Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats

Sang-Chan Jeon,Hye-Ji Kim,Eun-A Ko,Sung-Cherl Jung 한국뇌신경과학회 2021 Experimental Neurobiology Vol.30 No.1

High levels of cortisol in blood are frequently observed in patients with major depressive disorders and increased cortisol level induces depressivelike symptoms in animal models. However, it is still unclear whether maternal cortisol level during pregnancy is a critical factor resulting in neuropsychiatric disorders in offspring. In this study, we increased cortisol level in rats by repetitively injecting corticosterone subcutaneously (Corti. Mom, 20 mg/kg/day) during pregnancy and evaluated the behavioral patterns of their pups (Corti.Pups) via forced swimming (FS), open field (OF), elevated plus maze (EPM) and Morris water maze (MWM) tests during the immediate post-weaning period (postnatal day 21 to 25). In results, corticosterone significantly increased plasma cortisol levels in both Corti.Moms and Corti.Pups. Unlike depressive animal models, Corti.Pups showed higher hyperactive behaviors in the FS and OF tests than normal pups (Nor.Pups) born from rats (Nor.Moms) treated with saline. Furthermore, Corti.Pups spent more time and traveled longer distance in the open arms of EPM test, exhibiting higher extremity. These patterns were consistent with behavioral symptoms observed in animal models of attention deficit hyperactivity disorder (ADHD), which is characterized by hyperactivity, impulsivity, and inattention. Additionally, Corti.Pups swam longer and farther to escape in MWM test, showing cognitive declines associated with attention deficit. Our findings provide evidence that maternal cortisol level during pregnancy may affect the neuroendocrine regulation and the brain development of offspring, resulting in heterogeneous developmental brain disorders such as ADHD.

Negative Influence of the Hunger State on Rule-observance Behavior in Mice

Abdelrahman M. Alkahwaji,신희섭,이창준 한국뇌신경과학회 2023 Experimental Neurobiology Vol.32 No.1

Developing social strategies to share limited resources equally and maximize the long-term benefits of conflict resolution is critical for appropriate social interactions. During social interactions, social decision-making depends not only on the external environment, but also on internal factors, such as hunger, thirst, or fatigue. In particular, hunger, which is related to food as a physical need, plays a dominant role in social decision-making. However, the consequences of food deprivation on social decision-making are not well understood. We have previously shown that mice with rule-observance behavior are capable of resolving conflict during social decision-making by observing a well-established social strategy based on reward zone allocation. Here, we developed a rule-observance behavior paradigm wherein the hunger state is achieved by applying food restric- tions on mice prior to social behavior experiments.We found that the hunger state in mice deteriorated the established social strategy by decreasing reaction time, implying an increase in impulsivity. In contrast, the hunger state did not affect reward zone allocation, indicating no effect on spatial memory. This decrease in reaction time led to a significant increase in the percentage of violations during rule observance and a significant de- crease in the amount of reward (payoff equity). Our study proposes that the hunger state exerts a detrimental effect on appropriate social decision- making by decreasing reaction time, increasing violation, and decreasing payoff equity in rule-observance behavior.

Comparison between Flail Arm Syndrome and Upper Limb Onset Amyotrophic Lateral Sclerosis: Clinical Features and Electromyographic Findings

윤병남,최성혜,나정호,강사윤,이광우,성정준 한국뇌신경과학회 2014 Experimental Neurobiology Vol.23 No.3

Flail arm syndrome (FAS), an atypical presentation of amyotrophic lateral sclerosis (ALS), is characterized by progressive,predominantly proximal, weakness of upper limbs, without involvement of the lower limb, bulbar, or respiratory muscles. Whenencountering a patient who presents with this symptomatic profile, possible diagnoses include upper limb onset ALS (UL-ALS), andFAS. The lack of information regarding FAS may make differential diagnosis between FAS and UL-ALS difficult in clinical settings. The aim of this study was to compare clinical and electromyographic findings from patients diagnosed with FAS with those frompatients diagnosed with UL-ALS. To accomplish this, 18 patients with FAS and 56 patients with UL-ALS were examined. Significantdifferences were observed between the 2 groups pertaining to the rate of fasciculation, patterns of predominantly affected muscles,and the Medical Research Council scale of the weakest muscle. The presence of upper motor neuron signs and lower motor neuroninvolvement evidenced through electromyography showed no significant between-group differences.

A Short Review on the Current Understanding of Autism Spectrum Disorders

박혜란,이재민,문효은,이동수,김붕년,김진현,김동규,백선하 한국뇌신경과학회 2016 Experimental Neurobiology Vol.25 No.1

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo- cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.

Drug Abuse and Psychosis: New Insights into Drug-induced Psychosis

함수지,임혜인,김태규,정수영 한국뇌신경과학회 2017 Experimental Neurobiology Vol.26 No.1

Addictive drug use or prescribed medicine abuse can cause psychosis. Some representative symptoms frequently elicited by patients with psychosis are hallucination, anhedonia, and disrupted executive functions. These psychoses are categorized into three classifications of symptoms: positive, negative, and cognitive. The symptoms of DIP are not different from the symptoms of schizophrenia, and it is difficult to distinguish between them. Due to this ambiguity of distinction between the DIP and schizophrenia, the DIP animal model has been frequently used as the schizophrenia animal model. However, although the symptoms may be the same, its causes are clearly different in that DIP is acquired and schizophrenia is heritable. Therefore, in this review, we cover several DIP models such as of amphetamine, PCP/ketamine, scopolamine, and LSD, and then we also address three schizophrenia models through a genetic approach with a new perspective that distinguishes DIP from schizophrenia.

Neurochemical Properties of Dental Primary Aff erent Neurons

Hue Vang,정지훈,김현영,박석범,정승준,김중수,오석배 한국뇌신경과학회 2012 Experimental Neurobiology Vol.21 No.2

The long belief that dental primary afferent (DPA) neurons are entirely composed of nociceptive neurons has been challenged by several anatomical and functional investigations. In order to characterize non-nociceptivepopulation among DPA neurons,retrograde transport fluorescent dye was placed in upper molars of rats and immunohistochemical detection of peripherin and neurofilament 200 in the labeled trigeminal ganglia was performed. As the results, majority ofDPA neurons were peripherinexpressing small-sized neurons, showing characteristic ofnociceptive C-fi bers. However, 25.7% of DPA were stained with antibody against neurofi lament 200, indicating signifi cant portion of DPA neurons are related to large myelinated Aβ fi bers. Th ere were a small number of neurons thatexpressed both peripherin and neurofilament 200, suggestive of Aδ fibers. The possible transition of neurochemical properties by neuronal injury induced by retrograde labeling technique was ruled out by detection of minimal expression of neuronal injury marker, ATF-3. These results suggest that in addition to the large population of C-fiber-related nociceptive neurons, a subset of DPA neurons is myelinated large neurons,which is related to low-threshold mechanosensitive Aβfi bers. We suggest that these Aβ fi ber-related neurons might play a role as mechanotransducers of fl uid movement within dentinal tubules.

New Perspectives of Dyrk1A Role in Neurogenesis and Neuropathologic Features of Down Syndrome

박중규,정광철 한국뇌신경과학회 2013 Experimental Neurobiology Vol.22 No.4

Down syndrome (DS) is one of the most common genetic disorders accompanying with mental retardation, cognitive impairment,and deficits in learning and memory. The brains with DS also display many neuropathological features including alteration inneurogenesis and synaptogenesis and early onset of Alzheimer’s disease (AD)-like symptoms. Triplication of all or a part of humanchromosome 21, especially the 21q22.1~21q22.3 region called ‘Down syndrome critical region (DSCR)’, has been considered asthe main cause of DS. One gene product of DSCR, dual-specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A), hasbeen highlighted as a key contributor to the neural consequences of DS. This minireview summarizes accumulating recent reportsabout Dyrk1A involvement in the neuritogenesis, synaptogenesis, and AD-like neurofibrillary tangle formation, which is mainlyfocusing on Dyrk1A-mediated regulation of cytoskeletal proteins, such as tubulin, actin, and microtubule-associated protein tau. Understanding the molecular mechanisms of these phenomena may provide us a rational for new preventive and therapeutictreatment of DS.

New Therapeutic Options for Autism Spectrum Disorder: Experimental Evidences

Olga Peñagarikano 한국뇌신경과학회 2015 Experimental Neurobiology Vol.24 No.4

Autism spectrum disorder (ASD) is characterized by impairment in two behavioral domains: social interaction/communication together with the presence of stereotyped behaviors and restricted interests. The heterogeneity in the phenotype among patients and the complex etiology of the disorder have long impeded the advancement of the development of successful pharmacotherapies. However, in the recent years, the integration of findings of multiple levels of research, from human genetics to mouse models, have made considerable progress towards the understanding of ASD pathophysiology, allowing the development of more effective targeted drug therapies. The present review discusses the current state of pharmacological research in ASD based on the emerging common pathophysiology signature.

Differential Encoding of Trace and Delay Fear Memory in the Entorhinal Cortex

공미선,김남수,김성필,최준식 한국뇌신경과학회 2023 Experimental Neurobiology Vol.32 No.1

Trace fear conditioning is characterized by a stimulus-free trace interval (TI) between the conditioned stimulus (CS) and the unconditioned stimu- lus (US), which requires an array of brain structures to support the formation and storage of associative memory. The entorhinal cortex (EC) has been proposed to provide essential neural code for resolving temporal discontinuity in conjunction with the hippocampus. However, how the CS and TI are encoded at the neuronal level in the EC is not clear. In Exp. 1, we tested the effect of bilateral pre-training electrolytic lesions of EC on trace vs. delay fear conditioning using rats as subjects. We found that the lesions impaired the acquisition of trace but not delay fear conditioning confirming that EC is a critical brain area for trace fear memory formation. In Exp. 2, single-unit activities from EC were recorded during the pre- training baseline and post-training retention sessions following trace or delay conditioning. The recording results showed that a significant propor- tion of the EC neurons modulated their firing during TI after the trace conditioning, but not after the delay fear conditioning. Further analysis re- vealed that the majority of modulated units decreased the firing rate during the TI or the CS. Taken together, these results suggest that EC critically contributes to trace fear conditioning by modulating neuronal activity during the TI to facilitate the association between the CS and US across a temporal gap.

Mammalian Molecular Clocks

권일민,최한경,손기훈,김경진 한국뇌신경과학회 2011 Experimental Neurobiology Vol.20 No.1

As a consequence of the Earth's rotation, almost all organisms experience day and night cycles within a 24-hr period. To adapt and synchronize biological rhythms to external daily cycles, organisms have evolved an internal time-keeping system. In mammals, the master circadian pacemaker residing in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus generates circadian rhythmicity and orchestrates numerous subsidiary local clocks in other regions of the brain and peripheral tissues. Regardless of their locations, these circadian clocks are cell-autonomous and self- sustainable, implicating rhythmic oscillations in a variety of biochemical and metabolic processes. A group of core clock genes provides interlocking molecular feedback loops that drive the circadian rhythm even at the single-cell level. In addition to the core transcription/translation feedback loops, post-translational modifications also contribute to the fine regulation of molecular circadian clocks. In this article, we briefly review the molecular mechanisms and post-translational modifications of mammalian circadian clock regulation. We also discuss the organization of and communication between central and peripheral circadian oscillators of the mammalian circadian clock.