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, NF kappa B), 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.

Automated summary

Stress, negative emotions, addictive substances, and metabolic and/or genetic predispositions can negatively impact brain function, specifically the nucleus accumbens (NAc). NAc damage is associated with mental disorders like depression and schizophrenia, as well as neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's. This can be attributed to the breakdown of extensive connections and impairment of neuroplasticity mechanisms. NAc lesions result in both morphological and functional changes, affecting volume, cell number, dendritic structure, synapse number, synaptic transmission efficiency, signaling pathways, and gene expression.