ubtor Mutation Causes Motor Hyperactivity by Activating mTOR Signaling in Zebrafish

Mechanistic target of rapamycin (mTOR) signaling governs important physiological and pathological processes key to cellular life. Loss of mTOR negative regulators and subsequent over-activation of mTOR signaling are major causes underlying epileptic encephalopathy. Our previous studies showed that UBTOR/KIAA1024/MINAR1 acts as a negative regulator of mTOR signaling, but whether UBTOR plays a role in neurological diseases remains largely unknown. We therefore examined a zebrafish model and found that ubtor disruption caused increased spontaneous embryonic movement and neuronal activity in spinal interneurons, as well as the expected hyperactivation of mTOR signaling in early zebrafish embryos. In addition, mutant ubtor larvae showed increased sensitivity to the convulsant pentylenetetrazol, and both the motor activity and the neuronal activity were up-regulated. These phenotypic abnormalities in zebrafish embryos and larvae were rescued by treatment with the mTORC1 inhibitor rapamycin. Taken together, our findings show that ubtor regulates motor hyperactivity and epilepsy-like behaviors by elevating neuronal activity and activating mTOR signaling.

Khat and neurobehavioral functions: A systematic review

Background Khat is a plant that is used for its amphetamine-like stimulant properties. However, although khat is very popular in Eastern Africa, Arabian Peninsula, and the Middle East, there is still a lack of studies researching the possible neurobehavioral impairment derived from khat use. Methods A systematic review was conducted to identify studies that assessed the effects of khat use on neurobehavioral functions. MedLine, Scopus, Cochrane, Web of Science and Open Grey literature were searched for relevant publications from inception to December 2020. Search terms included (a) khat and (b) several cognitive domains. References from relevant publications and grey literature were also reviewed to identify additional citations for inclusion. Results A total of 142 articles were reviewed, 14 of which met the inclusion criteria (nine human and five rodent studies). Available human studies suggest that long term khat use is associated with significant deficits in several cognitive domains, including learning, motor speed/coordination, set-shifting/response inhibition functions, cognitive flexibility, short term/working memory, and conflict resolution. In addition, rodent studies indicated daily administration of khat extract resulted in dose-related impairments in behavior such as motor hyperactivity and decreased cognition, mainly learning and memory. Conclusions The findings presented in this review indicates that long-term khat use may be contributing to an impairment of neurobehavioral functions. However, gaps in literature were detected that future studies could potentially address to better understand the health consequences of khat use.

A COMPARATIVE STUDY OF PHENOMENOLOGY BETWEEN EARLY ONSET AND LATE ONSET PSYCHOSIS

Introduction: Phenomenology is the study of subjective experience. Psychiatric diagnoses are based on cross-sectional psychopathological features, for example, the presence of rst-rank symptoms in the case of schizophrenia. Phenomenological investigation focuses on the form of experience, i.e. the way in which the content is experienced, while the content itself is of secondary importance. This study was conducted to investigate the subtle differences between early-onset group (onset before 18 years of age) and late onset (onset after age of 40 years). Aim And Objectives: To study the socio-demographic prole and phenomenology of early onset psychosis and late onset psychosis compare them based on the variables studied. It is a cross sectional observational Materials And Methods: study carried out in the Department of Psychiatry, Gauhati Medical College and Hospital during the period of June 2018- May 2019. A semi structured, self designed proforma has been used to collect the socio-demographic data and personal details of the patients and their treatment history. The ICD-10 Classication of Mental and Behavioural Disorders, WHO, 1992, Brief Psychiatric Rating Scale (BPRS) Version 4.0, Modied Kuppuswamy Socio-economic status scale were used along with. All the data that was derived from the study were analyzed by using the software IBM SPSS 21.0. Observations And Results: Mean age of presentation in early onset psychosis is 19.22 years with Standard Deviation ±5.69. Mean age of presentation in early onset psychosis is 54.5 years with Standard Deviation ±11.9. Signicantly higher ratio of male was noted in early onset group and higher ratio of female was noted in that of the late onset group. Somatic concern, anxiety, depression and suspiciousness was signicantly more in late onset psychosis. In comparison to the group of late onset psychosis, self-neglect, blunted affect, emotional withdrawn, motor retardation, motor hyperactivity, mannerisms and posturing were signicantly more in early-onset psychosis. Major distinction was noted in the Conclusion: distribution of delusional disorders and acute and transient psychotic disorders. Age of onset was skewed to late adolescence with more number of male patients. Late onset psychosis group had more uneducated patients with considerable proportion of adults left unmarried in the late onset group. Late onset psychosis group shows predominance of somatic concern, anxiety, depression and suspiciousness in contrast to early onset psychosis group which shows predominance of motor hyperactivity, self-neglect, blunted affect, motor retardation, mannerisms and posturing

Substantia nigra pars reticulata-mediated sleep and motor activity regulation

Study Objectives The substantia nigra pars reticulata (SNR) is a major output nucleus of the basal ganglia. Animal studies have shown that lesions of the SNR cause hyposomnia and motor hyperactivity, indicating that the SNR may play a role in the control of sleep and motor activity. Methods Eight 8- to 10-week-old adult male Sprague-Dawley rats were used. After 3 days of baseline polysomnographic recording, dialysates were collected from the lateral SNR across natural sleep–wake states. Muscimol and bicuculline were microinfused into the lateral SNR. Results We found that GABA release in the lateral SNR is negatively correlated with slow wave sleep (SWS; R = −0.266, p < 0.01, n = 240) and positively correlated with waking (R = 0.265, p < 0.01, n = 240) in rats. Microinfusion of muscimol into the lateral SNR decreased sleep time and sleep quality, as well as eliciting motor hyperactivity in wake and increased periodic leg movement in SWS, while bicuculline infused into the lateral SNR increased sleep and decreased motor activity in SWS in rats. Muscimol infusion skewed the distribution of inter-movement intervals, with most between 10 and 20 s, while a flat distribution of intervals between 10 and 90 s was seen in baseline conditions. Conclusions Activation of the lateral SNR is important for inducing sleep and inhibiting motor activity prior to and during sleep, and thus to the maintenance of sleep. Abnormal function of the lateral SNR may cause hyposomnia and motor hyperactivity in quiet wake and in sleep.