Developing Novel Experimental Models of m-TORopathic Epilepsy and Related Neuropathologies: Translational Insights from Zebrafish.

The mammalian target of rapamycin (mTOR) is an important molecular regulator of cell growth and proliferation. Brain mTOR activity plays a crucial role in synaptic plasticity, cell development, migration and proliferation, as well as memory storage, protein synthesis, autophagy, ion channel expression and axonal regeneration. Aberrant mTOR signaling causes a diverse group of neurological disorders, termed 'mTORopathies'. Typically arising from mutations within the mTOR signaling pathway, these disorders are characterized by cortical malformations and other neuromorphological abnormalities that usually co-occur with severe, often treatment-resistant, epilepsy. Here, we discuss recent advances and current challenges in developing experimental models of mTOR-dependent epilepsy and other related mTORopathies, including using zebrafish models for studying these disorders, as well as outline future directions of research in this field.

Alpha2-Adrenoblockers Regulate Development of Oxidative Stress and Cognitive Behaviour of Rats under Chronic Acoustic Stress Conditions.

Noise is a wide-spread stress factor in modern life produced by urbanization, traffic, and an industrialized environment. Noise stress causes dysfunction and neurotransmission impairment in the central nervous system, as well as changes in hormone levels. In this study, we have examined the level of α-Tocopherol (α-T) and malondialdehyde (MDA) in plasma and the erythrocytes' membrane (EM), as well as the behavioral characteristics of a noise-induced stress model in rats. In addition, the modulating effect of α2-adrenoblockers, beditin, and mesedin on the aforementioned parameters has been investigated. For these purposes, albino male rats were divided into four groups: (1) untreated; (2) noise-exposed, (3) noise-exposed and beditin-treated (2 mg/kg, i.p.), and (4) noise-exposed and mesedin-treated (10 mg/kg, i.p.) animals. Noise-exposed groups were treated with 91dBA noise on 60 days with a daily duration of 8 h. Increased MDA and decreased α-T levels in plasma and EM were observed upon chronic high-level noise exposure. Locomotor and behavioral activity assessed with a Y-maze revealed disorientation and increased anxiety under chronic noise exposure. Prominently, α2-adrenoblockers alleviated both behavioral deficits and oxidative stress, providing evidence for the involvement of α2-adrenoceptor in the pathophysiology of noise-induced stress.

Adrenergic alpha-2 receptor antagonists cease augmented oxidation of plasma proteins and anxiety of rats caused by chronic noise exposure.

BACKGROUND: Noise is one of the environmental factors, which is considered as a powerful stressor for the organism. Generally, the acoustic stress affects the behavior and physiological state of humans and animals. AIMS: The goal of this study is to investigate the relationship between chronic noise exposure and the effects of adrenergic alpha-2 receptor antagonists, beditin and mesedin, on the anxiety and oxidation of plasma proteins and fibrinogen in rats. METHODS: The experiments were carried out on non-linear albino male rats, divided into four groups (six animals in each): 1. Healthy controls 2. Exposed to noise of a level 91 dB(A), eight hours daily, during 7, 30 and 60 days; 3. Injected with 2 mg/kg of beditin (2-(2-amino-4-thiazolyl)-1,4-benzodioxane hydrochloride)); 4. Injected with 10 mg/kg mesedin (2-(2-methyl-amino-thiozolyl)-1,4-benzodioxane hydrochloride). For evaluating the cognitive impairment, the Any-maze test was applied. The level of carbonylation of proteins was assessed by reaction with 2,4-dinitrophenylhydrazine, spectrophotometrically. RESULTS: Chronic noise decreased locomotor activity and increased anxiety and oxidation of plasma protein and fibrinogen. Intensity of these changes were dependent on the duration of noise exposure. CONCLUSION: The Alpha 2 adrenoblockers alleviate oxidative modification of plasma proteins and reduce the cognitive impairment caused by chronic exposure to noise.

Advances in understanding the pathophysiology of autism spectrum disorders.

Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental disorders with typical triad of symptoms: impaired social interaction, language and communication abnormalities and stereotypical behavior. Despite extensive research, the etiology and pathogenesis of ASD remain largely unclear. The lack of solid knowledge on the mechanisms of these disorders decreases the opportunities for pathogenetic treatment of autism. Various theories where proposed in order to explain the pathophysiology underlying ASD. Despite the fact that none of them is able to completely explain the impairments in the nervous system of ASD patients, these hypotheses were instrumental in highlighting the most important mechanisms in the development of this complex disorder. Some new theories are based on neurovisualization studies, others on the data from genomic studies, which become increasingly available worldwide. As the research in this field is largely dependent on the animal models, there is an ongoing discussion and search for the most appropriate one adequately reproducing the pathology. Here we provide an overview of current theories of the origin and development of ASD discussed in the context of existing and proposed rodent models of ASD.