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Variants in the SPATA5gene were recently described in a cohort of patients with global developmental delay, sensorineural hearing loss, seizures, cortical visual impairment and microcephaly. SPATA5 protein localizes predominantly in the mitochondria and is proposed to be involved in mitochondrial function and brain developmental processes. However no functional studies have been performed. This study describes five patients with psychomotor developmental delay, microcephaly, epilepsy and hearing impairment, who were thought clinically to have a mitochondrial disease with subsequent whole-exome sequencing analysis detecting compound heterozygous variants in the SPATA5gene. A summary of clinical data of all the SPATA5 patients reported in the literature confirms the characteristic phenotype. To assess SPATA5’s role in mitochondrial dynamics, functional studies were performed on rat cortical neurons. SPATA5-deficient neurons had a significant imbalance in the mitochondrial fusion-fission rate, impaired energy production and short axons. In conclusion, SPATA5 protein has an important role in mitochondrial dynamics and axonal growth. Biallelic variants in the SPATA5gene can affect mitochondria in cortical neurons and should be considered in patients with a neurodegenerative disorder and/or with clinical presentation resembling a mitochondrial disorder.

Many real-life optimization problems are of the multiobjective type and highdimensional. Possibilities for solving large scale optimization problems on a computer network or multiprocessor computer using a multi-level approach are studied. The paper treats numerical methods in which procedural and rounding errors are unavoidable, for example, those arising in mathematical modelling and simulation. For the solution of involving decomposition-coordination problems some rapidly convergent interative methods are developed based on the classical cubically convergent method of tangent hyperbolas (Chebyshev-Halley method) and the method of tangent parabolas (Euler-Chebyshev method). A family of iterative methods having the convergence order equal to four is also considered. Convergence properties and computational aspects of the methods under consideration are examined. The problems of their global implementation and polyalgorithmic strategy are discussed as well.

Cocaine- and amphetamine-regulated transcript (CART) is a novel neuropeptide with neurotransmitter-like effects. In the present study we examined the influence of CART peptide fragment, CART62–76, on the levels of catecholamines (dopamine and norepinephrine), serotonin and their metabolites in five regions of the rat brain. CART62–76was administered at 0.5 or 5.0μg dose intracerebroventricularly. A high-pressure liquid chromatograph coupled to electrochemical array detector was used to analyse the tissue homogenates. In the frontal cortex, CART62–76increased the levels of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin (5-HT). In the striatum, CART62–76decreased the levels of noradrenaline and 5-HT. In the hypothalamus, CART62–76increased thelevels of 5-HIAA. CART62–76had no significant effect in the hippocampus and cerebellum. Our data suggest that CART62–76peptide has no major effect on dopaminergic pathways, but it modulates the activity of striatal noradrenergic and corticostriatal and hypothalamic serotoninergic system in the rat brain. These regionally selective neurochemical changes may explain the effects of CART peptides on appetitive, emotional and locomotor behaviour.

We have studied the effect of acute trazodone (3–20 mg kg−1) and quipazine (1–3 mg kg−1) treatment on the apomorphine-induced (1 mg kg−1, once daily over 2 weeks) aggressive behaviour in male Wistar rats. All doses of trazodone and quipazine tested attenuated the aggressiveness as evidenced by the abolished intensity of aggressive behaviour and increased time of latency before the first attack. The acute trazodone (3–10 mg kg−1) or quipazine (1–3 mg kg−1) treatment had no or only a minor effect on rat behaviour in the elevated plus-maze, open field, and forced swimming test. Concomitant apomorphine (1 mg kg−1) plus trazodone (3 mg kg−1), but not apomorphine (1 mg kg−1) plus quipazine (1 mg kg−1), treatment slowed the development of aggressive behaviour. Repeated apomorphine treatment moderately reduced the dopamine post mortemand increased the DOPAC and HVA contents in striatum. Other monoamines or their metabolites were unchanged. Neither trazodone and quipazine treatment nor forced swimming stress induced any changes in the monoamine contents. In conclusion, our results indicate that acute trazodone and quipazine treatment attenuates the apomorphine-induced aggressive behaviour in male rats, but this phenomenon cannot be implicated in the changes in emotional and motivational behaviour, or in changes of monoamine content post mortem.

The aim of this study was to investigate the role of serotoninergic neurotransmission and the effect of acute para-chlorophenylalanine (350 mg/kg, intraperitoneally) treatment on apomorphine-induced aggressive behaviour in adult male Wistar rats. In addition, [3H]ketanserin binding and monoamine content were studied. Repeated administration of apomorphine (1.0 mg/kg, subcutaneously, once daily for two weeks) gradually induced aggressive behaviour. Acute p-chlorophenylalanine treatment down-regulated the [3H]ketanserin binding and reduced over 90 per cent the content of serotonin and 5-hydroxyindolacetic acid. In a half of the p-chlorophenylalanine-treated animals, the aggressive behaviour was suppressed, while there was no difference in [3H]ketanserin binding or monoamine content between the p-chlorophenylalanine treated aggressive and non-aggressive animals. In conclusion, the acute p-chlorophenylalanine treatment attenuates the aggressiveness only in half of the animals, while the latter phenomenon is independent on the CNS monoamine content or [3H]ketanserin binding.