High dose of dexamethasone protects against EAE-induced motor deficits but impairs learning/memory in C57BL/6 mice.
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ABSTRACT:
SUBMITTER: Dos Santos N
PROVIDER: S-EPMC6491620 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:Anterograde interference emerges when two differing tasks are learned in close temporal proximity, an effect repeatedly attributed to a competition between differing task memories. However, recent development alternatively suggests that initial learning may trigger a refractory period that occludes neuroplasticity and impairs subsequent learning, consequently mediating interference independently of memory competition. Accordingly, this study tested the hypothesis that interference can emerge when the same motor task is being learned twice, that is when competition between memories is prevented. In a first experiment, the inter-session interval (ISI) between two identical motor learning sessions was manipulated to be 2 min, 1 h or 24 h. Results revealed that retention of the second session was impaired as compared to the first one when the ISI was 2 min but not when it was 1 h or 24 h, indicating a time-dependent process. Results from a second experiment replicated those of the first one and revealed that adding a third motor learning session with a 2 min ISI further impaired retention, indicating a dose-dependent process. Results from a third experiment revealed that the retention impairments did not take place when a learning session was preceded by simple rehearsal of the motor task without concurrent learning, thus ruling out fatigue and confirming that retention is impaired specifically when preceded by a learning session. Altogether, the present results suggest that competing memories is not the sole mechanism mediating anterograde interference and introduce the possibility that a time- and dose-dependent refractory period-independent of fatigue-also contributes to its emergence. One possibility is that learning transiently perturbs the homeostasis of learning-related neuronal substrates. Introducing additional learning when homeostasis is still perturbed may not only impair performance improvements, but also memory formation.
| S-EPMC7892403 | biostudies-literature
Project description:Memory deficits significantly decrease an individual's quality of life and are a pervasive comorbidity of epilepsy. Despite the various distinct processes of memory, the majority of epilepsy research has focused on seizures during the encoding phase of memory, therefore the effects of a seizure on other memory processes is relatively unknown. In the present study, we investigated how a single seizure affects memory reactivation in C57BL/6J adult mice using an associative conditioning paradigm. Initially, mice were trained to associate a tone (conditioned stimulus), with the presence of a shock (unconditioned stimulus). Flurothyl was then administered 1 h before, 1 h after, or 6 h before a memory reactivation trial. The learned association was then assessed by presenting a conditioned stimulus in a new context 24 h or 1 wk after memory reactivation. We found that mice receiving a seizure 1 h prior to reactivation exhibited a deficit in memory 24 h later but not 1 wk later. When mice were administered a seizure 6 h before or 1 h after reactivation, there were no differences in memory between seizure and control animals. Altogether, our study indicates that an acute seizure during memory reactivation leads to a temporary deficit in associative memory in adult mice. These findings suggest that the cognitive impact of a seizure may depend on the timing of the seizure relative to the memory process that is active.
| S-EPMC7433655 | biostudies-literature
Project description:BackgroundFormation and maintenance of appropriate neural networks require tight regulation of neural stem cell proliferation, differentiation, and neurogenesis. microRNAs (miRNAs) play an important role in brain development and plasticity, and dysregulated miRNA profiles have been linked to neurodevelopmental disorders including autism, schizophrenia, or intellectual disability. Yet, the functional role of miRNAs in neural development and postnatal brain functions remains unclear.MethodsUsing a combination of cell biology techniques as well as behavioral studies and brain imaging, we characterize mouse models with either constitutive inactivation or selectively hippocampal knockdown of the neurodevelopmental disease-associated gene Mir146a, the most commonly deregulated miRNA in developmental brain disorders (DBD).ResultsWe first show that during development, loss of miR-146a impairs the differentiation of radial glial cells, neurogenesis process, and neurite extension. In the mouse adult brain, loss of miR-146a correlates with an increased hippocampal asymmetry coupled with defects in spatial learning and memory performances. Moreover, selective hippocampal downregulation of miR-146a in adult mice causes severe hippocampal-dependent memory impairments indicating for the first time a role for this miRNA in postnatal brain functions.ConclusionOur results show that miR-146a expression is critical for correct differentiation of neural stem cell during brain development and provide for the first time a strong argument for a postnatal role of miR-146a in regulating hippocampal-dependent memory. Furthermore, the demonstration that the Mir146a-/- mouse recapitulates several aspects reported in DBD patients, including impaired neurogenesis, abnormal brain anatomy, and working and spatial memories deficits, provides convincing evidence that the dysregulation of miR146a contributes to the pathogenesis of DBDs.
| S-EPMC7106595 | biostudies-literature
Project description:The Supplementary Motor Area (SMA)-located in the superior and medial aspects of the superior frontal gyrus-is a preferential site of certain brain tumors and arteriovenous malformations, which often provoke the so-called SMA syndrome. The bulk of the literature studying this syndrome has focused on two of its most apparent symptoms: contralateral motor and speech deficits. Surprisingly, little attention has been given to working memory (WM) even though neuroimaging studies have implicated the SMA in this cognitive process. Given its relevance for higher-order functions, our main goal was to examine whether WM is compromised in SMA lesions. We also asked whether WM deficits might be reducible to processing speed (PS) difficulties. Given the connectivity of the SMA with prefrontal regions related to executive control (EC), as a secondary goal we examined whether SMA lesions also hampered EC. To this end, we tested 12 patients with lesions involving the left (i.e., the dominant) SMA. We also tested 12 healthy controls matched with patients for socio-demographic variables. To ensure that the results of this study can be easily transferred and implemented in clinical practice, we used widely-known clinical neuropsychological tests: WM and PS were measured with their respective Wechsler Adult Intelligence Scale indexes, and EC was tested with phonemic and semantic verbal fluency tasks. Non-parametric statistical methods revealed that patients showed deficits in the executive component of WM: they were able to sustain information temporarily but not to mentally manipulate this information. Such WM deficits were not subject to patients' marginal PS impairment. Patients also showed reduced phonemic fluency, which disappeared after controlling for the influence of WM. This observation suggests that SMA damage does not seem to affect cognitive processes engaged by verbal fluency other than WM. In conclusion, WM impairment needs to be considered as part of the SMA syndrome. These findings represent the first evidence about the cognitive consequences (other than language) of damage to the SMA. Further research is needed to establish a more specific profile of WM impairment in SMA patients and determine the consequences of SMA damage for other cognitive functions.
| S-EPMC5974158 | biostudies-literature
Project description:Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.
| S-EPMC4105541 | biostudies-literature
Project description:Rapid learning can be critical to ensure elite performance in a changing world or to recover basic movement after neural injuries. Recently it was shown that the variability of follow-through movements affects the rate of motor memory formation. Here we investigate if lead-in movement has a similar effect on learning rate. We hypothesized that both modality and variability of lead-in movement would play critical roles, with simulations suggesting that only changes in active lead-in variability would exhibit slower learning. We tested this experimentally using a two-movement paradigm, with either visual or active initial lead-in movements preceeding a second movement performed in a force field. As predicted, increasing active lead-in variability reduced the rate of motor adaptation, whereas changes in visual lead-in variability had little effect. This demonstrates that distinct neural tuning activity is induced by different lead-in modalities, subsequently influencing the access to, and switching between, distinct motor memories.
| S-EPMC5552870 | biostudies-other
Project description:Iron is involved in various physiological processes of the human body to maintain normal functions. Abnormal iron accumulation in brain has been reported as a pathogenesis of several neurodegenerative disorders and cognitive impairments. Hemojuvelin (HVJ) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis. Although iron accumulation in brain has been related to neurodegenerative diseases, it remains unknown the effect of mutation of HVJ gene on cognitive performance. In our studies, HJV(-/-) mice showed deficits in novel object recognition and Morris water maze tests. Furthermore, the expression ration of apoptotic marker Bax and anti-apoptotic marker Bcl-2 in the hippocampus and prefrontal cortex showed higher levels in HJV(-/-) mice. Our results suggested that deletion of HJV gene could increase apoptosis in brain which might contribute to learning and memory deficits in mutant mice. These results indicated that HJV(-/-) mice would be a useful model to study cognitive impairment induced by iron overload in brain.
| S-EPMC4638289 | biostudies-literature
Project description:Secretin (SCT) was first considered to be a gut hormone regulating gastrointestinal functions when discovered. Recently, however, central actions of SCT have drawn intense research interest and are supported by the broad distribution of SCT in specific neuronal populations and by in vivo physiological studies regarding its role in water homeostasis and food intake. The direct action of SCT on a central neuron was first discovered in cerebellar Purkinje cells in which SCT from cerebellar Purkinje cells was found to potentiate GABAergic inhibitory transmission from presynaptic basket cells. Because Purkinje neurons have a major role in motor coordination and learning functions, we hypothesize a behavioral modulatory function for SCT. In this study, we successfully generated a mouse model in which the SCT gene was deleted specifically in Purkinje cells. This mouse line was tested together with SCT knockout and SCT receptor knockout mice in a full battery of behavioral tasks. We found that the knockout of SCT in Purkinje neurons did not affect general motor ability or the anxiety level in open field tests. However, knockout mice did exhibit impairments in neuromuscular strength, motor coordination, and motor learning abilities, as shown by wire hanging, vertical climbing, and rotarod tests. In addition, SCT knockout in Purkinje cells possibly led to the delayed development of motor neurons, as supported by the later occurrence of key neural reflexes. In summary, our data suggest a role in motor coordination and motor learning for SCT expressed in cerebellar Purkinje cells.
| S-EPMC3988549 | biostudies-other
Project description:Subclinical hyperthyroidism, a disease characterized by decreased thyroid-stimulating hormone (TSH) and normal concentration of thyroid hormone, is associated with an elevated risk for cognitive impairment. TSH is the major endogenous ligand of TSH receptor (TSHR) and its role dependent on the process of signal transduction of TSHR. It has not, however, been established whether TSHR signaling are involved in the regulation of cognition. In the current study, Tshr deletion leads to significantly compromised performance in hippocampus-dependent tasks, along with reduced dendritic spine density and excitatory synaptic density as well as altered synaptic structure in CA1 subfield of the hippocampus. Furthermore, the synapse-related gene expression was altered in the hippocampus of Tshr-/- mice. These findings suggest the ablation of TSHR signaling impairs spatial learning and memory, which reveals a fresh role of TSHR signaling in brain.
2022-02-28 | GSE145958 | GEO
Project description:Parkinson's disease, which affects the basal ganglia, is known to lead to various impairments of motor control. Since the basal ganglia have also been shown to be involved in learning processes, motor learning has frequently been investigated in this group of patients. However, results are still inconsistent, mainly due to skill levels and time scales of testing. To bridge across the time scale problem, the present study examined de novo skill learning over a long series of practice sessions that comprised early and late learning stages as well as retention. 19 non-demented, medicated, mild to moderate patients with Parkinson's disease and 19 healthy age and gender matched participants practiced a novel throwing task over five days in a virtual environment where timing of release was a critical element. Six patients and seven control participants came to an additional long-term retention testing after seven to nine months. Changes in task performance were analyzed by a method that differentiates between three components of motor learning prominent in different stages of learning: Tolerance, Noise and Covariation. In addition, kinematic analysis related the influence of skill levels as affected by the specific motor control deficits in Parkinson patients to the process of learning. As a result, patients showed similar learning in early and late stages compared to the control subjects. Differences occurred in short-term retention tests; patients' performance constantly decreased after breaks arising from poorer release timing. However, patients were able to overcome the initial timing problems within the course of each practice session and could further improve their throwing performance. Thus, results demonstrate the intact ability to learn a novel motor skill in non-demented, medicated patients with Parkinson's disease and indicate confounding effects of motor control deficits on retention performance.
| S-EPMC3132742 | biostudies-literature