scholarly journals Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice

2020 ◽  
Author(s):  
Attilio Iemolo ◽  
Aisha Nur ◽  
Patricia Montilla-Perez ◽  
Victoria B Risbrough ◽  
Francesca Telese
Keyword(s):  
Psychiatric Disorders ◽  
Emotional Reactivity ◽  
Lateral Septum ◽  
Early Gene ◽  
Novelty Seeking ◽  
Behavioral Abnormalities ◽  
Specific Manner ◽  
The Brain ◽  
Adolescent Exposure

AbstractHeavy and frequent use of cannabis during adolescence increases the risk of developing psychiatric disorders. However, the neurobiological mechanisms underlying this vulnerability remain largely unknown. Here, we explore whether adolescent vulnerability to long-term behavioral effects of cannabis is modulated by Reelin, a gene implicated in the development of the brain and of psychiatric disorders. To this aim, heterozygous Reeler (HR) mice, that express reduced level of Reelin, were chronically exposed during adolescence to high doses (10mg/kg) of Δ9-tetrahydrocannabinol (THC), a major psychoactive component of cannabis. Mice were tested in early adulthood with multiple behavioral assays, including working memory, social interaction, locomotor activity, anxiety-like responses, stress reactivity, and pre-pulse inhibition. Compared to wild-type (WT), HR mice treated with THC showed impaired social behaviors, elevated disinhibitory phenotypes and increased responsiveness to aversive situations, in a sex-specific manner. Independent of THC exposure, HR mice also spent more time exploring unfamiliar objects, indicating that Reelin modulates novelty seeking behavior. To identify the neuronal ensemble underlying this elevated novelty seeking in HR mice, we mapped the regional brain expression of the immediate early gene, Fos, in mice exposed to novel objects. HR mice exhibited reduced neuronal activation in the lateral septum, a subcortical brain structure implicated in emotions, cognition and reward processes. Overall, these findings show that (1) Reelin deficiency influences behavioral abnormalities caused by heavy consumption of THC during adolescence, and (2) that Reelin plays a role in the neurobiological mechanisms underlying disinhibitory behaviors, such as novelty seeking.Significant StatementThe link between cannabis abuse and the development psychiatric disorders, especially in adolescents, makes understanding the neurobiological mechanisms underlying cannabis effects on the brain a significant biomedical problem. Reelin is a key signaling molecule in the development of the adolescent brain and of psychiatric disorders, but its role in modulating the behavioral changes induced by cannabis remain unknown. Here, we report an interaction between Reelin deficiency and chronic adolescent exposure to THC, a major psychoactive component of cannabis. This interaction led to cognitive deficits, disinhibitory behaviors and altered emotional reactivity in mice, in a sex-specific manner. These experiments are the first to establish a link between Reelin signaling and the endocannabinoid system targeted by THC.

Exogenous L-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice

2020 ◽  
Author(s):  
Adam J. Lundquist ◽  
Tyler J. Gallagher ◽  
Giselle M. Petzinger ◽  
Michael W. Jakowec
Keyword(s):  
Motor Behavior ◽  
Early Gene ◽  
Specific Gene ◽  
Motor Circuits ◽  
Specific Manner ◽  
Primary Astrocytes ◽  
Exercise Induced ◽  
The Brain

AbstractL-lactate is an energetic and signaling molecule that is key to the metabolic and neuroplastic connection between astrocytes and neurons and may be involved in exercise-induced neuroplasticity. This study sought to explore the role of L-lactate in astrocyte reactivity and neuroplasticity. Using in vitro cultures of primary astrocytes, we show L-lactate increased expression of plasticity-related genes, including neurotrophic factors, Bdnf, Gdnf, Cntf and the immediate early gene cFos. L-lactate’s promotion of neurotrophic factor expression may be mediated in part by the lactate receptor HCAR1 since application of the HCAR1 agonist 3,5-DHBA also increased expression of Bdnf in primary astrocytes. In vivo L-lactate administration to healthy mice caused a similar increase in the expression of plasticity-related genes as well as increased astrocyte morphological complexity in a region-specific manner, with increased astrocytic response found in the striatum but not the ectorhinal cortex, regions of the brain where increases in regional cerebral blood flow are increased or unaltered, respectively, with motor behavior. Additionally, L-lactate administration did not cause synaptogenesis or improve motor behavior based on the latency to fall on the accelerating rotarod, suggesting that L-lactate administration can initiate astrocyte-specific gene expression, but the activation of motor circuits is necessary to initiate striatal neuroplasticity. These results suggest that peripheral L-lactate is likely an important molecular component of exercise-induced neuroplasticity by acting in an astrocyte-specific manner to prime the brain for neuroplasticity.

Neuroplasticity and Psychiatry

1998 ◽  
Vol 32 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Bruce D. Gynther ◽  
Mike B. Calford ◽  
Pankaj Sah
Keyword(s):  
Psychiatric Disorder ◽  
Psychiatric Disorders ◽  
Neural Development ◽  
Critical Period ◽  
Clinical Observation ◽  
Aggressive Treatment ◽  
Long Term Changes ◽  
Activity Dependent ◽  
The Brain

Objective: There is increasing concern that the course of psychiatric disorders may be affected by parameters such as the duration and intensity of symptoms of initial episodes of illness. As this indicates that abnormal function produces long-term changes within the brain, a review of the neuroscience literature regarding neuroplasticity is warranted. Method: This article is a selective review, focusing in particular on results obtained from physiological experiments assessing plasticity within the mammalian neocortex. The possible relevance of results to psychiatry is discussed. Results: While the most dramatic examples of neuroplasticity occur during a critical period of neural development, neuroplasticity can also occur in adult neocortex. Neuroplasticity appears to be activity-dependent: synaptic pathways that are intensively used may become strengthened, and conversely, there may be depression of transmission in infrequently used pathways. Conclusions: Results from neurophysiological experiments lend support to the clinical observation that the intensity and duration of a psychiatric disorder may adversely alter its long-term course. Rapid aggressive treatment may prevent this from occurring. While pharmacotherapy may reduce the duration and severity of symptoms, it may also have an independent, as yet unknown, effect on neuroplasticity.

scholarly journals Increased neural reactivity to emotional pictures in men with high hair testosterone concentrations

2019 ◽  
Vol 14 (9) ◽  
pp. 1009-1016
Author(s):  
Sanja Klein ◽  
Onno Kruse ◽  
Isabell Tapia León ◽  
Tobias Stalder ◽  
Rudolf Stark ◽  
...  
Keyword(s):  
Emotional Reactivity ◽  
Neural Activation ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Testosterone Levels ◽  
Passive Viewing ◽  
Emotional Pictures ◽  
Neural Reactivity ◽  
The Brain

Abstract Testosterone has been linked to alterations in the activity of emotion neurocircuitry including amygdala, orbitofrontal cortex (OFC) and insula and diminished functional amygdala/prefrontal coupling. Such associations have only ever been studied using acute measures of testosterone, thus little is known about respective relationships with long-term testosterone secretion. Here, we examine associations between hair testosterone concentration (HTC), an index of long-term cumulative testosterone levels and neural reactivity during an emotional passive viewing task using functional magnetic resonance imaging (fMRI). Forty-six men viewed negative, positive and neutral pictures in the MRI. HTCs were assessed from 2 cm hair segments. The emotional paradigm elicited neural activation in the amygdala, insula and OFC. HTCs were associated with increased reactivity to negative pictures in the insula and increased reactivity to positive pictures in the OFC. We show an association of long-term testosterone levels with increased emotional reactivity in the brain. These results suggest a heightened emotional vigilance in individuals with high trait testosterone levels.

Enhanced fever following castration: possible involvement of brain arginine vasopressin

1988 ◽  
Vol 254 (3) ◽  
pp. R513-R517 ◽  
Author(s):  
Q. J. Pittman ◽  
T. J. Malkinson ◽  
N. W. Kasting ◽  
W. L. Veale
Keyword(s):  
Arginine Vasopressin ◽  
Wistar Rats ◽  
Prostaglandin E1 ◽  
Interleukin 1 ◽  
Lateral Septum ◽  
Male Wistar Rats ◽  
Thermal Indexes ◽  
The Brain ◽  
Lateral Cerebral Ventricle

Arginine vasopressin (AVP) is thought to act as an antipyretic in the ventral-septal area (VSA) of the brain. As AVP content of this area has been shown to be virtually eliminated following long-term castration, we have tested the hypothesis that castrated rats would display enhanced fevers. Four months after castration (or sham castration), male Wistar rats were given prostaglandin E1 (200 ng), purified interleukin 1 (25 U), or saline (5 microliters) into a lateral cerebral ventricle. Castrated rats displayed fevers of longer duration, reflected as significantly enhanced thermal indexes, than did age-matched sham-operated controls. Castrated rats also were less able to defend their body temperatures to ambient heat stress but not to ambient cold. AVP content of VSA and lateral septum, but not of hippocampus, of castrated rats was significantly reduced; oxytocin content of the three areas was unchanged following castration. These data support earlier studies concerning effects of castration on septal AVP content and are consistent with the possibility that AVP is an antipyretic in the VSA of the rat.

scholarly journals Psychiatric Disorders after Transurethral Resection of the Prostate

1998 ◽  
Vol 91 (1) ◽  
pp. 13-15 ◽  
Author(s):  
Rosemary Lethem ◽  
Gianetta Rands
Keyword(s):  
Psychiatric Disorders ◽  
Transurethral Resection ◽  
Transurethral Prostatectomy ◽  
Long Term Changes ◽  
The Brain

Three men in their 70s had long-term changes in mood and personality dating from immediately after transurethral prostatectomy. Focal abnormalities in the brain were not detected. The possibility of psychiatric as well as cardiovascular sequelae from this operation deserves investigation.

On the unique profile of action of clozapine as assessed with fos-protein induction in rat brain regions

1997 ◽  
Vol 9 (2) ◽  
pp. 55-57 ◽  
Author(s):  
J. Korf ◽  
D. Andries ◽  
J.B. Sebens
Keyword(s):  
Brain Regions ◽  
Cellular Level ◽  
Lateral Septum ◽  
Early Gene ◽  
Binding Assays ◽  
Fos Protein ◽  
Vitro Binding

Clozapine (Leponex®) has been shown to be therapeutically effective in patients resistant to long-term medication with classical antipsychotics. The mode of action of clozapine is not clear, but several cerebral receptors have been implicated, including the dopamine D2, D3 and D4 types, α-adrenergic, serotonin (type 2A) and glutamate (NMDA-type) receptors. Moreover, clozapine has anti-cholinergic and antihistaminergic potencies. Thusfar, receptor profiles are based virtually exclusively on in vitro binding assays. It appeared, that pharmacological and physiological stimuli activate particular gene expression, in vivo, so at cellular level the action of e.g. antipsychotics can now be traced. In this communication we present data on the in vivo profile of clozapine as revealed with Fos-protein expression. The immediate early gene c-fos is, as other members of the class of such genes, rapidly and transiently induced in the brain. The prototypic members of this class all encode nuclear proteins that regulate gene transcription. Recent studies have shown that the antipsychotics haloperidol (Haldol®) and clozapine, when given acutely, induce different patterns of Fos-like immunoreactivity in the forebrain of the rat. The most marked effects of haloperidol were found in the striatum, the nucleus accumbens and the lateral septum.

scholarly journals Catalysts for change: the cellular neurobiology of psychedelics

2021 ◽  
Vol 32 (12) ◽  
pp. 1135-1144
Author(s):  
Matthew I. Banks ◽  
Zarmeen Zahid ◽  
Nathan T. Jones ◽  
Ziyad W. Sultan ◽  
Cody J. Wenthur
Keyword(s):  
Psychiatric Disorders ◽  
Neural Plasticity ◽  
Structural Changes ◽  
Therapeutic Potential ◽  
Behavioral Effects ◽  
Long Term Effects ◽  
Neural Basis ◽  
And Behavior ◽  
The Brain

The resurgence of interest in the therapeutic potential of psychedelics for treating psychiatric disorders has rekindled efforts to elucidate their mechanism of action. In this Perspective, we focus on the ability of psychedelics to promote neural plasticity, postulated to be central to their therapeutic activity. We begin with a brief overview of the history and behavioral effects of the classical psychedelics. We then summarize our current understanding of the cellular and subcellular mechanisms underlying these drugs’ behavioral effects, their effects on neural plasticity, and the roles of stress and inflammation in the acute and long-term effects of psychedelics. The signaling pathways activated by psychedelics couple to numerous potential mechanisms for producing long-term structural changes in the brain, a complexity that has barely begun to be disentangled. This complexity is mirrored by that of the neural mechanisms underlying psychiatric disorders and the transformations of consciousness, mood, and behavior that psychedelics promote in health and disease. Thus, beyond changes in the brain, psychedelics catalyze changes in our understanding of the neural basis of psychiatric disorders, as well as consciousness and human behavior.

scholarly journals Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice

2021 ◽  
Vol 187 ◽  
pp. 108495
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla-Perez ◽  
Jacques Nguyen ◽  
Victoria B. Risbrough ◽  
Michael A. Taffe ◽  
...  
Keyword(s):  
Behavioral Abnormalities ◽  
Adolescent Exposure

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

Metabolic abnormalities in patients with chronic psychiatric disorders receiving long-term psychopharmacological treatment

2005 ◽  
Vol 38 (05) ◽  
Author(s):  
B Reisinger ◽  
E Mueller ◽  
B Kropp-Hartmann ◽  
D Wölflick ◽  
C Zimmerer ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Metabolic Abnormalities ◽  
Psychopharmacological Treatment
Sign in / Sign up

Export Citation Format

Share Document