Neurophysiological maturation in adolescence - vulnerability and counteracting addiction to alcohol.

The results of contemporary studies confirm the formation of two neural networks in the brain during the period of adolescence. The first is defined as emotional, located in the limbic system, develops earlier, quicker, and more intensively than the second one in the prefrontal cortex, called the judgement network, which fulfils the role of control and inhibition of emotional reactions. The domination of the emotional network in adolescence is manifested by hyperactivity of the limbic system, accompanied by intensified undertaking of courageous, reckless, risky, or even sometimes dangerous actions, so very characteristic in the maturation. The aim of the article is to present the state of the art in the field of latest achievements in experimental neurophysiology related to the maturation of the structural end functional processes in adolescents, and to alcohol vulnerability. Alcohol effect initiation starts in early adolescence, and therefore is connected with alcohol abuse and addiction in adulthood, which confirms the necessity for provision of an early prophylactic protection for juveniles, even before entering the phase of early adolescence. Some electrophysiological characteristics, such as low P3 amplitude of the Event-Related Potential (ERP) and Event-Related Oscillations (EROs), are manifested by their high risk offspring, and are considered to be biological markers (endophenotypes) of a predisposition to develop alcohol use disorders. Electroencephalographic oscillations induced within the range of the theta and delta waves (Event-Related Oscillation- ERO), considered as endophenotypes and markers of increased vulnerability for addiction, present three groups of genes and three types of neurotransmitters, with gamma aminobutyric acid, acetylcholine and glutamate as neurotransmitters in the central nervous system. A new research approach consisting in the application of electroencephalographic methods and techniques in developmental and genetic studies of the conditioning of varied vulnerability, and especially increased preferences for alcohol tasting and abuse in adolescence, provide unique possibilities for comprehensive and deepened studies which may contribute to the prevention of alcohol addiction, the genesis of which, to a great extent, is related with the effect of causative environmental and genetic factors during adolescent development.

Event-related potentials (ERP) and SGIP1 gene polymorphisms in alcoholics: relation to family history of alcoholism and drug usage.

OBJECTIVE: The electrophysiological characteristics may serve as valuable biomarkers for the genetic vulnerability underlying alcoholism. The purpose of this study was to evaluate the potential associations between single nucleotide polymorphisms (SNPs) located in the SGIP1 gene and the theta ERP quantitative traits. METHOD: The theta band (4-7 Hz) visual ERP occurring in the P300 response in the resting EEG were examined to explore the electrophysiological effects of alcohol on the brain in five regions: frontal, central, parietal, temporal and occipital in patients with alcohol addiction. In addition, we tested the potential associations between single nucleotide polymorphisms (SNPs) located in the SGIP1 gene and ERP quantitative traits. RESULTS: We found that the amplitude of the auditory P300 response differed considerably among groups of alcoholics in the frontal, central and temporal areas of the brain and it was lower in the studied brain regions in alcoholics in comparison to non-alcoholics. However, among subjects in the young adult group (GR-1) there was no statistical difference in amplitude of P300 response with control subjects in all studied brain regions in comparison with non-alcoholics. Moreover, we revealed that SNP rs10889635 had a significant effect on P300 amplitude in the central and temporal regions. The reduced P300 amplitude was in AA carriers in comparison to both carriers of GG and GA alleles. CONCLUSION: The present study demonstrated a possible association of target P300 evoked theta and of alcohol dependence with SNPs from the gene SGIP1 in the region of rs10889635, but further studies are required.

Epigenetic regulation in drug addiction.

The interaction between environmental signals and genes has now taken on a clear molecular form as demonstrated by stable changes in chromatin structure. These changes occur through activation or repression of specific gene programmes by a combination of chromatin remodelling, activation and enzymatic modification of DNA and histones as well as nucleosomal subunit exchange. Recent research investigating the molecular mechanisms controlling drug-induced transcriptional, behavioural and synaptic activity has shown a direct role for chromatin remodelling--termed as epigenetic regulation--of neuronal gene programmes and subsequent addictive behaviour arising from it. Recent data suggest that repeated exposure to certain drugs promotes changes in levels of histone acetylation, phosphorylation and methylation, together with alterations in DNA methylation levels in the neurons of the brain reward centre, localised in the Nucleus Accumbens (NAc) region of the limbic system. The combination of acetylating, phosphorylating and methylating H3 and H4 histone tails alter chromatin compaction thereby promoting altered levels of cellular gene expression. Histone modifications, which weaken histone interaction with DNA or that promote recruitment of transcriptional activating complexes, correlate with permissive gene expression. Histone deacetylation, (which strengthen histone: DNA contacts), or histone methylation, (which recruits repressive complexes to chromatin), promote a state of transcriptional repression. Using animal models, acute cocaine treatment increases H4 acetylation at acutely regulated gene promoters, whereas H3 acetylation appears to predominate at chronically induced promoters. Chronic cocaine and alcohol treatment activate and repress many genes such as FosB, Cdk5, and Bdnf, where their dysregulation, at the chromatin level, contribute to the development and maintenance of addiction. Following drug exposure, it is still unknown, howver, how long these changes in chromatin structure persist in affecting neuronal function, but some do so for life.

Effects of combined maternal administration with alpha-ketoglutarate (AKG) and ß-hydroxy-ß-methylbutyrate (HMB) on prenatal programming of skeletal properties in the offspring.

BACKGROUND: Nutritional manipulations during fetal growth may induce long-term metabolic effects in postnatal life. The aim of the study was to test whether combined treatment of pregnant sows with alpha-ketoglutarate and ß-hydroxy-ß-methylbutyrate induces additive long-term effects on skeletal system properties in the offspring. METHODS: The study was performed on 290 pigs obtained from 24 sows divided into 4 equal groups and subjected to experimental treatment during two weeks before delivery. The first group consisted of control sows, while the second group received alpha-ketoglutarate. The third group was treated with ß-hydroxy-ß-methylbutyrate and the fourth group underwent combined administration of alpha-ketoglutarate and ß-hydroxy-ß-methylbutyrate. Piglets obtained from sows were reared until slaughter age to perform morphometric, densitometric and mechanical analyses of femur. Serum evaluations of growth hormone, insulin-like growth factor-1, bone-specific alkaline phosphatase and osteocalcin were performed in newborns and 90-day old piglets; additionally, plasma amino acid concentration was measured in newborns. RESULTS: Maternal treatment with alpha-ketoglutarate and ß-hydroxy-ß-methylbutyrate significantly reduced fattening time and increased birth body weight, daily body weight gain, bone weight, volumetric bone mineral density, geometrical parameters and mechanical endurance of femur. These effects were associated with increased serum concentrations of growth hormone, insulin-like growth factor-1, bone-specific alkaline phosphatase and osteocalcin. Furthermore, alpha-ketoglutarate and ß-hydroxy-ß-methylbutyrate administered solely or in combination significantly increased plasma level of 19 amino acids. CONCLUSIONS: Hormonal and amino acid evaluations in pigs indicate additive effects of AKG and HMB on systemic growth and development; however, determination of bone properties has not shown such phenomenon.

Aged garlic extract and allicin improve performance and gastrointestinal tract development of piglets reared in artificial sow.

This study was performed to investigate whether postnatal administration with aged garlic extract (AGE) and allicin influences performance and systemic development of piglets exposed to early weaning. Twenty-four male piglets were weaned from sows at the age of two days of life, divided into 4 weight-matched groups and kept under conditions of artificial sow for 6 days. The first group consisted of control animals, while piglets that were given AGE daily per os at the dosages of 1 ml and 2 ml/kg body weight, respectively belonged to the second and third group. The fourth group consisted of piglets administered orally with allicin at the dosage of 1.0 mg/kg body weight/day. At the age of 8 days of life all animals were sacrificed. Next to body weight gain and morphological properties of the gastrointestinal tract, the haematological examination was performed, and activity of lysozyme and ceruloplasmin as well as level of gamma-globulins were determined. The obtained results showed that AGE and allicin improved final body weight, morphological properties of intestine villi and non-specific defence mechanisms of pigs. All these results indicate that AGE and allicin induced beneficial effects on health status, performance and systemic development of piglets.

The influence of alpha-ketoglutarate (AKG) on mineralisation, mechanical and structural properties of ulna in turkey under conditions of osteotomy and denervation.

Background. Mechanical endurance of bones to acting forces is a result of geometrical properties, mineralisation and quality of the material they are built. Bone mineral density decrease influences lower bone mechanical endurance and its higher susceptibility on fractures. Among many factors that condition proper growth, development and repair processes of skeletal system, nervous system plays very important role in processes of bone metabolism regulation and its homeostasis maintenance. Bone fractures occurrence as a result of osteopenia and its fractures connected with peripheral nervous system injury require investigations of new and effective treatments that would guarantee correct repair processes of bone tissue and its physiological function maintenance. Material and methods. All investigation was performed on 16 turkeys divided into two groups. Right ulnae were subjected to denervation, osteotomy and osteosynthesis. The first group of turkeys served as control, the second group were administered alpha-ketoglutarate (AKG) directly to crop at the dosage of 0.4g/kg b.w./day by 14 weeks, starting on the next day after surgery. After finishing breeding part of experiment, the influence of AKG on mineralisation, structural and mechanical properties of denervated and osteotomied ulna was investigated. Results. Performed investigations on ulna after its osteotomy and denervation elucidated different callus formation in turkeys belong to control group and receiving AKG. The positive influence of alpha-ketoglutarate administration on morphology, mineralisation and mechanical properties of experimentally osteotomied and denervated ulna was stated.Conclusions. Obtained results prove anabolic effect of alpha-ketoglutarate on bone tissue, after its administration via digestive tract. Considering increased mineralisation, higher volumetric cortical bone density and increased trabecular bone density, AKG can be utilised as a factor in prevention of osteopenia and osteoporosis. Achieved results indicate possibility of existence connection by AKG between digestive system and skeletal system.