More than Addiction—The Nucleus Accumbens Contribution to Development of Mental Disorders and Neurodegenerative Diseases

Stress and negative emotions evoked by social relationships and working conditions, frequently accompanied by the consumption of addictive substances, and metabolic and/or genetic predispositions, negatively affect brain function. One of the affected structures is nucleus accumbens (NAc). Although its function is commonly known to be associated with brain reward responses and addiction, a growing body of evidence also suggests its role in some mental disorders, such as depression and schizophrenia, as well as neurodegenerative diseases, such as Alzheimer’s, Huntington’s, and Parkinson’s. This may result from disintegration of the extensive connections based on numerous neurotransmitter systems, as well as impairment of some neuroplasticity mechanisms in the NAc. The consequences of NAc lesions are both morphological and functional. They include changes in the NAc’s volume, cell number, modifications of the neuronal dendritic tree and dendritic spines, and changes in the number of synapses. Alterations in the synaptic plasticity affect the efficiency of synaptic transmission. Modification of the number and structure of the receptors affects signaling pathways, the content of neuromodulators (e.g., BDNF) and transcription factors (e.g., pCREB, DeltaFosB, NFκB), and gene expression. Interestingly, changes in the NAc often have a different character and intensity compared to the changes observed in the other parts of the basal ganglia, in particular the dorsal striatum. In this review, we highlight the role of the NAc in various pathological processes in the context of its structural and functional damage, impaired connections with the other brain areas cooperating within functional systems, and progression of the pathological processes

Biochemical properties of the HtrA homolog from bacterium Stenotrophomonas maltophilia

The HtrA proteins due to their proteolytic, and in many cases chaperone activity, efficiently counteract consequences of stressful conditions. In the environmental bacterium and nosocomial pathogen Stenotrophomonas maltophilia HtrA (HtrA.Sm) is induced as a part of adaptive response to host temperature (37. \uc2\ub0C).We examined the biochemical properties of HtrA.Smand compared them with those of model HtrA.Ecfrom Escherichia coli. We found that HtrA.Smis a protease and chaperone that operates over a wide range of pH and is highly active at temperatures between 35 and 37. \uc2\ub0C. The temperature-sensitive activity corresponded well with the lower thermal stability of the protein and weaker stability of the oligomer. Interestingly, the enzyme shows slightly different substrate cleavage specificity when compared to other bacterial HtrAs. A computational model of the three-dimensional structure of HtrA.Smindicates differences in the S1 substrate specificity pocket and suggests weaker inter-trimer interactions when compared to HtrA.Ec.The observed features of HtrA.Smsuggest that this protein may play a protective role under stressful conditions acting both as a protease and a chaperone. The optimal temperatures for the protein activity may reflect the evolutionary adaptation of S. maltophilia to life in soil or aqueous environments, where the temperatures are usually much below 37. \uc2\ub0C