Schizophrenia Hippocampus

N-methyl-D-aspartic acid receptors (NMDARs) are the most studied receptors in mammalian brains. Their role in depression, cognition, schizophrenia, learning and memorization, Alzheimer's disease, and more is well documented. In the search for new drug candidates in depression, intensive studies have been conducted. Compounds that act by influencing NMDARs have been particularly intensively investigated following the success of ketamine in clinics. Unfortunately, the side effects associated with ketamine do not allow it to be useful in all cases...

The MAP kinase ERK is important for neuronal plasticity underlying associative learning, yet specific molecular pathways for neuronal ERK activation are undetermined. RapGEF2 is a neuron-specific cAMP sensor that mediates ERK activation. We investigated whether it is required for cAMP-dependent ERK activation leading to other downstream neuronal signaling events occurring during associative learning, and if RapGEF2-dependent signaling impairments affect learned behavior. Camk2α-cre+/- ::RapGEF2fl/fl mice with depletion of RapGEF2 in hippocampus and amygdala exhibit impairments in context- and cue-dependent fear conditioning linked to corresponding impairment in Egr1 induction in these two brain regions...

BACKGROUND: Prenatal alcohol exposure (PAE) can result in reduced brain volume and an increased risk of mental health challenges. Limbic brain structures such as the hippocampus, thalamus, and amygdala often exhibit smaller volumes in youth with PAE, and similar volume reductions are observed in unexposed youth with symptoms of depression, bipolar disorder, anxiety, and schizophrenia. However, the role of volume reductions in these brain regions in mental health challenges remains unclear for individuals with PAE...

Genome-wide association studies (GWAS) have revealed the polygenic nature of treatment-resistant schizophrenia TRS. Gene expression imputation allowed the translation of GWAS results into regulatory mechanisms and the construction of gene expression (GReX) risk scores (GReX-RS).  In the present study we computed GReX-RS from the largest GWAS of TRS to assess its association with clinical features. We perform transcriptome imputation in the largest GWAS of TRS to find GReX associated with TRS using brain tissues...

The partial N-methyl-D-aspartate receptor (NMDAR) agonist D-Cycloserine (DCS) has been evaluated for the treatment of a wide variety of psychiatric disorders, including dementia, schizophrenia, depression and for the augmentation of exposure-based psychotherapy. Most if not all of the potential psychiatric applications of DCS target an enhancement or restitution of cognitive functions, learning and memory. Their molecular correlate is long-term synaptic plasticity; and many forms of synaptic plasticity depend on the activation of NMDA receptors...

BACKGROUND: Psychiatric disorders, such as schizophrenia, are complex and challenging to study, partly due to the lack of suitable animal models. However, the absence of the Slc10a4 gene, which codes for a monoaminergic and cholinergic associated vesicular transporter protein, in knockout mice (Slc10a4-/- ), leads to the accumulation of extracellular dopamine. A major challenge for studying schizophrenia is the lack of suitable animal models that accurately represent the disorder. We sought to overcome this challenge by using Slc10a4-/- mice as a potential model, considering their altered dopamine levels...

Dysfunction of the corticolimbic system, particularly at the dendritic spine level, is a recognized core mechanism in neurodevelopmental disorders such as schizophrenia. Neonatal ventral hippocampus lesion (NVHL) in Sprague-Dawley rats induces both a schizophrenia-related behavioral phenotype and dendritic spine pathology (reduced total number and mature spines) in corticolimbic areas, which is mitigated by antipsychotics. However, there is limited information on the impact of rat strain on NVHL outcomes and antipsychotic effects...

Phosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS...

BACKGROUND: Similarities among schizophrenia (SZ), schizoaffective disorder (SAD) and bipolar disorder (BP) including clinical phenotypes, brain alterations and risk genes, make it challenging to perform reliable separation among them. However, previous subtype identification that transcend traditional diagnostic boundaries were based on group-level neuroimaging features, ignoring individual-level inferences. METHODS: 455 psychoses (178 SZs, 134 SADs and 143 BPs), their first-degree relatives (N = 453) and healthy controls (HCs, N = 220) were collected from Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP I) consortium...

Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental trajectory. We aimed to investigate how SI affects the expression of genes in mouse hippocampus and to investigate how these changes related to the genetic basis of neurodevelopmental phenotypes. BL/6J mice were exposed to post-weaning SI (PD21-25) or treated as group-housed controls (n = 7-8 per group)...

In this issue, Griesius et al report that heterozygous Dlg2+/- rats showed a reversal learning impairment on a specific bowl-digging task, whereas other reversal tasks were unaffected. The study suggests that Dlg2 gene disruption, which has been linked to neuropsychiatric disorders, including schizophrenia, may cause relatively specific impairments in reversal learning, an important aspect of cognitive flexibility. The study draws attention to two important issues regarding the neuro-behavioral mechanisms of reversal learning, namely that hippocampal dysfunction, which is prominent in Dlg2+/- rats, may contribute to reversal learning impairments and that, depending on the task and previous experience, brain and behavioral mechanisms of reversal learning may differ...

The neuroinflammatory state may contribute to the pathogenesis of many mental disorders including schizophrenia. Nicotinamide adenine dinucleotide (NAD+ ) is an essential cofactor for activation of proteins involved in mitochondria quality control, such as Sirtuin3 (SIRT3). Our previous study has found that NAD+ supplement could rescue early life stress (ELS)-induced neuroinflammation and down-regulation of SIRT3 in adult offspring. However, it is unclear whether SIRT3 is the key to the neuroprotective effects of NAD+ supplement in this animal model of schizophrenia...

Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated receptor 1 (TAAR1) agonism has emerged as a potential new treatment approach for schizophrenia. While current evidence implicates TAAR1-mediated regulation of dopaminergic tone as the primary circuit mechanism, little is known about the effects of TAAR1 agonists on the glutamatergic system and excitation-inhibition balance...

The Roman high-avoidance (RHA) and low-avoidance (RLA) rat lines/strains were established in Rome through bidirectional selection of Wistar rats for rapid (RHA) or extremely poor (RLA) acquisition of a two-way active avoidance task. Relative to RHAs, RLA rats exhibit enhanced threat sensitivity, anxiety, fear and vulnerability to stress, a passive coping style and increased sensitivity to frustration. Thus, RLA rats' phenotypic profile falls well within the "internalizing" behavior spectrum. Compared with RLAs and other rat strains/stocks, RHAs present increased impulsivity and reward sensitivity, deficits in social behavior and attentional/cognitive processes, novelty-induced hyper-locomotion and vulnerability to psychostimulant sensitization and drug addiction...

Besides playing a central role in neuroinflammation, microglia regulate synaptic development and is involved in plasticity. Converging lines of evidence suggest that these different processes play a critical role in schizophrenia. Furthermore, previous studies reported altered transcription of microglia genes in schizophrenia, while microglia itself seems to be involved in the etiopathology of the disease. However, the regional specificity of these brain transcriptional abnormalities remains unclear. Moreover, it is unknown whether brain and peripheral expression of microglia genes are related...

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is a multifaceted mental disorder marked by a spectrum of symptoms, including hallucinations, delusions, cognitive deficits, and negative symptoms. Its etiology involves intricate interactions between genetic and environmental factors, posing significant challenges for effective treatment. We hypothesized that intranasal administration of exosomes derived from nasal olfactory mucosal mesenchymal stem cells (OM-MSCs-exos) could alleviate SCZ-like behaviors in a murine model induced by methylazoxymethanol (MAM)...

INTRODUCTION: Schizophrenia is a severe psychotic brain disorder. One of the potential mechanisms underlying this disease may be volumetric changes in some brain regions. The present study aimed to employ magnetic resonance imaging (MRI) to estimate and quantitatively analyze the brain of patients with schizophrenia compared to the controls. METHODS: This case-control study was conducted on MRI scans of 20 patients with schizophrenia and 20 healthy controls in Zahedan City, Southeastern Iran...

Background and Purpose P2X4 receptors (P2X4R) are ligand gated cation channels that are activated by extracellular adenosine 5'-triphosphate (ATP) released by neurons and glia. The receptors are widely expressed in the brain and have fractional calcium currents comparable to NMDA receptors. Although P2X4Rs were described to modulate synaptic transmission and plasticity, their involvement in shaping neuronal network activity remains to be elucidated. Exp. Approach We investigated the effects of P2X receptors on network and synaptic level using local field potential electrophysiology, whole cell patch clamp recordings and calcium imaging in fast spiking parvalbumin positive interneurons (PVINs) in rat and mice hippocampal slices...

Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid...

Abnormal processes of learning from prediction errors, i.e. the discrepancies between expectations and outcomes, are thought to underlie motivational impairments in schizophrenia. Although dopaminergic abnormalities in the mesocorticolimbic reward circuit have been found in patients with schizophrenia, the pathway through which prediction error signals are processed in schizophrenia has yet to be elucidated. To determine the neural correlates of prediction error processing in schizophrenia, we conducted a meta-analysis of whole-brain neuroimaging studies that investigated prediction error signal processing in schizophrenia patients and healthy controls...