: Newborn neurons enter an extended maturation stage, during which they acquire excitability characteristics crucial for development of presynaptic and postsynaptic connectivity. In contrast to earlier specification programs, little is known about the regulatory mechanisms that control neuronal maturation. The Pet-1 ETS (E26 transformation-specific) factor is continuously expressed in serotonin (5-HT) neurons and initially acts in postmitotic precursors to control acquisition of 5-HT transmitter identity.

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons.

Dorsal raphe serotonin neurons in mice: immature hyperexcitability transitions to adult state during first three postnatal weeks suggesting sensitive period for environmental perturbation.

Trauma during early life is a major risk factor for the development of anxiety disorders and suggests that the developing brain may be particularly sensitive to perturbation. Increased vulnerability most likely involves altering neural circuits involved in emotional regulation. The role of serotonin in emotional regulation is well established, but little is known about the postnatal development of the raphe where serotonin is made.

Site of origin of and sex differences in the vasopressin innervation of the mouse (Mus musculus) brain.

Defining how arginine vasopressin (AVP) acts centrally to regulate homeostasis and behavior is problematic, as AVP is made in multiple nuclei in the hypothalamus (i.e., paraventricular [PVN], supraoptic [SON], and suprachiasmatic [SCN]) and extended amygdala (i.

Vasopressin innervation of the mouse (Mus musculus) brain and spinal cord.

The neuropeptide vasopressin (AVP) has been implicated in the regulation of numerous physiological and behavioral processes. Although mice have become an important model for studying this regulation, there is no comprehensive description of AVP distribution in the mouse brain and spinal cord. With C57BL/6 mice, we used immunohistochemistry to corroborate the location of AVP-containing cells and to define the location of AVP-containing fibers throughout the mouse central nervous system.

Unexpected effects of perinatal gonadal hormone manipulations on sexual differentiation of the extrahypothalamic arginine-vasopressin system in prairie voles.

The sexually dimorphic extrahypothalamic arginine-vasopressin (AVP) projections from the bed nucleus of the stria terminalis to the lateral septum (LS) and lateral habenula (LHb) are denser in males than females and, in rats, require males' perinatal exposure to gonadal hormones but the absence of such exposure in females. We examined perinatal hormone effects on development of this sex difference in prairie voles (Microtus ochrogaster), which show atypical effects of hormones on sexual differentiation of some reproductive behaviors. Neonatal castration reduced the number of AVP mRNA-expressing cells in the bed nucleus of the stria terminalis and AVP immunoreactivity (ir) in the LS and LHb.

Parental responsiveness is feminized after neonatal castration in virgin male prairie voles, but is not masculinized by perinatal testosterone in virgin females.

We previously found a large sex difference in the parental responsiveness of adult virgin prairie voles (Microtus ochrogaster) such that most males are spontaneously parental, whereas most females are not. Because this sex difference is independent of the gonadal hormones normally circulating in adult virgin voles, the present study examined whether perinatal hormones influence the development of this sex difference. Males were treated prenatally (via their pregnant dam) with both the androgen receptor blocker flutamide (5 mg/day/dam) and the aromatase inhibitor ATD (1 mg/day/dam), or oil, for the last 2 weeks of gestation.