Valina L. Dawson

Adult Conditional Knockout of PGC-1α Leads to Loss of Dopamine Neurons

Visual Abstract Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder. Recent studies have implicated a role for peroxisome proliferator-activated receptor γ coactivator protein-1α (PGC-1α) in PD and in animal or cellular models of PD. The role of PGC-1α in the function and survival of substantia nigra pars compacta (SNpc) dopamine neurons is not clear. Here we find that there are four different PGC-1α isoforms expressed in SH-SY5Y cells, and these four isoforms are expressed across subregions of mouse brain. Adult conditional PGC-1α knock-out mice show a significant loss of dopaminergic neurons that is accompanied by a reduction of dopamine in the striatum. In human PD postmortem tissue from the SNpc, there is a reduction of PGC-1α isoforms and mitochondria markers. Our findings suggest that all four isoforms of PGC-1α are required for the proper expression of mitochondrial proteins in SNpc DA neurons and that PGC-1α is essential for SNpc DA neuronal survival, possibly through the maintenance of mitochondrial function.

Chapter 27 – Influence of Nitric Oxide on Neuroendocrine Function and Behavior

Publisher Summary Nitric oxide (NO) functions as a neurotransmitter and neuromodulator in the central and peripheral nervous systems. This chapter describes how the use of pharmacological agents that block synthesis of NO, the use of knockout mice that lack one of the various isoforms of nitric oxide synthase, and neuroanatomical studies have revealed that NO appears to play an important role in the control of several neuroendocrine pathways and behaviors. The effects of NO on blood vessel tone and neuronal function form the basis for an important role of NO on neuroendocrine function and behavior. NO mediates hypothalamic-portal blood flow, and thus, affects neuropeptide secretion, as well as mediates neuroendocrine function in the hypothalamuspituitary-adrenal and the hypothalamuspituitary-gonadal axes. NO influences several motivated behaviors including sexual, aggressive, and ingestive. Learning and memory functions are also influenced by NO. Taken together, NO is emerging as an important chemical mediator of neuroendocrine function and behavior.